Abstract:
Isolation, cloning and sequencing of the cluster of genes involved in the biosynthesis of the carbapenem thienamycin by  streptomyces cattleya,  and the use of those genes to increase thienamycin production, and/or related antibiotics, in the producing strains, and obtaining new derivatives by means of genetic manipulation which implies gene expression, mutagenesis by gene replacement and combinatorial biosynthesis.

Description:
SUMMARY OF THE INVENTION  
         [0001]    The present invention relates to the cloning and sequencing of the thienamycin biosynthetic gene cluster from  Streptomyces cattleya  and the use of the genes included therein to increase yields of thienamycin, or related antibiotics, in the producer strain/s and to obtain novel derivative compounds by genetic manipulation concerning gene expression, mutagenesis by gene inactivation and combinatorial biosynthesis.  
         FIELD OF THE INVENTION  
         [0002]    The present invention concerns the isolation and identification of a gene cluster involved in the biosynthesis of the carbapenem antibiotic thienamycin by  Streptomyces cattleya  and provides a tool for the genetic manipulation of the cluster in order to increase thienamycin production and to obtain novel derivatives with improved properties.  
         BACKGROUND OF THE INVENTION  
         [0003]    Thienamycin (FIG. 1) is the first β-lactam antibiotic of the carbapenem family that was isolated (Kahan et al., J. Antibiot. v. 23: 1255-1265, 1979). It is one of the most potent and broadest in activity spectrum of all known antibiotics and it has an important clinical use in the treatment of infectious diseases, particularly in hospitals. Thienamycin is active against Gram-positive and Gram-negative pathogenic bacteria, both aerobic and anaerobic (including clinical isolates resistant to classic β-lactam antibiotics) and it is highly resistant to bacterial β-lactamases. It is produced at low level by the wild type strain  Streptomyces cattleya  NRRL 8057, that also produces the convenctional β-lactam antibiotic cephamycin C. Thienamycin is highly unstable and a most stable derivative, named imipenem (N-formidoil thienamycin), is the antibiotic of choice for clinical usage.  
           [0004]    The development of recombinant DNA technology has provided a powerful tool that has contributed to the knowledge of gene clusters involved in antibiotic biosynthesis in many actinomycete species. This technology can now be applied to increase yields of antibiotics in the producer strains and to obtain novel derivative compounds with improved properties by expression of genes from selected biosynthetic pathways through combinatorial biosynthesis. Recombinant DNA technology has made possible the isolation of complete antibiotic biosynthetic gene clusters, using among other screening strategies, the screening of gene libraries with DNA probes. This approach relies on the existence of previous genetic information concerning the pathway or related pathways that could allow the construction of a probe using information from a partial aminoacid sequence of a biosynthetic enzyme.  
           [0005]    Biosynthesis of classic β-lactam antibiotics, as penicillins, cephalosporins and cephamycins is a well known process that takes place by condensation of L-α-aminoadipic acid, L-cysteine and L-valine to form the tripeptide δ-(L-α-aminoadipyl)-L-cysteinyl-D-valine (ACV) by a non-ribosomal peptide synthetase, named ACVS (encoded by the pcbAB gene). Cyclization of this tripeptide is then carried out by isopenicillin N synthase o IPNS (encoded by the pcbC gene). These two steps are common in all producers of convectional β-lactam antibiotics, both bacteria and fungi, and the corresponding genes and enzymes are very well known and are conserved among all producers despite their phylogenetic origin.  
           [0006]    On the other hand, there is biochemical evidence supporting that thienamycin biosynthesis in  Streptomyces cattleya  could proceed through an alternative pathway to the classic β-lactam antibiotic cephamycin C, also produced by this strain (Williamson et al., J. Biol. Chem. v. 260: 4637-4647, 1985). The bicyclic ring in thienamycin derives from acetate β-lactam carbons) and glutamate (pyrrolidine ring) and it has been proposed that it is formed after condensation of acetyl-S-CoA with y-glutamylphosphate instead of the ACV tripeptide formation as occurs in penicillins, cephalosporins and cephamycins biosynthesis (Williamson et al., 1985, supra). From the genetic point of view, there are no previous reports in the literature concerning the sequencing of the thienamycin biosynthetic gene cluster or any other carbapenem antibiotic produced by Streptomyces species.  
           [0007]    A novel mechanism for the biosynthesis of the β-lactam ring, has been reported lately for the biosynthesis of the non classic β-lactams, carbapenems and clavams. These two groups of β-lactam compounds are synthesized by a mechanism never reported in classic β-lactam antibiotic biosynthesis. This alternative mechanism for β-lactam ring biosynthesis involves a novel biosynthetic enzyme, a β-lactam synthetase, that was found to participate first in the biosynthesis of the carbapenem antibiotic (1-carbapen-2-em-3-carboxylic acid) produced by the Gram-negative bacterium  Erwinia carotovora  (now  Pectobacterium carotovorum ), from where the gene cluster was cloned (McGowan et al., Mol Microbiol v. 22: 415-426, 1996; Salmond et al. U.S. Pat. No. US0,058,719,22A, 1999). The same mechanism, involving a β-lactam synthetase, was found to be involved in the biosynthesis of the clavam clavulanic acid and forms part of the gene cluster for this β-lactamase inhibitor in the Gram-positive bacterium  Streptomyces clavuligerus  (Bachmann et al., Proc Nati Acad Sci USA v. 95: 9082-9086, 1998).  
           [0008]    The present invention is directed to the aim of the cloning and sequencing of the thienamycin biosynthetic gene cluster from the producing strain Streptomyces cattleya NRRL 8057. The genetic information available about the biosynthetic enzyme, β-lactam synthetase, has been used to design synthetic oligonucleotides and generate a probe that allowed the cloning of the thienamycin gene cluster from  Streptomyces cattleya.  This is the first instance wherein the gene cluster for producing thienamycin has been isolated. The invention provides as well a tool for the genetic manipulation of the cluster in order to increase thienamycin production and to obtain novel potential derivatives with improved properties. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0009]    [0009]FIG. 1. Structure of the carbapenem antibiotic thienamycin.  
         [0010]    [0010]FIG. 2. Diagram showing a schematic representation of the restriction endonuclease map of the gene cluster for thienamycin biosynthesis of  Streptomyces cattleya  NRRL 8057.  
         [0011]    [0011]FIG. 3. Schematic representation of inserts included in cosmid cosCAT25 and in plasmids pLE14 and pLE22.  
         [0012]    [0012]FIG. 4. Insertional inactivation of ORF6 by gene replacement.  
         [0013]    (A) Construction of the plasmids pHZLE6R and pHZLE6F to be used in the gene inactivation.  
         [0014]    (B) Gene replacement of the  Streptomyces cattleya  wild type strain by insertion of an apramycin resistance cassette in ORF6.  
         [0015]    [0015]FIG. 5. HPLC analysis:  
         [0016]    (A) Thienamycin production in the wild type strain of  Streptomyces cattleya,  with indication of the thienamycin absorption spectrum.  
         [0017]    (B) Thienamycin non producing mutant obtained after inactivation of ORF6 by gene replacement using pHZLE6F.  
         [0018]    (C) Thienamycin non producing mutant obtained after inactivation of ORF6 by gene replacement using pHZLE6R. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0019]    This invention relates to the cloning and sequencing of the gene cluster encoding a β-lactam synthetase involved in the biosynthesis of the carbapenem antibiotic thienamycin. The invention thus relates to novel genes and nucleic acid molecules encoding proteins/polypeptides exhibiting functional activities involved in thienamycin biosynthesis, such proteins/polypeptides themselves, and their uses both in increasing thienamycin production in  Streptomyces cattleya  and in the generation of novel thienamycin derivatives.  
         [0020]    The experimental procedures of the present invention include molecular biology methods conventional in the art. Detailed description of the techniques not explained here are given in the manuals by Hopwood et al. “Genetic manipulation of Streptomyces: a laboratory manual”. The John Innes Foundation, Norwich (1985); by Sambrook et al. “Molecular cloning: a laboratory manual” (1989) and by Kieser et al. “Practical Streptomyces genetics”. The John Innes Foundation, Norwich (2000).  
         [0021]    In order to clone the thienamycin biosynthetic gene cluster, a chromosomal DNA cosmid library from  Streptomyces cattleya  NRRL 8057 was constructed in Escherichia coli, using the bifunctional cosmid pKC505.  
         [0022]    For the isolation of the thienamycin biosynthetic gene cluster we have used information concerning a novel biosynthetic enzyme, β-lactam synthetase, above mentioned, to obtain a genetic probe. The strategy was based in the design of a pair of degenerated oligonucleotides according to the conserved regions between the two available β-lactam synthetase sequences (Bachmann et al., 1998, supra and McGowan et al., 1996, supra) as were deduced from the protein alignment. The synthetic oligonucleotides were BLS1 (5′ ATCGTCTAGACSGASACSTCSAACGAGTTS-3′) and BLS4 (5′-ATCGMGCTTSGASCCCTCGTGGACGCC-3′) and were used in PCR-assisted amplification to obtain a probe from the  S. cattleya  chromosome.  
         [0023]    Three cosmid clones, called cosCAT25, cosCAT22 and cosCAT14, were isolated by hibridization with the amplified probe. One cosmid, cosCAT25 (FIG. 2 and  3 ), was presumed to contain most of the thienamycin gene cluster and was selected for sequencing. In addition two overlapping clones, pLE22 and pLE14, (obtained by subcloning adjacent BamHI fragments from the cosCAT22 and cosCAT14) were further sequenced. Analysis of the nucleotide sequence revealed the presence of 28 complete open reading frames (ORFs) and two incomplete ORFs (FIG. 2 and  3 ), most of them probably involved in thienamycin biosynthesis. The functions of the genes were concluded after comparison of the deduced amino acid sequences with known sequences available in the data bases and will be described herein below. Some of them would encode structural biosynthetic enzymes, transcriptional activators, proteins involved in exportation, quorum sensing, etc. Among the ORFs coding for structural functions it has been found ORF5, whose deduced product is highly homologous to the β-lactam synthetase proteins that were used in the design of the probe (Bachmann et al., 1998, supra and MacGowan et al., 1996, supra). Two ORFs, (ORF2 and ORF12) would encode regulatory proteins, in fact transcriptional activators highly homologous to ClaR and CcaR from  Streptomyces clavuligerus.  ClaR works as a transcriptional activator of clavulanic acid biosynthetic genes (Pérez LLarena et al., J. Bacteriol. v. 179: 2053-2059, 1997; U.S. Pat. No. US0,058,210,77A, 1998) and CcaR activates transcription of both clavulanic acid and cephamycin C biosynthetic genes (Paradkar et al., J. Bacteriol. v. 178:6266-6274, 1998).  
         [0024]    The involvement of this gene cluster in thienamycin biosynthesis has been demostrated by insertional inactivation of one of the ORFs in the middle of the cluster (ORF6 which forms part of the same transcriptional unit than the β-lactam synthetase homologue), through the insertion of an apramycin resistance cassette generating a thienamycin non producing mutant, as was determined by bioassay and HPLC analysis. The strategy followed for this process has been a gene replacement experiment in which the introduction of plasmid DNA into  Streptomyces cattleya  was achieved by using intergeneric conjugation from  Escherichia coli,  according to the method from Mazodier et al., J. Bacteriol. v. 171: 3583-3585 (1989).  
         [0025]    The present invention includes a method for increasing the thienamycin producing ability of  Streptomyces cattleya.  It consists in the overexpression of either (1) regulatory genes from the thienamycin gene cluster, capable of activating gene expression of the cluster, or (2) structural biosynthetic genes, preferably coding for a product that is rate-limiting in the biosynthetic pathway.  
         [0026]    The invention further comprises several procedures for manipulating the biosynthetic genes in order to obtain novel thienamycin derivatives: (1) by gene replacement techniques generating mutants in the late steps in thienamycin biosynthesis which could lead to the accumulation of thienamycin intermediates, and (2) by expression of different set of genes in heterologous hosts (β-lactam producers or non producers) in combinatorial biosynthesis experiments.  
         [0027]    The present invention will be described in more detailed and illustrated herein below through the following non limiting examples.  
       EXAMPLE 1  
       [0028]    Cloning of the Gene Cluster for Thienamycin Biosynthesis  
         [0029]    1.1. Bacterial Strains, Plasmids and Growth Conditions  
         [0030]    Bacterial strains and plasmids used in this study are listed in Table 1.  S. cattleya  NRRL 8057 was cultured for sporulation on solid Bennet medium (Locci et al. J. of Microbiol., v. 17: 1-60, 1969); for antibiotic production was cultured in liquid R5A medium (Fernández et al, J Bacteriol, v. 180: 4929-4937, 1998) using an inoculum previously grown in liquid TSB medium (Merck). Intergeneric conjugation from  E. coli  ET12567 (pUB307) into  S. cattleya  was done according to Mazodier et al. (1989), supra and Flett et al., FEMS Microbial Lett., v. 155: 223-229 (1997).  E. coli  strains were grown and transformed as described in Sambrook et al. (1989), supra.  
                             TABLE 1                           Bacterial strains and Plasmids used in this study            Strain, plasmid   Properties   Source or reference                 E. coli  DH10B   general cloning host   Gibco         E. coil  ED8767   host for the cosmid   Sambrook et al. 1987,           gene library   supra         E. coil  ET12567   strain for intergeneric   MacNeil et al, Gene,           conjugation   v. 111:61-68, 1992         S. aureus      thienamycin sensitive   ATCC       ATCC 6538P         S. cattleya     wild type, thienamycin   Kahan et al, 1979,       NRRL 8057   producer   supra       pBluescript SK     E.coli  cloning vector   Stratagene       pKC505   cosmid for gene   Richardson et al., Gene,           library construction   v. 61:231-241, 1987       pUG18     E. coil  cloning vector   Pharmacia       pHZ1358   cosmid for intergeneric   Sun et al., Microbiology,           conjugation   v.148:361-371, 2002       pUB307   plasmid for   Bennet et al., MGG,           intergeneric   v. 54:205-211, 1977           conjugation                  
 
         [0031]    1.2. Analysis of Thienamycin Production  
         [0032]    Thienamycin production was qualitatively assayed by bioassay against the thienamycin sensitive strain  Staphylococcus aureus  ATCC 6538P (cephamycin C resistant). Thienamycin identification and quantitative analysis was performed by HPLC using a reversed phase column (Symmetry C18, 4.6×250 mm; Waters) with acetonitrile and 0.1% trifluoroacetic acid in water as the mobile phase (5:95), at a flow rate of 1 ml/min. Detection and spectral characterization of peaks were made with a photodiode array detector and Millennium software (Waters), and quantification was done after signal integration at 311 nm.  
         [0033]    1.3. DNA Manipulation  
         [0034]    Plasmid, and total DNA preparations, endonuclease digestions, ligations, etc. were performed as described previously (Sambrook et al., 1989, supra; Kieser et al., 2000, supra; Hopwood et al., 1985, supra). DNA fragments were isolated from agarose gels using the QUIAquick Gel Extraction Kit from QIAGEN (Hilden, Germany) labelled with the use of the DIG DNA Labelling and Detection Kit from Roche Diagnostics (Manheim, Germany) and used for Southern blot analysis according to the manufacturer&#39;s manual. DNA sequencing was performed at QIAGEN GmbH (Germany), and the data were analysed with the GCG software (Devereux et al., Nucleic Acids Res. v. 12: 387-395, 1984).  
         [0035]    1.4. PCR-Assisted Amplification and Cloning of a DNA Fragment Encoding Part of a β-Lactam Synthetase from the  S. Cattleya  NRRL8057 Genome  
         [0036]    The strategy developed for the cloning of the thienamycin gene cluster was the genetic homology with previously known clusters corresponding to pathways for β-lactam biosynthesis. Available genetic information concerning a β-lactam synthetase, a novel biochemical mechanism for β-lactam biosynthesis, was used for this purpose. Thus, in order to obtain the DNA encoding the thienamycin biosynthesis genes, a  S. cattleya  NRRL 8057 cosmid gene library was probed with labelled β-lactam synthetase-encoding DNA.  
         [0037]    To construct the DNA probe for the screening, degenerate oligonucleotide primers were designed according to conserved amino acid regions within known β-lactam synthetases, β-Is from  S. clavuligerus  (Bachmann et al., 1998, supra) and carA from  E. carotovora  (McGowan et al., 1996, supra). The degenerate primers used for amplification corresponded to the conserved regions between the two available β-lactam synthetase sequences, as deduced from the protein alignment, and were designed according to the codon usage table for Streptomyces (Wright &amp; Bibb, Gene, v. 113: 55-56, 1992). The selection of the regions for oligonucleotide design was done avoiding the conserved regions with the related proteins as asparragine synthetase. The synthetic sense nucleotide primer, BLS1, corresponded to the amino acid sequence Thr Asp (Glu) Thr (Leu) Ser Asn Glu Phe and had the sequence 5′- ATCG TCTAG A CG/C GAG/C ACG/C TCG/C AAC GAG TTG/C-3′ (SEQ ID NO: 32), including an Xbal restriction site for cloning (underlined). The antisense nucleotide primer, BLS4, corresponded to the amino acid sequence Gly Val (IIe) His Glu Gly Ser and had the sequence 5′-ATCG AAGCTT  G/CGA G/CCC CTC GTG GAC GCC-3′) (SEQ ID NO: 33), including an HindIII restriction site for cloning (underlined). Total DNA obtained from  S. cattleya  NRRL 8057 cultured on TSB medium (Tryptone Soya Broth, Oxoid) was isolated as described (Kieser et al., 2000, supra). The total genomic DNA from  S. cattleya  NRRL 8057 was further used as a template for polymerase chain reaction (PCR)-assisted amplification of the DNA fragment from the genome of this organism with the use of BLS1 and BLS4 oligonucleotide primers. It was assumed that both oligonucleotides would allow the amplification of an internal fragment of the β-lactam synthetase encoding gene and that the resulting PCR product would be of approx 0.5 kb in size. The PCR reaction was carried out in a total volume of 50 μl and the PCR mixture contained 0.1 μg of  S. cattleya  NRRL 8057 total DNA, 200 pm of each oligonucleotide primer, dNTPs (final concentration of 200 μM), 1×PCR buffer from Taq DNA polymerase and 5U of Taq DNA polymerase (Gibco BRL). The PCR was performed on the MJ Research MiniCycler™ with the following program: 1 cycle of denaturation at 98° C. (5 min), 30 cycles of denaturation/annealing/synthesis at 94° C. (1 min)/65° C. (1min)/72° C. (1 min) and 1 cycle of final extension at 72° C. (5 min). A DNA fragment obtained with this procedure was cloned in the  Escherichia coli  vector pUC18 (using the Xbal/HindIII restriction sites included in the synthetic oligonucleotides) and was subjected to further DNA sequencing using standard techniques in Molecular Biology. DNA sequence analysis of the resulting amplified fragment followed by conceptual translation and database search revealed that the PCR product encoded a region homologous to part of known β-lactam synthetases (Bachmann et al., 1998, supra and McGowan et al., 1996, supra). However, the amplified DNA fragment was shorter than expected initially. In fact it was of 0.22 kb in size, due to the annealing of the BLS1 oligonucleotide to an internal region of the expected in the initial design. Once confirmed that the amplified DNA fragment encodes part of a β-lactam synthetase it was used as a probe for screening a  S. cattleya  NRRL 8057 cosmid gene library (see below).  
         [0038]    1.5. Construction and Screening of the  S. Cattleya  NRRL8057 Gene Library  
         [0039]    The  S. cattleya  NRRL 8057 gene library was constructed in the bifunctional cosmid pKC505 (Richardson et al., Gene, v. 61: 231-241, 1987), which is able of replication both in  Escherichia coli  and Streptomyces. Total DNA from  S. cattleya  NRRL 8057, isolated as described above, was partially digested with Sau3Al and fragments of about 35 kb were dephosphorylated by alkaline phosphatase treatment (Roche Diagnostics, Mannheim). The cosmid vector was linearized with Hpal, dephosphorylated, and digested with BamHI to generate both cosmid arms. Insert DNAs and vector were ligated and packaged in vitro using a commercial packaging kit from Roche Diagnostics Mannheim. The recombinant phage particles were used to infect  E. coli  ED8767 and transductants selected on trypticasein-soy agar (TSA) plates (containing 10 μgml −1  tobramycin). Approximately. 3000 transductants were cultured on microtiter plates and, after incubation at 28° C. for 24 h, kept with 25% glycerol at −70° C.  
         [0040]    In order to clone the gene cluster for thienamycin biosynthesis the genomic library of  S. cattleya  NRRL 8057 was screened by in situ colony hybridization with the amplified probe corresponding to an internal fragment of the β-lactam synthetase encoding gene (see above). For the screening of the cosmid library the DNA probe was labelled with α-P 32  dCTP and hybridization was carried out using the Rediprime DNA labelling system (Amersham) according to the manufacturer&#39;s manual. Three hybridising cosmid clones, cosCAT25, cosCAT22 and cosCAT14, were isolated and selected for further analysis. After Southern blot analysis using the same probe it was determined that the three cosmids show overlapping restriction maps and one of them, cosCAT25 (FIG. 2 and  3 ), was selected for sequencing analysis. In addition, two overlapping clones, pLE22 and pLE14 (FIG. 2 and  3 ), obtained after subcloning adjacent BamHI fragments from the cosCAT22 and cosCAT14, were also sequenced.  
       EXAMPLE 2  
       [0041]    Sequence Analysis of the Gene Cluster for Thienamycin Biosynthesis and the Deduced Functions from the Genes  
         [0042]    Sequence analyses were made using the GCG sequence analysis software package (Version 8: Genetics Computer Group, Madison, Wis., USA). The translation table was modified to accept also GTG as a start codon. Codon usage was analyzed using published data (Wright and Bibb, 1992, supra)  
         [0043]    Computer-assisted analysis of the DNA sequence (FIG. 2) comprised the region cloned in cosmid cosCAT25 (26571 bp) and the two overlapping BamHI fragments from cosmids cosCAT22 and cosCAT14 that were cloned in pLE14 (4806 bp) and pLE22 (6144 bp) (FIG. 3). According to the CODONPREFERENCE program the sequenced DNA fragment revealed 28 complete open reading frames (ORFs) and two 5′ ends of the other ORFs (ORFX and ORFW5). The functions of the genes were concluded by comparing the amino acid sequences translated from their base sequences to the known sequences in the data banks. The results are shown in Table 2 referring to the sequence data given in the application.  
                                                     TABLE 2                               A-                       mino               Gene   Position   acids   Deduced function   Remarks                                orfX    −751   &gt;250   unknown   not complete           compl           SegID.NO:2       orfX1    1034-1924   296   unknown   SegID.NO:3       orfZ    1940-2719   259   putative   SeqID.NO:4           compl       oxidoreductase       orfZ1    2850-3932   360   putative   SeqIDNO:5           compl       efflux pump regulador       orfZ2    4117-4755   212   putative   SeqID.NO:6                   efflux protein                   LysE family       orfZ3    4945-6036   363   putative   SegID.NO:7                   oxidoreductase       orf1    6288-7172   294   enoyl-CoA   SeqID.NO:8                   hydratase                   CarB homologue       orf1b    7156-8139   327   unknown   SeqID.NO:9           compl       orf1c    8136-8927   263   putative   SeqID.NO:10           compl       hydroxylase       orfA    9171-9845   224   putative epoxide   SeqID.NO:11                   hydrolase       orf2    9767-11197   476   putative transcriptional   SeqlD.NO:12           compl       activator ClaR                   homologue       orf2c   11289-12740   483   putative transport   SeqID.NO:13           compl       protein       orf3   12737-14782   681   putative   SeqID.NO:14           compl       methyltransferase       orf4   14838-16262   474   putative   SeqID.NO:15           compl       methyltransferase       orf5   16234-17610   458   putative β-lactam   SeqID.NO:16           compl       synthetase       orf6   17612-18715   367   unknown   SeqID.NO:17           compl.       orf7   18754-20172   472   unknown   SeqID.NO:18           compl       orf8   20169-21623   484   putative   SeqID.NO:19           compl       methyltransferase       orf8d   22038-22817   259   unknown   SeqID.NO:20       orf9   22912-23634   240   unknown   SeqID.NO:21           compl       orf10   23744-24733   329   unknown   SeqID.NO:22       orf11   24784-25983   399   unknown   SeqID.NO:23       orf12   26146-26952   268   transcriptional   SeqID.NO:24                   activator                   CcaR homologue       orf13   26980-27393   137   unknown   SeqID.NO:25           compl       orfY   27614-28156   180   unknown   SeqID.NO:26           compl       orfW1   28224-28412   62   unknown   SeqID.NO:27       orfW2   28485-29246   253   unknown   SeqID.NO:28       orfW3   29382-29567   61   unknown   SeqID.NO:29       orfW4   29766-30197   143   unknown   SeqID.NO:30       orfW5   30695-   &gt;545   unknown   not complete                       SeqID.NO:31                  
 
       EXAMPLE 3  
       [0044]    Insertional Inactivation of the Thienamycin Gene Cluster by Gene Replacement  
         [0045]    In order to demonstrate the involvement of the cloned gene cluster in thienamycin biosynthesis, ORF6, immediately upstream of the β-lactam synthetase homologue (ORF5) was inactivated by insertion of an apramycin resistance cassette containing the aac(3)IV gene (Stanzak et al. Biotechnology v. 4: 229-232, 1986). For insertional inactivation of chromosomal genes in Streptomyces the gene inactivation is usually created on a suitable vector in  E. coli  before introducing the construct into Streptomyces for recombination with the chromosome. For this purpose, a 8.4 kb DNA BamHI fragment from cosmid cosCAT25 was first cloned into the pUC18 vector in  E. coli,  resulting in the plasmid pLESC6 (FIG. 4A). In this later construction, an apramycin resistance cassette was independently inserted in both orientations in the unique Bg/II restriction site (blunt ended) localized in the ORF6 coding region, generating pLE6F (with the apramycin cassette in forward orientation) and pLE6R (with the apramycin cassette in reverse orientation). From these two constructions in which ORF6 was insertional inactivated by the apramycin resistance cassette, the 9.9 kb DNA BamHI fragment was excised and ligated to the conjugative vector pHZ1358, previously digested with the same restriction enzyme, generating pHZLE6F and pHLE6R (FIG. 4A).  
         [0046]    The recombinant plasmids constructed for the gene replacement experiments (pHZLE6F and pHZLE6C) were introduced into  S. cattleya  by intergenic conjugation from  E. coli  ET12567 (pUB307) as described by Mazodier et al. (1989), supra. A double crossover is necessary to obtain the replacement of the wild type copy of the gene by the mutated one. The transconjugants in which a double crossover event has happened were selected for apramycin resistance and thiostrepton sensitivity. Replacement in the chromosome of the wild type copy of the gene by the mutated one was confirmed in the transconjugants by Southern blot analysis with the use of labelled 8.4 kb BamHI fragment from plasmid pLESC6 (FIG. 4B). One of each replaced mutant (with apramycin gene inserted in different orientation) was tested for thienamycin production in parallel with the parental strain NRRL 8057 by bioassay and HPLC (see above for methods under “analysis of thienamycin production”). Both mutants, with independence of the apramycin gene orientation, were shown to be non producers of thienamycin (FIG. 5), confirming the involvement of the cluster in thienamycin biosynthesis.  
         [0047]    Deposited Microorganisms  
                                       Microorganism   Accession number   Date of deposit                     E. coli  ED8767/cosCAT25   CECT 5877   March 7 th  2002         E. coli  DH10B/pLE14   CECT 5876   March 7 th  2002         E. coli  DH10B/pLE22   CECT 5875   March 7 th  2002                  
 
         [0048]    [0048] 
     
       
       
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                                                SEQUENCE LISTING  
               
               
                   
               
               
                   
               
               
                 &lt;160&gt; NUMBER OF SEQ ID NOS: 33  
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 1  
               
               
                 &lt;211&gt; LENGTH: 32329  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                 &lt;300&gt; PUBLICATION INFORMATION:  
               
               
                 &lt;301&gt; AUTHORS: Nunez, Luz Elena  
               
               
                       Mendez, Carmen  
               
               
                       Brana, Alfredo F.  
               
               
                       Blanco, Gloria  
               
               
                       Salas, Jose A.  
               
               
                 &lt;302&gt; TITLE: The Biosynthetic Gene Cluster for the ??Lactam  
               
               
                       Carbapenem Thienamycin in Streptomyces cattleya  
               
               
                 &lt;303&gt; JOURNAL: Chemistry and Biology  
               
               
                 &lt;304&gt; VOLUME: 10  
               
               
                 &lt;306&gt; PAGES: 301-311  
               
               
                 &lt;307&gt; DATE: 2003-04-21  
               
               
                 &lt;308&gt; DATABASE ACCESSION NUMBER: AJ421798  
               
               
                 &lt;309&gt; DATABASE ENTRY DATE: 2001-12-11  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 1  
               
               
                   
               
               
                 ggatccgcgc ggcggcccgg gcgggcacct cggtgcgcca ggcacgggcg atctccggcc     60  
               
               
                   
               
               
                 gcgcgagcac cgccttgagc agggcgtaca gcggtgagcg cggcggggcg gcgcgcaggt    120  
               
               
                   
               
               
                 cgtcggagat ctcgcacagc agcggcacca gccacccctc gtaccagtcg gccagcagcc    180  
               
               
                   
               
               
                 gcggggcgtc ggggtggagg cagatgaatc gggccaggtt ctcccggggt atggcctcgg    240  
               
               
                   
               
               
                 gcacccgggc gacgccggag aagagccggg tgtaggcggc gttgcaggcc agcagccgcc    300  
               
               
                   
               
               
                 aggcggggtc gcgcaggtag gcgggcatcc cgacgtcccg gaagccgcgg tgccattcgc    360  
               
               
                   
               
               
                 gggcgaagcc ggccgggtcg ccggggtgcg gggtctcggg ggcgggggcc gggcgggcgg    420  
               
               
                   
               
               
                 cgggggtacg ggaaccggcc agcccggcca gttcccgctc ctcctcgcgg gtgagggcga    480  
               
               
                   
               
               
                 gggcggcggc gaggtcggcg acgcggcgcg ggtccacgcc gtgctgtccg cgttcccagt    540  
               
               
                   
               
               
                 tgctgaccgt gcgtgtgctg acgtccagcc gccaggccag cccttcctgg ctgagtcctg    600  
               
               
                   
               
               
                 agcgcagtcg gcgggcgcgc aggaacgccg ggagcgggtg gccggccgac ggcccgccgg    660  
               
               
                   
               
               
                 gcggggcggc gcggtcgggg cggcggtcgg ccggccggtg ccgcgctccg ccgccgcggt    720  
               
               
                   
               
               
                 cgccgagggc ggggaacgaa cgtggaatca tgtgcggtac gccttgtcga agccgatcgg    780  
               
               
                   
               
               
                 acggtgacgg gtcacggacg gtcacggagg aggtggccgg ggcgcgacct ggcgccggcc    840  
               
               
                   
               
               
                 cccgtcacgg acgtggcgcc gtgctgtcgc cgccgtcggt gaccaggccg gactcccccg    900  
               
               
                   
               
               
                 gctcgacctg gtacgggcac cgattgtggc cgttgtggcg ggggttgggg agagaagcga    960  
               
               
                   
               
               
                 tttccacgga cgtccgatcc ctattattca cctttcacca accggcccgc cggtttctgt   1020  
               
               
                   
               
               
                 tctggatgga gacatgaccg acgcgcaacc ttccggcccc gtcgtggagc acggacgcgg   1080  
               
               
                   
               
               
                 agacctcacc gccgaggagc ggcgccagaa gctgtccttc ctgcgcgaga agcgcgacag   1140  
               
               
                   
               
               
                 cgtcgaccgg tcctccttcg aggcccgcta ccccgtcgag gtgccacggc ggctccccgg   1200  
               
               
                   
               
               
                 ccggggccgc cacgcccccg ggctcaccct ggtcgagatg ggccgcctgc tcggcctgcg   1260  
               
               
                   
               
               
                 ggacggctcg tggtacgcgg acctggagcg cggccaggtg gacaacgccc cggtggaccg   1320  
               
               
                   
               
               
                 gctgttcaag gtcgccgagc tactggacct gacgcctcgt cagtacgagt tcctgtgcgt   1380  
               
               
                   
               
               
                 gtacgcctgc cggcccaagc ccggttaccc ggcggccggg ctccccggcg gctaccggga   1440  
               
               
                   
               
               
                 ggtgctcgac ctgtaccagg ggccggcgta cttccaggac gccgggtgga acctgctcag   1500  
               
               
                   
               
               
                 gccgaagatg tacaacgcgg cggccgaagc gctcttcaac ggcatccccg acgacttcaa   1560  
               
               
                   
               
               
                 cttcatccgc tgggtgctgc tggaacggtc ggtgcgccgg ccccccgagg gcggccggcg   1620  
               
               
                   
               
               
                 ccacgcctgg ctgccggact tctggcaggt gtgggcgccg cgcgcgctgc cggtggtacg   1680  
               
               
                   
               
               
                 ggccgcgtac gtcgcccggc cggacaacgc caccctcgcc cggctccacg ccgacctggc   1740  
               
               
                   
               
               
                 ggccgacccc gagatcggcc ccatctacca gggccgtctg ccgccctacc cgcacaccga   1800  
               
               
                   
               
               
                 cggcgacctg cgtccgttcg tccacggcag caccggggaa cgcggcatgg tgcggatcaa   1860  
               
               
                   
               
               
                 cgtcctcacc ccgcgcggca gcgacgacac cctgatgctg ctcaactggc accccggcgc   1920  
               
               
                   
               
               
                 ctgacaccgg gcacatccct cagacggtct tgagcgcgcc gccgtcgatc acgtagtcgg   1980  
               
               
                   
               
               
                 cgccgtggac gctggccgcc aggtcggacc cgaggaaggc gatcaggtcg gccacctcgc   2040  
               
               
                   
               
               
                 ccggttcgac cagccggccg gtcaactggc cggagcgggc gggcactcgg gccacgtagt   2100  
               
               
                   
               
               
                 cggccagctc ctggccgccg agggcggcct gctgggcgcc gtagccgtcc gggtcctccc   2160  
               
               
                   
               
               
                 acaccggggt gcgggtgggc cccggcgaga cggtgttgac ccggaccccg cgcggcccga   2220  
               
               
                   
               
               
                 actcggcggc gagcgccttg cccagggtgt tgagcgcggc cttggcggtg gcgtagtcga   2280  
               
               
                   
               
               
                 tcggcccggt ggcgttgcgg gcgccgatcg aggagacgtt gacgatcgcg ccgcgccgct   2340  
               
               
                   
               
               
                 cgatcaggga gggcagggcg gcccggatca ggcgtaccgg ggcgaagaag ttgagcgccc   2400  
               
               
                   
               
               
                 aggagcgttc ccagatctcg tcgtcggcgg tgaggaaccc ggccgccgtg aagtggtcgc   2460  
               
               
                   
               
               
                 cgccaccggc gttgttgacc agcaggtcga tcccgcccag ttcggccagg gcacgctgga   2520  
               
               
                   
               
               
                 ccagctccgc gcagccctcg ggggtgctga ggtcgaccgc caccggaacc gcgccggcgt   2580  
               
               
                   
               
               
                 ccttcaactc cgcggtgacg gtccgcgcgg cgcccaccac ccggaccccc tcgccggtca   2640  
               
               
                   
               
               
                 gcgtccgtac caccgccagc ccgatccccc ggctcgcacc ggtcaccaca gcggtcttcc   2700  
               
               
                   
               
               
                 ccgacatccg caggtccatc gtgtcctctc ggtagcaact gctcccgcca cgctatacgc   2760  
               
               
                   
               
               
                 acccgggccg cgtcccggtc ggcgcgcggt ggccggtaac cgccgttcat gcaagggggt   2820  
               
               
                   
               
               
                 ttcatgatgc cgcccggacg cgacgtgcct cagccgcgcc ggggcgtggc ggccaccgcc   2880  
               
               
                   
               
               
                 cgggcggcgc cggggccttg ggcccgggcg gtgacgcggg cggaggccag gcggatcgcg   2940  
               
               
                   
               
               
                 gtttcggtgc ggtcgtcgac ggcggggacg ccggccgcgg cggcgaaggc gccggagggg   3000  
               
               
                   
               
               
                 tcgtggacca cgcggagcgg gggccgggcc gacgctggga aggcctggcg caggcagccg   3060  
               
               
                   
               
               
                 cagagttcgg cgacggacag ccgggcgagg gcgccgagtt cgccggggtc ggcggtgacg   3120  
               
               
                   
               
               
                 agtacggcgg tgaccggggt gtccggcggc gcggcgcgta ccgcatcctc ggcggcctcc   3180  
               
               
                   
               
               
                 agccggtgca gtccgaggac ggtgaccacc tggtccggtt cgccgtccgc cgggaggggg   3240  
               
               
                   
               
               
                 tcgccggtga ccgcgtcggt cgcgggcggc ggggaccacg gttcgtcgac gtggtggacg   3300  
               
               
                   
               
               
                 ggcggcaggc cgggcgcggg cggcgggtcg tcgtccagtg gcaggccggc caggcgctcg   3360  
               
               
                   
               
               
                 cagacccgta cggcgtcgag cgggtcgagg aaaccgggcg cggcggcggc cagttgggcg   3420  
               
               
                   
               
               
                 gtgccgtgca gtgcggtgag gacggcctcg gcgacgcgga ccatgcggcg ggcggggcgt   3480  
               
               
                   
               
               
                 ccggcgggct ccagccgttc cagcgcgagg ccgagcagga tcgcgtcgag cttcagcagc   3540  
               
               
                   
               
               
                 tgggcgaagg gccggcgggt ggcggcgtcg gtgatcacct cgggcatcag gtccatggcg   3600  
               
               
                   
               
               
                 agccgggccg ggccggggcc gtcgtccccg gcgggcggca gccgcgagac ccaggcccgg   3660  
               
               
                   
               
               
                 gcgaacgcgg ccagggcgtc gccgccggag cgcaccggtc gcggcggtgg tccctccggc   3720  
               
               
                   
               
               
                 acgcgttcgg caagcgcggc cagcacggcg aagtagagcg cccgcttgcc ggggaagttg   3780  
               
               
                   
               
               
                 gagtagaccg caccacgggt gagcccggcg cgctcggcga tggcgtcgat cctggcgtcc   3840  
               
               
                   
               
               
                 cggtagccgc gttcggcgaa ctcctcgcgg gcggcgtcca acaccttgtc gcggttgcgt   3900  
               
               
                   
               
               
                 tcctgggtct ccgccctggt cagccgggcc atcgtcctcc tcgccacggg gccgggcacg   3960  
               
               
                   
               
               
                 gtcggccacg gccggttcgc cggtgacggc cggcgccggg aaagcgcttg ccacgcgccc   4020  
               
               
                   
               
               
                 ctggtcacca tatcgccgcg ttccccgcgc acgcggggcg gccgggggcg cgggtggcgg   4080  
               
               
                   
               
               
                 caatcccgtg gacaccgtgc gctcgcgcgc cccacgatgg agcccatgct caccaccgca   4140  
               
               
                   
               
               
                 ctcgcgttcc tcggcgcctg cgtgctgatc gccgccgcgc ccggtcccag cacgatgctc   4200  
               
               
                   
               
               
                 atcatccgcc agtcgctgca cagcagacgg gccggtttcc tgaccgttct gggcaacgag   4260  
               
               
                   
               
               
                 accggggtgc tcacctgggg cgtggtggcg gcgctcgggc tgaccgcgct gctggccgcc   4320  
               
               
                   
               
               
                 tcccgcacgg cgtacgacgt gatgcggatc ggcggggcgg tggtgctggt gtggtacggc   4380  
               
               
                   
               
               
                 gtgcagacgc tgcgggccgc gcggcgcggc gaggcacggc cctccgccgc cgacgacgag   4440  
               
               
                   
               
               
                 gcggcggtgg tgccccgttc cggctggaag atctaccggt ccgggctgct gctcaacctc   4500  
               
               
                   
               
               
                 gccaacccca aggcggccgt cttcgccatg tccttcctgc cgcagttcgt cccggccggt   4560  
               
               
                   
               
               
                 gcgcccaagc tgccggtgat caccgcgctc gccgcgttcc aggcgctctt cgaggtcggg   4620  
               
               
                   
               
               
                 tactacggga tgtacgtgtg gttcgtcggc cggatgaaga gggtgatctc ccgggcgggc   4680  
               
               
                   
               
               
                 gtgcggcgcc ggctggagca ggtgtcgggg ggcgtgctgg tgctgctggg catccggatg   4740  
               
               
                   
               
               
                 gcggtcgaga gctgacgtag cgtcagctac ccggtaggcc cggcgcgtgc ggcgcgtcac   4800  
               
               
                   
               
               
                 ggatccgtgc ggcgccgccc ggcccggcgt tcgcccccgc cgccgccccg aacaccacca   4860  
               
               
                   
               
               
                 caccaccgga cccgtaccgc tgaccgggta ccggcggcgg gcataccggg acgggggacg   4920  
               
               
                   
               
               
                 agggctaccg aggcgggtga cggcgtgacg cttcccaccg agacctgggc ggtgcggatc   4980  
               
               
                   
               
               
                 caccggcacg gcgggccgga ggtgctcgtc cacgaacggc tgccgttgcc gccgctcggc   5040  
               
               
                   
               
               
                 ccggccgacg tcctggtcgc cgtcgacacc gcctcggtct ccggctggga cgtgaagtac   5100  
               
               
                   
               
               
                 cggcgcggac tgccgccggg tgcgcggctg cccggccggg aacggtaccg gctgccgctg   5160  
               
               
                   
               
               
                 caactcggcc gcgaggcggc ggggacggtg ctcgccaccg ggccggaggc ggccggccgc   5220  
               
               
                   
               
               
                 ttccgccccg gagaccgggt ggtcgccgtc gtccacccgg agaacccgcg cgccccggag   5280  
               
               
                   
               
               
                 accgtacgcg gcctgggaaa cctctccacc ggcatcgccc tccccggcca ccaggcgccg   5340  
               
               
                   
               
               
                 ggcggctacg cacgctacct gatctgccat caggacatgt ggctgccctt gccgtccggc   5400  
               
               
                   
               
               
                 gtcgacctcg aacaggccgc cgtgacgctg tggccgtacg cgacctgcca ccgcgtactg   5460  
               
               
                   
               
               
                 cgcgaccggt tgcgggtggc gctcggcgag acgctgctgg tgtgcggcgc caccggggcg   5520  
               
               
                   
               
               
                 atggggctgg cggcgctgcg actggcccgg ctgaccgggg tgcgggtgat cgcgatgacc   5580  
               
               
                   
               
               
                 cgctaccggg ccaaggagcg ggcgttgcgg acggccggcg cggacgaggt ggtggtcgcc   5640  
               
               
                   
               
               
                 ggtgatccgc ggcaggcgtg cgaggcggtg cgcgcgctca ccggcgggga aggcgtggac   5700  
               
               
                   
               
               
                 cacgcggtgg acttcaccgg cagcgccgcg ctgctgcggc tggccgtcga ctcgctgcgc   5760  
               
               
                   
               
               
                 ctcggcggcc ggctgtgccc ggccgccacc cagcgtccgc ccggcccgct cccggtgacc   5820  
               
               
                   
               
               
                 accggtgacc tcacccggct ggagatcacc gtgtacggca tccgcggcgc ccgccaccgg   5880  
               
               
                   
               
               
                 gacgcgctgc gggtgctcgc cctgctgggc gacggcagcc tgccggccac cccgatcgcc   5940  
               
               
                   
               
               
                 gcccgcttcc cgctgtcccg ggccggcgcc gcccacgagt tcctggaaca caacaccacg   6000  
               
               
                   
               
               
                 gctgtcggcc gcgtggtgct caaacccggc tggtgaccga cgcgacccgc cgccggccgc   6060  
               
               
                   
               
               
                 cccgggcggc gtaccggccc gccggattcc gggcgggacc tcgggcgtcg gccgggaata   6120  
               
               
                   
               
               
                 tgcgcgtgat cagcgttgac tgccctgtgc acgctaccta ggctctgctc agaacacagc   6180  
               
               
                   
               
               
                 acccgggcac cggcgcggac agcggccctt cgacgacacg acacgactgg cgccgggcgc   6240  
               
               
                   
               
               
                 acggcagttg gtccccggcg gagcggacgg aacggcgaat cggcgcgatg ggcgcggccg   6300  
               
               
                   
               
               
                 ccggcgagcg gagaaccctc tcacggaaaa gaggcacgac cgtggatgtc ccagtgaagc   6360  
               
               
                   
               
               
                 aggagtcgcg gcaggaccgg ttcgaggatc aggacgagga ccggttcgcg gcgcaggagt   6420  
               
               
                   
               
               
                 ccatcgagtg ctcgcggctc ggcgacggga tcgccctggc ggagttctcg ggggcgcacg   6480  
               
               
                   
               
               
                 agcagaaccc gttcagccgc gcgcggatgc gcgaactcac cgcgttgatg cgggagttgg   6540  
               
               
                   
               
               
                 acgcggacga gaaggtcagg tgcgtggtgc tgtacggcgg cgccgggcgg tcgttcgggg   6600  
               
               
                   
               
               
                 tggggggcga cttccacgag gtgtcggagt tcaccggcgg ggacgaggtc aacgcgtgga   6660  
               
               
                   
               
               
                 tcgacgacat caccgacctg tacaccacgg tggcggcaat ctccaagccg gtgatcgccg   6720  
               
               
                   
               
               
                 ccatcgacgg ttatgccatc ggtgtcgggt tgcagatctc gttgtgttgt gactaccggc   6780  
               
               
                   
               
               
                 tcggcagtga gcaggcacgg ctggtgatgc cggagttccg ggtgggcatc gcctgcaact   6840  
               
               
                   
               
               
                 tcggcggttt catgctggag gccgcggccg gccgcaccgt gatgcagcgc atgctgctga   6900  
               
               
                   
               
               
                 cctgcgacga gtggccggcc gaacgggcgc tggcggacgg gctgctgcac gagacggtgg   6960  
               
               
                   
               
               
                 cctcgccccg gctgctggac cgggccctgg agctggcccg gaccatctcc ggctacaccg   7020  
               
               
                   
               
               
                 ccgaggccgt gcagtccacc cgtccgcggg tcaacgcgcc tttcgtggcc gggctggagc   7080  
               
               
                   
               
               
                 ggatccgccg cgaggcgaag gagtcgcacc gcagagcctt cgcggccggc gaggcccagg   7140  
               
               
                   
               
               
                 tgcggatgcg ccgcgtcatc gggcggagct gacctccccg gcgggcgcgg gggtcgcggt   7200  
               
               
                   
               
               
                 cacccggtac gcgtagtcgt agaaccgcga ctcctcgcgc cacccggtcg cccggtacag   7260  
               
               
                   
               
               
                 ggcgagcccg gcccggttgc cggtgtccac ggtgagcacc atctcgccac ggccgcgggc   7320  
               
               
                   
               
               
                 ccgggccgcg gccatcaccg accgcagcag gaaggcaccg aggcgccgac cgcgcatccg   7380  
               
               
                   
               
               
                 cggcagcacg ccgatctgcc gcaggtaggc ggcgccccgg gtctgcgcca tgcggtcggt   7440  
               
               
                   
               
               
                 gacgttggcg aaccccaccg gctcgccgtc gagttcgagc agcgcgcgct gggacggatc   7500  
               
               
                   
               
               
                 ggcccccggg tcggcgccgg tccagcgcag ccactcctcg aagccgtccg gctccatgcc   7560  
               
               
                   
               
               
                 ggcctcctcg gcggagaagg cacggttctt caccgcgtgg aaggcccgca gccccgcctc   7620  
               
               
                   
               
               
                 accctccggc acccgcacca ccgccccggg caccgggggc tcccccgccg tcgccccgcc   7680  
               
               
                   
               
               
                 cagcggcacc gacatccgca ggtacggacg cggggcggcg aacccgtagg cgctgagcgc   7740  
               
               
                   
               
               
                 gatccgcagc gcggtctccc gttccgacac gaaacacgac agacacacct cgccttcggg   7800  
               
               
                   
               
               
                 ccgcccggcc gcgatggtcc ggcagcggcg gtgggcgaag tcgagcagtg aggcggcgtc   7860  
               
               
                   
               
               
                 gtcgggggtg gcgtgcgggg cgagcaggag ttcggcgtcc caggcggagc gccccgagga   7920  
               
               
                   
               
               
                 gcggctgagc cacaccgcgc cggccacctg tccgtcggag ccggtgagca gcgcggtgtc   7980  
               
               
                   
               
               
                 gtgttccggg tcgagccccg gggcggccag ccggccggcg atccaggtgg caccgacctc   8040  
               
               
                   
               
               
                 cacccggccg agcgcggcgc ggtcgcggtc ggcggccagc cggaccaggg cgggcagatg   8100  
               
               
                   
               
               
                 gtctgcgggg cgtatcggga ccagccgccg tgggctcacc gtccgctctc cggcccggcg   8160  
               
               
                   
               
               
                 gggtggcggg gcagcgaata gcagtaggag acggcacgcc ggtcgtcctc ggtggtgttg   8220  
               
               
                   
               
               
                 ggcgccgagg tgtgggcgac gtagccgttg aacagcagcg ccgagccggc cttgcggggc   8280  
               
               
                   
               
               
                 agggtgaccg gggtgaggcc gggccagatg cgtgcgatgt ccagggacgg ttcgcgcggt   8340  
               
               
                   
               
               
                 gaggcgaaga tgtcgccggg gtcgatgccg tccggttcgt agagtttgcg ttcccggtgg   8400  
               
               
                   
               
               
                 gagccgggca ggaagcgcag gcagccgttg tcctcgcggg cgtcgtccac cgcgatccag   8460  
               
               
                   
               
               
                 atggtgtaga cgtccacgta cttctcgtgc cactcgtcgg ccaggaagat ggcgtcctgg   8520  
               
               
                   
               
               
                 tgccagggtt tctgggagcc gacccgggag ggcttggccc acaggaagca gtcgtagaag   8580  
               
               
                   
               
               
                 tcaccgggca ggccgtgcag cggttcgatc agcttctcgt tgaggccgac gaggtcgggg   8640  
               
               
                   
               
               
                 acggcggcga ggtcggcgga gtgttcgtgg gcgcggccga tgatgcgcac cttgccgggt   8700  
               
               
                   
               
               
                 atgcactcct tgccggccgc ccgggcggcc catccgccgc cctccccctc ggcctccagc   8760  
               
               
                   
               
               
                 tgccattcct cggtgctgat gcgcatccgc tcggtgcggc cgatcagttc ggcgcagccg   8820  
               
               
                   
               
               
                 cggcgcatca cctcgagtac ggattcgggc accaggtcgt ccagcgccac gacaccgtcg   8880  
               
               
                   
               
               
                 cgccgcagtt cgtcggacag ggcctggatc gactgggtca ccggcatggg ttccacctct   8940  
               
               
                   
               
               
                 tccggagaac acaaggccag ccgtgctgcc ttggtagatc cctgatcgcc acaactatcc   9000  
               
               
                   
               
               
                 ggtggcggcc gagggggagg caacgcgccg cccgcagatg agtcgggggt cggccaaaaa   9060  
               
               
                   
               
               
                 ggcatagcgc gcggcgctgc cgtccgggcc ggtctcactt acgctgatga cccgtcatgt   9120  
               
               
                   
               
               
                 ggggacaagg accgacccgg gaaccgggcg gcgacaaccg gggtgtgccg atggtgtgtg   9180  
               
               
                   
               
               
                 cagcgtccag tccggcgggc gccctgctgg tcgactgggg cggtgtgctg acccagccgt   9240  
               
               
                   
               
               
                 tctacgccgg gatcgccgag tgggccgcgc gggacggggt ggacgccgac gccttccacg   9300  
               
               
                   
               
               
                 cgttgctggc ccggcacctc ggtccgggtg cgcccggtgg cgcggcggcc tccgtcttcc   9360  
               
               
                   
               
               
                 accgggtgga gcgcggtgag gtgccggtgg ccgagctgga ggtgacgctg gcggagtcgc   9420  
               
               
                   
               
               
                 tgcgccgccc ggacggcacc gggccgcccg ccgaggggct gatccagcgc atgttccagc   9480  
               
               
                   
               
               
                 cgttcaccat ggccggcgcc atggtggagc tggtgcgccg ggtgcgcgcc tcgggggcgg   9540  
               
               
                   
               
               
                 cggtggcgtt gctctccaac tcctggggcc acacctacga ccgcaccggc tgggacggcc   9600  
               
               
                   
               
               
                 tcttcgacga ggtggtcatc tcctgcgagg tggggatgcg caagccggag ccggagatct   9660  
               
               
                   
               
               
                 accggtacac cgcgcggcgg ctcggggtgg cgccgcggcg gtgtgtcttc ctggacgatc   9720  
               
               
                   
               
               
                 tgggacgcaa cgtgcgggcc gcggcggcgg tggggatgac cgccgttcag cacacctcgg   9780  
               
               
                   
               
               
                 tggaggagag cagcagggag ctggcccggt tcttcgacgt ctcgccgctg ccggccgggc   9840  
               
               
                   
               
               
                 gttgacgggg caggggtggc gtggtgctcg ccgcggcccg gcgcagcgcg gcgacgaggg   9900  
               
               
                   
               
               
                 tgtcgagccg gtcctcggcg gcctcggtgc agtgcagcag ccggcgggcc atgggggaaa   9960  
               
               
                   
               
               
                 ggcaggtgcc gcggggtgcg ctgtgcacca gggtgcgtcc gcagacctgt tccaggcggt  10020  
               
               
                   
               
               
                 ggatgcgccg ggtgagggcg ggttgggtga tcagcaggtc ggacgcggcg cggttgaggc  10080  
               
               
                   
               
               
                 tgccggtgcg ttcgatgacc cgcagcaggt agaggtgttc cgcctcgacc agcgaggagg  10140  
               
               
                   
               
               
                 ggccctcggc cgtccagtgg cgttcgcaga ccaggaacgg cagcgggtcg cgggggccgt  10200  
               
               
                   
               
               
                 cgggctcggt ggcggcggac cggccaggcg gcggcgccga caggtcagcg gcgggtaacg  10260  
               
               
                   
               
               
                 ggaaggtggt ggagcgcaga tagccggggt tgcgttcggc agcgtgctgg acgtagcgcc  10320  
               
               
                   
               
               
                 gctgcagccc ggtacacagg tcacgggcga gcgcctcggg cagcagcagc ggatcggtgg  10380  
               
               
                   
               
               
                 cgaggaagag gcggcgcacg acctgctggc gcagcgggcg cagcgcgtac ccggcgtcct  10440  
               
               
                   
               
               
                 cgaccggggc cgcgcacagc ggggagacca gggcgaagcc gtagccgcgt gccaccaggt  10500  
               
               
                   
               
               
                 cggcggcggc gctgcgggag tggacggtgc agccgacgcg tggggtgagc ccgtgccggg  10560  
               
               
                   
               
               
                 cgaaggcacg ggccaggtcc tcgtgggtgg actcgcccac gatggcgacc cattcggcct  10620  
               
               
                   
               
               
                 cggcgaggtc ctccaggccg agggcgccgc ggccggcgag gggatggccg cggggcaccg  10680  
               
               
                   
               
               
                 ccacccattg cggctcctcg acgaccaggc gcacgtcggc gccgtagcgt cgcagcgccg  10740  
               
               
                   
               
               
                 gggtggagcg ggcccaaccg caggcggcgt ccacggcgta gcggtcgaag cgcgaccaca  10800  
               
               
                   
               
               
                 cgtcctggcg ggcggcgggc accaggtcga agacgacgtc ggggaagccg accgccggct  10860  
               
               
                   
               
               
                 cctcaccggc ctcgcaggtg tattcggtgg agacggccat ctgcaggacg cgcagtcgcg  10920  
               
               
                   
               
               
                 ggccgggttc gtcggtgtcg gcggcgttgg ccatggcgaa gtcgatggcg ccgagcaggc  10980  
               
               
                   
               
               
                 gttggccggc gtgcagcagg gcgtggccct cgtcggtgag ccgggcgccg gtggagcccc  11040  
               
               
                   
               
               
                 gggagaccag gacggtacgc agccggcgtt ccagccgggt gaggcggcgg ctggcggacg  11100  
               
               
                   
               
               
                 actgggtgac ccagccctgg cgttgtgcgg cgtgcagact tccgtggtcg gctacggctt  11160  
               
               
                   
               
               
                 gcaacagtgc tacatccgaa cgtctcagat cgaacattcg ctgctcctgt gcgctgtggt  11220  
               
               
                   
               
               
                 gccggcttcg ggcggtgggc gaggaggggg gaagcgctcg cacagttgtc gggtccgtaa  11280  
               
               
                   
               
               
                 ccttcccgtc acgtcagccg gtcaaccgtg cccgcggtgg gggggttggt gccggtggtg  11340  
               
               
                   
               
               
                 tgcccgttcg agcgggcggc gcgggggaag gcggaaccgg cgcagatccc gagcgcgccg  11400  
               
               
                   
               
               
                 agcaccgcgg tgccggcgaa gacgagcgtg taggcggcgg ggctcggatg gtcgccggtg  11460  
               
               
                   
               
               
                 gtgccggcgg cgagcaccat ggagccggcc tggacgccga aggagccgcc gaggctgcgc  11520  
               
               
                   
               
               
                 agcaggctgt tggtgccgac caccaccccg gtggtgccgc ccggcgaggc cagggtgatc  11580  
               
               
                   
               
               
                 agctcggtca tcgcgccgcc gaggacaccg gtggccgcgc cgttgagcag cgtgcccagg  11640  
               
               
                   
               
               
                 gcgagggagg ccatgctgac cggcaggaag gcgaagacca cggcggaggc ggcgaagagc  11700  
               
               
                   
               
               
                 acggtgccgg tgaccatcac ggcccggggc ggcagcacgc ggcccagccg tccggacagc  11760  
               
               
                   
               
               
                 agcccgccgc ccagcgtgcc gatctccatc ggcatcatca ccacgatcac accgagcccg  11820  
               
               
                   
               
               
                 gccaccccga ggccgccggc cgagcgcgga gcctcggcga tggccggcgg gaacgtcccg  11880  
               
               
                   
               
               
                 gtcacgaaca tcaccaggcc ggtgaggagg ctgaccgcgt tgagtgtcca gatcggccgg  11940  
               
               
                   
               
               
                 cggctcatca gccgcaggtc catcatcggc gtggtggtgc gccgttccca ggcgagcagc  12000  
               
               
                   
               
               
                 gcggccccgc tcaccacggc gccggccagc agcgtactgc cggtgaccga gccgatcccg  12060  
               
               
                   
               
               
                 tcgcgcccgt atctgcccag cgccagcagc accagggcgc tgctgacggc gagcagggtg  12120  
               
               
                   
               
               
                 agcccggggg cgtcgaggcg ctggccggcc cggcgcgggg tctccgggag caccgccgcg  12180  
               
               
                   
               
               
                 ccgatgagca gcagcagcgc ggccagcgcc gcgccggtgg cgaacaccca gcggtagccg  12240  
               
               
                   
               
               
                 tccgggtcgc cctccaccac cccggccagc atgatgccgg cgccgccgcc gaccccgaac  12300  
               
               
                   
               
               
                 gacgcggaga gcaccccgaa cgggccggcc agcgcacccg ccgggaaccc ctcccgcacc  12360  
               
               
                   
               
               
                 aggccgaccg cgagcgggaa gaggccgccg gccacgccca tcaccagccg agcggccagc  12420  
               
               
                   
               
               
                 agcagcccga aggtgtcggc gctcgcggcc accgcgccgc cggccgcgaa gacggcgagc  12480  
               
               
                   
               
               
                 accgccagca gtacccggcg cctgccgtac aggtcgccca ggcgccccac caccggggtg  12540  
               
               
                   
               
               
                 gccacgcacg ccaccagcag gtggccggag accacccagc cggtgtccgc cgcgccgacg  12600  
               
               
                   
               
               
                 ccgaagccgt gccgcaactg ggtgagcagc atcgtcacgg ccagttgcat gagcgcgaac  12660  
               
               
                   
               
               
                 agcccgcagg cgctggccag tacggccagc gccacggtgc tcgcgccgcg cgccggggag  12720  
               
               
                   
               
               
                 ccgtgcgccg gtgcgctcac cgctgctcgg tcaggacggg ctcggccggc gaggtgacct  12780  
               
               
                   
               
               
                 cggcggcttc gaaccggtgc cggtagtggc cgatgcggga gaccgggtag ctggggccga  12840  
               
               
                   
               
               
                 tggcggcgcg ggcgaacgcc ttgaggtcgc cgggtaccgg ggtgtagcgg ccgttggcgc  12900  
               
               
                   
               
               
                 cgaagcgctg gtcggccagg cgcatccgga ccgggcgcct gcgcagctcg ccggtggtga  12960  
               
               
                   
               
               
                 agtagccggg ccagtcggcg gtgtactcgg tggtgcggcc ggccgccggg tcgtagtcgg  13020  
               
               
                   
               
               
                 ggcgcagcat cacgtcctgc tggaaccgga agacctcggc gaggtcgggg tcgctggtgt  13080  
               
               
                   
               
               
                 cgtccacgcc gagggcggcc acgaagtcac gcagttcggt gtaggtgcgt tcgaagtcgt  13140  
               
               
                   
               
               
                 tggcgatccg cagccagccc cagttgtcga tggtccagcc gcgccgcttg ccgtaccggg  13200  
               
               
                   
               
               
                 cgaggtcggc ggccatgtcg ggctggctgg cgaccaggtt ggccagcggc agttcgggga  13260  
               
               
                   
               
               
                 tgtcgatgta gtcgtggtac agcttgcgca tccgcaggta gatcgagccg agcacggtgt  13320  
               
               
                   
               
               
                 cggggcgggc gccgaagtac tgctggagcc gttcgtagaa ggcggtgtag ccgatgtcgt  13380  
               
               
                   
               
               
                 ggcgttgccg caggtacatc gacagatagc gggtgtagca gccgttgtgc aggaactgca  13440  
               
               
                   
               
               
                 cggcctggac gaagccgaag cagtcgaccc attcgtcccg ggacatggcg ttggtctcca  13500  
               
               
                   
               
               
                 tcaccatgtc cacggtctcc gcctcgtcgt ccggggtgcc gggctcttcg acgtagagcc  13560  
               
               
                   
               
               
                 gcttgggtac ggttcgcagg ccgtaaccgg cgatcttctc gggggtgttg atgggggcgt  13620  
               
               
                   
               
               
                 tgggcaggat gccgaactcg tagacgcgga tgtcctcgtg gttgccggct tccagcaggg  13680  
               
               
                   
               
               
                 agccgatgcc gtcccggaag ctgcgcggtg actccagcgg gaggccgagg atgagttcgg  13740  
               
               
                   
               
               
                 tgtaggtgtg gatgttctcg gtggcgtacc gctgctggag tttgcggtag ttctccaggc  13800  
               
               
                   
               
               
                 cgatgttctt gcggtcgatg gcctccagca cgtcgaggtc ggtggactgc atggacaagg  13860  
               
               
                   
               
               
                 tggtgcccat cagcaggtcg gcgtcgtgcc aggtcttgct gatctcgaag acccggtcgt  13920  
               
               
                   
               
               
                 tggagttctt ggcgaagttg acccggatca gtttgggtgc cccggtggcc gcccgggcgt  13980  
               
               
                   
               
               
                 cggcgagggc gcgcgcgatc tccaggtcac gggggaggat gccgaagttg gcgtcgcaga  14040  
               
               
                   
               
               
                 cgaagaggtc ctcgacgtcg tgttcggcga accactcgat ctcctcctgg aggcgttcgg  14100  
               
               
                   
               
               
                 cgtcgaagag ccgcagcgcg ctcatggtgg ccgagcccca gtcgcagaag gcacacgagt  14160  
               
               
                   
               
               
                 aggggcagcc gcggttggtc tcccacagcg cgtagaaccg caggtcgcgt tggcggcagg  14220  
               
               
                   
               
               
                 tggccaccgc gccgtccatc acgcccagca ggtaggggct gggggtctcg atgcggcgcg  14280  
               
               
                   
               
               
                 gcagccgctc ggccgggcgg ccgggcaccg cctcggtgcc gtggcgtacc gagacgcccg  14340  
               
               
                   
               
               
                 gcaccctggt gtagtcgggg tggtcggcca gccgctcgat gagcagttcc cggaaggccg  14400  
               
               
                   
               
               
                 tctcgccctc gccgtgcacg agcacgtcga cgtaggggtg gcgggcgaag aagtcaccgg  14460  
               
               
                   
               
               
                 gccggtcggg gacgtgcggg ccgccggcga ccaccagcat ccccgggtgg cgttccttga  14520  
               
               
                   
               
               
                 ccagccgggc caccttcatc tggcggcgga agttccacac gtagcaggag agcgccagca  14580  
               
               
                   
               
               
                 cgtccgggtc ggtgatcccg gcggccatct cctggacccc gtcgaccagg aacaccggtt  14640  
               
               
                   
               
               
                 cctggaagtc gtatccggcc gcgacgcgcg gatcctgttc cgcgtaggtg cgcagcagac  14700  
               
               
                   
               
               
                 cggccaccag gggcaggaac ggcaccgcgt tgaggccgat gaagtacacc ttgcgaccgc  14760  
               
               
                   
               
               
                 tgcgcgcggc ggggacggtc atgctctcac ggctcctcgg gttcggggct gttgccggct  14820  
               
               
                   
               
               
                 gcgggcaccg ggcggtgtca tccggtgccg gcgaccgtct cgggctcgcg cgtcggcgac  14880  
               
               
                   
               
               
                 cagctctcgc gcgggtgcga ccagtcggcg ccgcgtcgca gttcccgcag catctggtcg  14940  
               
               
                   
               
               
                 aaggcgtcgt cgtcggagta gtagaagacc gacgggtcgc tctccccggt caccccgggc  15000  
               
               
                   
               
               
                 gcggtacggg cgctggcgcc ggccagcagg tcggccagtt cgccgtagaa ccgctccagc  15060  
               
               
                   
               
               
                 ggcagccggg tgcggaacag cgagtggtag cagtcgaaga gttcggggtt gtcgctgatc  15120  
               
               
                   
               
               
                 agcccgagct tggcctcgtc gtacaggtcg gtgcccggca gcggggtgag caccgagaag  15180  
               
               
                   
               
               
                 ctgggcatgt ccacctggag ttcgtcgacc gtgcggccga gccgggcgaa gtccgcctcg  15240  
               
               
                   
               
               
                 gaccagtcgg gttgcacgat gaagttggcg cggaccttga ccccgttgcc gtggaagagg  15300  
               
               
                   
               
               
                 tccagcgcgc gcctggtctg gccggggtcg gtgcccttgc ggtagccggt cagttcctcg  15360  
               
               
                   
               
               
                 tcggtcatcg actcggcacc caccagcacc gagtccagcc cgatctcggc ccagcgggcg  15420  
               
               
                   
               
               
                 atcacgtcgg ggcggcgcag cgcggtgtcg gtgcgtacgt acatgtggaa cttcttgcgg  15480  
               
               
                   
               
               
                 aagcccgcct tgtcgatggc gtcggccagt tccagcatgc ggaccggctg gatgaacgcc  15540  
               
               
                   
               
               
                 tcgtcgtcga cgacgtagag gttgtcgccg tcgatgtcgg cgatctcggc gagcacccgg  15600  
               
               
                   
               
               
                 tcgatgtcct tgaccaggta gcggcggtcg gtcatccgcc acagcgagca gaacttgcag  15660  
               
               
                   
               
               
                 gtgtacgggc agccggcggt gaagcggatg agcgccaccg gccggtagat ggagtggaag  15720  
               
               
                   
               
               
                 tagcgtccgc ggtggtgggc caggcgggtg cggtccggca tcggcaggtc gtcgagggcg  15780  
               
               
                   
               
               
                 gacggcttgg ggcgccggtc gcgttcgagc ccggtgcggg cgtcgtaggg ggcgaggccg  15840  
               
               
                   
               
               
                 cgtaccgggg cgggggtgcg gccggcctcc agttcggcgg cgaggtgggc cagtggtccg  15900  
               
               
                   
               
               
                 ccgccctcgc cggccacgat ccagtcggcg gcgaacccgg tcagccactc ggcgctgacg  15960  
               
               
                   
               
               
                 gtcgggtggt ggccgcccag cacgatcggg gtgcccggcc acagccgccg ggcctggtgg  16020  
               
               
                   
               
               
                 gtcacgtccc gggagacccg gacgctggtg gtgtagggga tggcgacgcc gatcaggtcg  16080  
               
               
                   
               
               
                 ggcgcctcgt gggtggcggc gtactcctcc agggaggtgt ccacccgcag gtcgtggatg  16140  
               
               
                   
               
               
                 gtgacgtcgt gggcgccgcg cagggcgccc gccaggtatt ccagcggcag cggctcacaa  16200  
               
               
                   
               
               
                 cagctgagcc ggtcgctgag gagggcccgc tcgttacgag gccacaccag caagaccctc  16260  
               
               
                   
               
               
                 atcggatccc tccaactcgt cggtaccggc agcggtgtcg cggaagacct cggtggccat  16320  
               
               
                   
               
               
                 ctcgtacagc cgccttgcct gggtgtgccg gtcgtcgctg cccagggcgg cggcgaacat  16380  
               
               
                   
               
               
                 gcggctcatg gcggtgccct cgtggatgcc gcgcttgggg cgccaggcga cctcgtccgg  16440  
               
               
                   
               
               
                 caggatgccg gtgaccgcgc tgcgcagcac ccacttcgcg gtgtcggggc gcaccttgag  16500  
               
               
                   
               
               
                 ccggccgcgg atgccgagcg cggtggacat cacctcgcgg gtccagtacg ggtagcgcac  16560  
               
               
                   
               
               
                 caccacgtcg cgggcgtcgg cgtaggcggg gttgaactcg ttgctgacgg cggtggcggc  16620  
               
               
                   
               
               
                 ggtctgggcg gcgaccgagc gttcgatccg ggtctcggtg ccggtgccgc cgaggccggc  16680  
               
               
                   
               
               
                 gaagatcagg tcggcgccgt aaccggagag catcacctgg cgggcgccgg tggcgatgtg  16740  
               
               
                   
               
               
                 gcccagcagg aagcaggcgg gggcggcgat ctggagggtg agcaggtccc aggtctccag  16800  
               
               
                   
               
               
                 cgagcggatc atctccggca gcagcgcggt cagttgctcc ggttcgaaga ccagctcgtg  16860  
               
               
                   
               
               
                 gtgtttgctg ccgagccgtt cggcgaacca ggcggcctgc gcgaactcgt cgccgaacgg  16920  
               
               
                   
               
               
                 ggtgcccacg gtgtacgtgg acagcgaggt cacctcgcgg gcggcgagcg cggccaccga  16980  
               
               
                   
               
               
                 ggaggagtcc acgccgccgc tgagcatcac cccggcctcg gtcagcccgg tggcgaggcg  17040  
               
               
                   
               
               
                 gccgaccgcg tgggtcagcg cgtcgcggac ggcggtgacg gcgcgttcgg ggtcggtctc  17100  
               
               
                   
               
               
                 ggtgggccgg gcgggcagcc ggtggtagcg gcgggtgagc aggggctcgg tgtcgaaccc  17160  
               
               
                   
               
               
                 ggccaccgcg agggtgaccg cggtgcccgc ggggacggcg gtgaccccgg cgaaccggcc  17220  
               
               
                   
               
               
                 gccgggcagc accgcgcggt cgccctcgcc cagcaccgga gcggtgccca gcagcggcag  17280  
               
               
                   
               
               
                 cagggcgccg gccgaggtgg cgaccagcag ggtgtcgtcg gcgccgcggg cgtagtgcag  17340  
               
               
                   
               
               
                 cgggcaggtg gcgccgttgt cgctccacag caccgcgcgg tcgtcgcgta ccagcaccgc  17400  
               
               
                   
               
               
                 gcagaagcgg gagtaggcgc ggaccgtcca ggcgatcagt tcgtccagcg gggcgtggat  17460  
               
               
                   
               
               
                 cggcgcctgg ccgcccgggg tgagcgggtc gccgtggacc acgaggacgt cggcgccgtc  17520  
               
               
                   
               
               
                 ccgggtcacc tcggtggcga gcccggtgcc ggcgccgagg tgttgcggga cggcaccctc  17580  
               
               
                   
               
               
                 cgggcggcag cgcagcagga atccggccat gtcagtagac cccctcgatc cggcgtccct  17640  
               
               
                   
               
               
                 cggtgaattc ggggctgtac gggtcgccca gccagggcca cgggtagcgt tccgcggccg  17700  
               
               
                   
               
               
                 ctccgtaggg ctggacgcgg cgggcccggt cgcgttcgag gaagccgggc agcagggcgt  17760  
               
               
                   
               
               
                 cgtcggtgag ccgccagacg cggacccggc cctcctcgcc gaacggcacc tcgttgccgt  17820  
               
               
                   
               
               
                 cgtcgtcgac cgcgtccagg gcgatgtgcg gctggcaggg cacgtagacc acgtggtggt  17880  
               
               
                   
               
               
                 cgtcctccgg ctcgaacggc ttctgccagc tgatgccggt ggtggaggtg ccgtacatgc  17940  
               
               
                   
               
               
                 cgaccacggg gaccccgggg aagaagtcct cgcgcagttg gcggtgggat tccggctcca  18000  
               
               
                   
               
               
                 tggtggtgcc ggcgtggacg atggcgcgaa gccccggcag cgcttcggtg ccgaggcgtt  18060  
               
               
                   
               
               
                 ccggcagcat ctccagcagc cgtgaggtgc agaagagcac cccgatccgc tgggcgcggg  18120  
               
               
                   
               
               
                 cgacttcggc gacctggtcc cagatgtgct ggacgtagcg gtcataggcg gccgtcatgc  18180  
               
               
                   
               
               
                 cttcctcgcc gaagatcttc acgatccgcg ggtcgaggtc gacggagaag cacatcccgc  18240  
               
               
                   
               
               
                 cccggcgttc cgcgaaggcg accaccagcc gtccggtggt gtgcggtccc atcgggccga  18300  
               
               
                   
               
               
                 cgaagagcca gtcgacgccg cgcggcacgc cgtgcaggtc gaggaactcg tcggagaact  18360  
               
               
                   
               
               
                 ccaggatgtc ggcccagtaa cgggcgcccc aggtgccgtg tttggcgggt ccggtggtgc  18420  
               
               
                   
               
               
                 cgccggtctg cgcggcccac agcggtccgc cctcggtgag gacgcggcgc ggcacgaagt  18480  
               
               
                   
               
               
                 tcgccagtgg cgtgcgccgg gacgcctcct cgaagtgtgc ctggtccggc ccgtcgcgca  18540  
               
               
                   
               
               
                 agccgatcag ttgctgggcg tccagcatgc cgtgcacctt gcgcagtgcg tcggtgccgt  18600  
               
               
                   
               
               
                 cgcgccggtc gcgctccagc cagtacgggg tgccgtcctg cgggtcgaag tggagtcgta  18660  
               
               
                   
               
               
                 cggcccgtcg cacgtcctcg tcggtgatcg gacggagctt ggacggactt ggcatcagca  18720  
               
               
                   
               
               
                 gtctccctcg tacgtcgctg tcctggcttc cgctcacccg gccgcgcccg ggatgaccgc  18780  
               
               
                   
               
               
                 cttcttccgg aacaggaagt cggcgaggta gccctcgtgc gggtcacacg ggtggtagcc  18840  
               
               
                   
               
               
                 gcggtcgtac tcctcggcgc cgaagacctt gtccaccccg ggctcctcgg ccagcgcgcc  18900  
               
               
                   
               
               
                 gagcagtccg gccgcgtcgc cgaggaccga gacgatcagc gaaccggcgc aggcggccac  18960  
               
               
                   
               
               
                 cgccttggag cgcggcacgt gggcaacggc cgtgaacggg aacggcagtt cggtgccgaa  19020  
               
               
                   
               
               
                 gagcggtgac cccgggtcga caaggagcac ggtggggcgc aggaaggcgg cgccgtccac  19080  
               
               
                   
               
               
                 ctcgacccgc agcggcaccc cggtgacggc ctcggtgacg tcgacggcac cggccgcgat  19140  
               
               
                   
               
               
                 ctcccgttcg atgcgggtgg cgagggcgtc gcgccgcgcc cggtccggga acgccggtac  19200  
               
               
                   
               
               
                 ggtggccgcc gggtcgtcca gcggcagcac cggccgggtg gcgaactcct cggcgaggcg  19260  
               
               
                   
               
               
                 gtcggcggcc tggcgggcgt ccccgagggc gatcaccgag ctgacgttgg tgcacagccg  19320  
               
               
                   
               
               
                 tccgcagccg gcgaaggcgg cccgggccag ccggggccac gcgtcgtcgg cggcgccggc  19380  
               
               
                   
               
               
                 gcccaccacc gcccggctgc ggccgaagtg gtaggtcttc gccttgcccg gcggcaggtc  19440  
               
               
                   
               
               
                 ggcggggacg tcctcgccgg gccagagcac ctggtcggcg aggcggcgca gcgccggggc  19500  
               
               
                   
               
               
                 gtcgccgtgc accaccgaga cggcgtgctc gggcagcccg gcctcgtaca gcgcctcggt  19560  
               
               
                   
               
               
                 gagcagcacc ggggtgaacg ggtcgtgccg ggaggtggac agcagcaccg ggcggcgggc  19620  
               
               
                   
               
               
                 ggcgagcgcc tggagccatt cgatgttgat ggtggggaag ttgtcggcga ccttgaccag  19680  
               
               
                   
               
               
                 caccgagcgg ccggccgggc gccagctcca gcgggggtgg tggccgccgg tgcggtaggc  19740  
               
               
                   
               
               
                 cgcgacggtg ccgtccggtg actgggcggc gaggatctcg tccatccggg ccaggtcggc  19800  
               
               
                   
               
               
                 ggcgacggtc tcgatgccgc gggcggcgcg ccggggaggc agcccgctcg ccgcggagag  19860  
               
               
                   
               
               
                 ggcggtcagc cacggctgcg cggtgccgtc ggcgacgcgt gcggtgagcg tgtccgcggc  19920  
               
               
                   
               
               
                 gcggcgcagc agcgcgaacc aggcgtcgtc gtcggtggcg cgcagccgcc gggcgaccgc  19980  
               
               
                   
               
               
                 ggcggcctcc tgggccatct ggaactggac gagccggccg gccgccccga cccgggccac  20040  
               
               
                   
               
               
                 cgtctcgccg gtggtgccgg tgagcgcggc cggcctgctg gacatcaccg gccggcgccc  20100  
               
               
                   
               
               
                 ggcgtaggcc gggacgtcga ggacggcgcc ggcccgctgc gggccggcgt gtccggtggt  20160  
               
               
                   
               
               
                 gacggtcgtc actggacctc cggtaccagt gcggccggtt cgttcgacag gttgctcgcg  20220  
               
               
                   
               
               
                 ccgtcgccgt cgagcaggcc gaggcgggtc tgcacggtct ggaggttggc gaggaacgcg  20280  
               
               
                   
               
               
                 atccgcttgt actggccctg gctgcggctg ggggtcatgt cgtcgtagag cttccacagc  20340  
               
               
                   
               
               
                 tcgtcgatgg aggcccccat gctggaggtg accgggatgt ggccggtgta gcagtcggtg  20400  
               
               
                   
               
               
                 tcgctggtct cgacggtgaa gtcgacccgc ttggccatgt ccttctccac ctcctggtgg  20460  
               
               
                   
               
               
                 aaggggacga agaagcaggg cgagacgagg tcgtgcttgt tcttgccgag ccgggcctgg  20520  
               
               
                   
               
               
                 agccaggtga tggtggtgcg catcgcctcg tcggtctcgc cggggatgcc caggatcatg  20580  
               
               
                   
               
               
                 gtggcctgca cgccgatgcc gttgttggtc aggcagctga tggcgcgttc ggtgacgtcc  20640  
               
               
                   
               
               
                 accttgaccg ggcggccgag ccgcttgagc aggttccagc tcagtgtctc cacgcccacc  20700  
               
               
                   
               
               
                 agcagccgga agcagccgga ttcgcgcagc atgcgggcca tgtcgtcgtt gatcaggtcc  20760  
               
               
                   
               
               
                 gggcgggcct tggcctccca ctcgaacttg ccctggagtc cggacttggc gatgccgtcg  20820  
               
               
                   
               
               
                 cacagctcct gcatgcgcgg gacgtcctcg acgaagtcgt cgtcctcgat gcgtatccgg  20880  
               
               
                   
               
               
                 tcgaagccgt acacctcgac cagttcgcgg atctcgtcga ccacccgggc cgcgctgtgc  20940  
               
               
                   
               
               
                 cggcgctggc cgacgcccca ctggtgcttg gagtagcagt acgcgcaggc gtaggagcag  21000  
               
               
                   
               
               
                 ccgcggctgg tgaccaggtt gccggagcgg ccccgggaga tccgccggta caggtcgagg  21060  
               
               
                   
               
               
                 tcggccaggt cgcgggcggg cttggggagt ttgtcgaggt tgaccacctg cggggcggcg  21120  
               
               
                   
               
               
                 ggggtctcca ccacttcgcc ctcgtcgtcg cggaaggtga tgccgcggac cttggcgaag  21180  
               
               
                   
               
               
                 ttcttccggc cgttcttgcc gaattcgtgg acgagttggg agaaggagta ctcgccctcg  21240  
               
               
                   
               
               
                 ccgcgcacca ccacgtcggc ggcgttctcc tcgatgagct tgcgggcgat ggggctggcg  21300  
               
               
                   
               
               
                 ccgacgccgc cgagcacggt gagcgcgttg gggtggcggt ggcgtacctc ggaggcgagc  21360  
               
               
                   
               
               
                 ttgatgccgt tcttcaggct ggaggtgagc acctggatgc cgacgatgtc cggccggtag  21420  
               
               
                   
               
               
                 ccgcgcagga actcgctggg ggtggacagc gggcgctgga ggacgaagag ctggtcgtcg  21480  
               
               
                   
               
               
                 atgaagtgca cgtcggtgcc ggcggtgtcg tggaaggtcc cttcccggag caccgaggcg  21540  
               
               
                   
               
               
                 agcgacagca ggcccagttg cggagcggag atcgactctc ccgagtacgg tgaccggcgg  21600  
               
               
                   
               
               
                 gcgttcacga ggagaacttg catgtcaggt ctgcctcctg cggttggaga gccccgggcg  21660  
               
               
                   
               
               
                 tggcggggcc gaccgccggc agccccgcgc acacggggat tccgtggcgt gaagaagcgc  21720  
               
               
                   
               
               
                 tcctgcccgg tcggcggctt ggcgccgggg cagcaggacg ggttcgaagc cggcggcggt  21780  
               
               
                   
               
               
                 tcccgggact tgcgccgtcg gtcagcggca gttgggaaga agtcttcacc agatgaacat  21840  
               
               
                   
               
               
                 gggccgtaat gcccggtcca atgcctttac cgggtcgcgc caatgccgtg aggacatggg  21900  
               
               
                   
               
               
                 atcggtctgg aacgggcggc catgcccgcg ggccatcacc gcgatgcgcc ggggacactc  21960  
               
               
                   
               
               
                 cctgcggccg ggttggtgtg gcagcatcgc tgaggccaga tcacgtgcgc tcgtcggatg  22020  
               
               
                   
               
               
                 gtgatgggaa ggtgcggatg accgcctcac atgacacggc agacgccacg gaccggaccg  22080  
               
               
                   
               
               
                 tcggttccac gtccggcgaa cgagcggcgt tcgcccgtga cggagtggtg cgttggggcc  22140  
               
               
                   
               
               
                 gcctgctgac gcctgatcag atcgacgcgc tgcggtcctc ggtggagcgt gccttcttcc  22200  
               
               
                   
               
               
                 gcgacggcca ccccgccgac ggggtacgcg atctgtccga acgccagggc cgcccgctcg  22260  
               
               
                   
               
               
                 acctggccct gctgcacaag atcaacctgt ggcggaccga cgaggcgtgc gcggcccagg  22320  
               
               
                   
               
               
                 tggccagggc cgacctggcg gaccgggccg aggcgctgct cggcgggccg gtacggctct  22380  
               
               
                   
               
               
                 accgcgacca cgtcttctac aagccgccgg gcaagggcga ccgcagccgc atggtgctcc  22440  
               
               
                   
               
               
                 accaggacaa ccgctactgg cacctggacc cgccggaggc catcacggtg tggatggcgc  22500  
               
               
                   
               
               
                 tggacgacgc caccgtggag aacgggtgcg tccactacgt cctcggcagc caccgccacg  22560  
               
               
                   
               
               
                 gccgggtgga gcacgtgcgt cccgaggagg gcgcggtgat gatcgaggcc cgtaccgagc  22620  
               
               
                   
               
               
                 aggagccggt ggcctacccg gcccccgccg gggacgccct ggtgcacagc gtcaacacgc  22680  
               
               
                   
               
               
                 tgcacggctc ggggcccaac ctcagcgacg gaccgcgccg cgcctacgtg gtggtctacg  22740  
               
               
                   
               
               
                 tgcgcgacgg ggtgacgatg cgcggcgagc cgatgacctc gttcccgctc gtcggcgacc  22800  
               
               
                   
               
               
                 tggtccgcgg cgggtgaggg cgcgccccgt caccgcgaca ccgagccgcc cgcaccggac  22860  
               
               
                   
               
               
                 cgccctccgg tgcgggcttt cgccttggcg cgtacggaaa ttgatggccc gtcagcgacc  22920  
               
               
                   
               
               
                 gaaaccgccg ccgtaccggc gcagcgcgtc cggcagctcc tcgatccggg aggtgtccca  22980  
               
               
                   
               
               
                 cggccgcccc cagccggcca gccgcatcag ccagtcgacg atgctcccgg tgaaccccca  23040  
               
               
                   
               
               
                 cacgaacagc tcccgcacca ggaacccggg gctgatgtaa ccgtcctggt agcgcacccg  23100  
               
               
                   
               
               
                 gaaccggttg gcggggtcgg cgaactcggc gagcggcacc cggtgcaccg agaccacctc  23160  
               
               
                   
               
               
                 gccgcggtca ccgcgcggtt cggcctcggc gccccaccag ccgagcaccg gggtgacccg  23220  
               
               
                   
               
               
                 gaagtcggtc caggcgatgc gcagcgggcg cagggtgccg gccaccgcga cgcctgccgg  23280  
               
               
                   
               
               
                 gtcgagcccg gtctcctcgg cggattcgcg cagcgcggtg tggaccacgt cgcggtcgcc  23340  
               
               
                   
               
               
                 cgcactcacc gatccgcccg ggaagcacac ctcgtcgggg tgggagcgca gggtgcggga  23400  
               
               
                   
               
               
                 gcgtcgtacg aggagcaggt cggtcccggc gtcgccggtg ccgaagagca ccagcacggc  23460  
               
               
                   
               
               
                 ggaggggcgg ccccgggcgg ggtcgtcgag gaggtagcgc accagctcgg gagggctgtc  23520  
               
               
                   
               
               
                 gtcggccgct tgccgggcca ggccggtcag ccaggtcgga acatcagttc ggtgtcgtgg  23580  
               
               
                   
               
               
                 gtacacgcga tcgaggtcca ccgggtcagc gtaggcaccg gggccgtccg ccatcaccct  23640  
               
               
                   
               
               
                 gatcgccgaa aaagacactc ccccgtggac tcccggtgcg cggggtcccc ggggccctgc  23700  
               
               
                   
               
               
                 catgatgggc ggcgcagcca ccgagagtga ggtcgcgtca gccatgggta gtcaccgtct  23760  
               
               
                   
               
               
                 cctccgcgcc cgcgccggga ccgccggggc cggccccagc agacgcgggc tgatcggcac  23820  
               
               
                   
               
               
                 ctcgctggcg gggatctccg ggctcgccgc cgggttcggc tccctcgggg cgcgtccggc  23880  
               
               
                   
               
               
                 cgccgccgcc cggcccggtc cggtcggcgg cacgacccgg ctgcggtggt tcggcaccaa  23940  
               
               
                   
               
               
                 cgcctgggag atcggcttcg gcgggcgcac cgtgctggtc gacccgtggc tgacccgctt  24000  
               
               
                   
               
               
                 caccgcgcag cggccggacg gacgggtgga cccggacacc ccgctcaccg tcgaccattc  24060  
               
               
                   
               
               
                 cgccgtcgac cgccacctgc gcgccgccga tctgatcctg ctcacccacg gccactacga  24120  
               
               
                   
               
               
                 ccacatcggc gatctgccgt acgtgatgcg gaagttcccg tccgccccgg tggtggccac  24180  
               
               
                   
               
               
                 cgagacccac gcccatctgc tcaccgccat gggcgccccc accgaccggg tcatctgggc  24240  
               
               
                   
               
               
                 ccgtggcggc gaatacctgg acttcggcga cttcgcggta cgcgtcctgc ccagcctgca  24300  
               
               
                   
               
               
                 cagcatgggc cccgaccacc gctacttcgc ccccggcacg ctcaccgcgc cgccgcgccg  24360  
               
               
                   
               
               
                 cgcccgtacc gtcggcgacc tgctggaggg cggcacgctc gcgtaccaca tcacctcgga  24420  
               
               
                   
               
               
                 cagcggggcg agcgtcgtca acatcggcac cgccaacgtc atcgagcggg agctgaccgg  24480  
               
               
                   
               
               
                 gctgcggccc cacgtggcca tcgtcgcggt gccgccgtgc ggggccaccc accgctatct  24540  
               
               
                   
               
               
                 ggagcgggtg ctcaccgcgc tcggccatcc gccgcacgtg atccccaccc accacgacca  24600  
               
               
                   
               
               
                 gctcgacacc ccgctgttcc ggccggccag cgtggacccc gggcagatgc gttccttccg  24660  
               
               
                   
               
               
                 cgaccaggta cgcgcgctcg gcccggggtg cgcggtgacc gaaccgcagt actgcgacgc  24720  
               
               
                   
               
               
                 gttcacgctc tgatcgcgga tcccgtgcca cgggggtgtt cccgggccgc acggtgtgct  24780  
               
               
                   
               
               
                 ggagtggacc ccgaggccgg atcaagggcc cgcgggctga agggagttca ccgggtgagc  24840  
               
               
                   
               
               
                 gcgaacagcg ggggcatcgg cggcgtgccg ggtccgcaca acgggctgac cgacgtaccc  24900  
               
               
                   
               
               
                 ggggtgcggg tcggccacgc cgggcgtacc ggggacggct ggctcaccgg ggtcaccgtg  24960  
               
               
                   
               
               
                 gtgctcgctc cgcccggcgg tgcggtggcc gccgtggacg tccgcggcgg cggccccggc  25020  
               
               
                   
               
               
                 acccgggaga ccgacgccct cgatccgcgc aacctcgtgc agaccatcga cgccgtggtg  25080  
               
               
                   
               
               
                 ctcaccggcg gcagcgcctt cgggctggac gcggcgggcg gggtggcggc ctggctggag  25140  
               
               
                   
               
               
                 gaacagggcc gggggttccc ggtcggcgcc gacccgtccc aggtggttcc ggtggtgccc  25200  
               
               
                   
               
               
                 gcggcggccc tgttcgacct gggccggggc ggtacgtggc gggcgcggcc ggacgccgcg  25260  
               
               
                   
               
               
                 ctgggccggg ccgccgtcga ggccgccgcc gcccgcccgg agggtgaccc ggtggagcag  25320  
               
               
                   
               
               
                 ggcggggtgg gcgcgggcac cggcgcggtg gtcggcgggc tcaagggcgg catcggcacg  25380  
               
               
                   
               
               
                 gccagcgtgg tgctggactc cggcgccacg gtggccgcgc tcgccgccgt caacgcggcc  25440  
               
               
                   
               
               
                 ggttccgcgg tggatccggc caccggcgtg ctctacggcg cccgtaccgg actgcccggg  25500  
               
               
                   
               
               
                 gagttcgccg gatacggggt gccggacgcg atcggcgccg acacgcacgc ccgggcgcgg  25560  
               
               
                   
               
               
                 gcacggctgg ccgaggccgc cgaggagacc gcccggcgcc gggccggcgg cgccgccacc  25620  
               
               
                   
               
               
                 ctcaacacca cgctcgccgt ggtcgccacc gacgccacgc tcacccgcgc ccaggcccag  25680  
               
               
                   
               
               
                 aagctggccg gcaccgcgca cgacgggctg gcccgggcgg tgcgcccggt gcacctgctc  25740  
               
               
                   
               
               
                 tccgacggcg acaccgtctt cgcgctctcc accggccgcc ggccgctcct gcccgaccgg  25800  
               
               
                   
               
               
                 ccggacgcca cggcggcccg cgccttcggg gtccacctgg aggccggcgc gctcaacgag  25860  
               
               
                   
               
               
                 gtgctggcgg ccggcgccga cgtcctcacc cgcgccgtgg tccacgccgt cctggccgcc  25920  
               
               
                   
               
               
                 accggggtgg acacccccgg cggggtccac ccgtcctacc gggagctgta cgcgcgtccc  25980  
               
               
                   
               
               
                 tgagccgtgc ccgaagccct gccgccgtac tcgaagccgt gaccagccgc ttcgttgacc  26040  
               
               
                   
               
               
                 ggccaactgc cgctgcctac actgcacttg acgaatcctt gacacaggct tgaccggcct  26100  
               
               
                   
               
               
                 gtgccggcgg tcccgccgcg ttcgcgggtt tggggggatc cactgatgga cgcagacgac  26160  
               
               
                   
               
               
                 tgttgggcgc gggcgggcac cgtgcggatc cgcctgctcg gcccggtgga gctggcctgc  26220  
               
               
                   
               
               
                 ggcacgcggc cggtgccggt gaccgggcgg cgccagttga gggtggtggc cgcgctcgcg  26280  
               
               
                   
               
               
                 ctggaggccg gacgggtgct ctccaccgcg gggctgatcg cctcgttgtg ggcggacgag  26340  
               
               
                   
               
               
                 ccgccgcgca ccgccgcccg gcagctccag accagcgtgt ggatgatccg ccgggcgctc  26400  
               
               
                   
               
               
                 gcctcggtgg gcgcgccgca gtgcgtcgtc cgctccaccc cggccggcta cctgctcgac  26460  
               
               
                   
               
               
                 ccggcccact acgaactcga cagcgaccgg ttccggcacg cggtgctgac cgcccgggag  26520  
               
               
                   
               
               
                 ttgcagcggg acgggcggct ggcccaggcc cgggcccggg tcgacgaggg gctggcgctg  26580  
               
               
                   
               
               
                 tggcgcggcc ccgccctcgg cgcggcggcg ggcgccggac tccagccccg ggcccgccgg  26640  
               
               
                   
               
               
                 ctggaggagg aacgggtctt cgccctggag cagcgcgccg ggctcgacct cgcgctcggc  26700  
               
               
                   
               
               
                 cgccacgaga cggccatcgg cgaactcctc gacctcatcg cccagcatcc gctgcgcgag  26760  
               
               
                   
               
               
                 gcggcctacg ccgacctgat gctcgccctg taccgttccg gccgccagtc cgacgcgctc  26820  
               
               
                   
               
               
                 gccgtctacc gcagggcgca gcgggtgctc gccgacgagc tggccgtccg ccccggcccc  26880  
               
               
                   
               
               
                 cgcctcgccg gcctggagcg ggccatcctg cggcaggacg agtcgctgct ggccggcgcg  26940  
               
               
                   
               
               
                 gcggtgccct gaccggcccg tcccggcggg gggcgggggt caggggcgga cgtaggggcg  27000  
               
               
                   
               
               
                 cgtcatgacc tccatgttgt gtccgtccgg gtcggcgaag tacgcgcccc ggccgccgaa  27060  
               
               
                   
               
               
                 cagcccgttg acgcggcccg gttcggtgtg cgcggggtcg gcgtagtacg tcacgccgac  27120  
               
               
                   
               
               
                 ggtctccagc cggtcgatca cggcgtcgaa ccggtcctcg gggacgatga aggcgtagtg  27180  
               
               
                   
               
               
                 ctgcgactgg atcggctcgt cgcgcttctc gtagtagtcg agcgtcaccc cgttgccgag  27240  
               
               
                   
               
               
                 gtcgacgggg aggaacggcc cgaacggctt gccgacctcc aggccgagga tcgcggcgat  27300  
               
               
                   
               
               
                 gaactccgcc gacaggtagc ggtcggaggc gtagacggcg gtgtggtcga ggcggacggt  27360  
               
               
                   
               
               
                 cgcggtgggc gacgcggagt cgtgcggtgt catcaggtgt ctctccagtc ttcggaaact  27420  
               
               
                   
               
               
                 gcgggagcga ggcgccacgc gtgggcgccg gaaacgaaga cacggaagac gggcgggcct  27480  
               
               
                   
               
               
                 cgtccccacc ccggcgtcaa gccgaggccg ggaccctcac tcgtgcgtgg cccaaggccg  27540  
               
               
                   
               
               
                 acccggcagt cacgtccgtg atcataacgg cggtccggac gcccggacaa cgccgttacc  27600  
               
               
                   
               
               
                 gggcgcgggg cggtcagccc ccggacgcct gcggggggcg gcgcagcggg ccccagtcgc  27660  
               
               
                   
               
               
                 cacgctgccg ggcgacctcg tcgcgggcct cgtggatcac ctcggggtcg atccaggcga  27720  
               
               
                   
               
               
                 tcgggcgtac gtcggtgagc agcggttcgt tgtcggggcc gcgtcccacc tcccggccgc  27780  
               
               
                   
               
               
                 gcagcaccca ggggcggacc ccgggaccga tgtcgtggcg caggtggcag tagtcgtaca  27840  
               
               
                   
               
               
                 ggcggcgggc cacccacagc cggagcgggc ggccggccca ccagtcgtcc acgtcgagcg  27900  
               
               
                   
               
               
                 ggttcgccga caggccgggc agcgagatgc cggtgaggct gtcggcgctc ccggtctccc  27960  
               
               
                   
               
               
                 gcaggtcgta gcgggggccg cgggaccagc gcacgtacag cccgcggctg ccgtcggcga  28020  
               
               
                   
               
               
                 gccgcgcgag gtcgtcgagg ctgctgagca cgggcagccc ggccgaagag gtcacaggcg  28080  
               
               
                   
               
               
                 acctccggcg ggcgggtacg gccgaccgga catgtctgcc gcgtaccccg gaccacgccg  28140  
               
               
                   
               
               
                 gtgacacccg gcgcacccgt cccgggcggt acgcccgccg gggcggtacg ggtggccgcc  28200  
               
               
                   
               
               
                 ggaacgcggg gtaggcgcgg accatgaaca ctctcgcatg gtggttacgg ctgacggtcc  28260  
               
               
                   
               
               
                 tggcggtggc gggcggcgcg gtcgccctgc tggtacagca ctggacggac gggcgcccgt  28320  
               
               
                   
               
               
                 ggccggaggc gggcgtcccc gctgcgctgc tggtcgtggt ggcgctgctg atgggggtgg  28380  
               
               
                   
               
               
                 tctcccggcg gtcgcggcgc gatctgtggt gacaccccgg ggcggcggct acgcgccggg  28440  
               
               
                   
               
               
                 cgaacaccgg cggcgtcccg cgctccgcac ggcacagtcg gatcatgacg aaccgaacag  28500  
               
               
                   
               
               
                 ccgtactctc cgacatccac ggggtgcttc ccgcactgga agccgtgctc gccgagcccg  28560  
               
               
                   
               
               
                 aggtgcgggc cgccgaccgc gtcgtcctca ccggtgacat cgcctgcggc ccgcaaccgg  28620  
               
               
                   
               
               
                 ccgaggtgct cgacctgttg accgcgctgg gcgaccgggt gacctgggtc gccggcaacg  28680  
               
               
                   
               
               
                 ccgaccgcga actggtggag ttccggcgcg gggtacgcga gacgatcccc gaccccatcg  28740  
               
               
                   
               
               
                 gcccgtgggc cgcgcggcag ctccgccccg accacctgga gctgctggcc tccctgccgc  28800  
               
               
                   
               
               
                 tttcggtgcg gctgccggtg gccgggctgg gcacggtgct cttctgccac gccacaccac  28860  
               
               
                   
               
               
                 gggacgacga ggaggtggtg gtggtcgact cgcgtccgga ccgctggcgt gaggtcttcg  28920  
               
               
                   
               
               
                 acggcctcgg ccccgacgtg gacgccgtga tctgcggcca cacccacatg cccttcgtcc  28980  
               
               
                   
               
               
                 gcctcgccca cggccgcctg gtggtcaacc ccggcagcgt cggcatgccc tacggccgct  29040  
               
               
                   
               
               
                 ccggcgccca ctgggccctc ctcggccccg gcgtcgacct gcgccgcacc ccctacgaca  29100  
               
               
                   
               
               
                 ccgacgccgc catcgcccgc ctcacccgcg actgcggcta ccccgccatc gccgagtggg  29160  
               
               
                   
               
               
                 ccgactacta cgtgcgcgcc cgggcgacgg acacggaggc gctggcggcg ttcggcccga  29220  
               
               
                   
               
               
                 gggacggacg cggggcggaa gggtagtcca ccgggggcgc ggggcggtcg gggtcggggc  29280  
               
               
                   
               
               
                 cgccgggtgt gcgggacgat cggcgctggg gcgcggggcg ttgtcggtgg ccggtgggat  29340  
               
               
                   
               
               
                 gctcgccgtc atgacgccct ggaccctcac cgccatcgaa cgtgccctgc gcgccagttg  29400  
               
               
                   
               
               
                 ggccgcggac acctgctccc ccgacgatct ggcccgcgcc ccgtggtccc cgggcaaccc  29460  
               
               
                   
               
               
                 ggcgtggggg cactgcgaca tcaccgcgct gctcgtcaac gatctgctcg gcggtgacct  29520  
               
               
                   
               
               
                 ggtgtgcggc gaggtacggc tcggtacatc agttccggct cgggtagagc atcgtcgcgc  29580  
               
               
                   
               
               
                 cgcgcctggt acgccgtccc ccggggccga cccggcatcg ctgggcggaa tacctgctgc  29640  
               
               
                   
               
               
                 tgcgcgagcg ggtggtcggc aggctcggcg tgctgcccga ccctgcgggg accaactcca  29700  
               
               
                   
               
               
                 cacagtgaac aactcgttca catcaacccg ttgacaatgc ccgcaaccga acacatgatt  29760  
               
               
                   
               
               
                 gactcatgcc tgagtccatc gaagatccgt tcaccccgcc cagccccgag caggcgcgcg  29820  
               
               
                   
               
               
                 ccgagcgcgt ggccacctcg ctgttccgga tagccgagcg gcacgccgcg acggaggagc  29880  
               
               
                   
               
               
                 ggcggcggcg tcagacgcat ccgtacgtgc tcgctccgca cgaggcggtg cggctggtgg  29940  
               
               
                   
               
               
                 ccttcctgct gagcggggcc gcgcagcacg aggaggacga gccggaggtg gaccgcgcgg  30000  
               
               
                   
               
               
                 atctgctggc cgcgctcacg ctgctgccgg cggcccgcgc cgacctggac gagatcgagg  30060  
               
               
                   
               
               
                 ccggcctgct caagatggcc cggggccggg gcctcacctg gccggagata gccttcggcc  30120  
               
               
                   
               
               
                 tcggcctcgg caccccgcag gccgcgcgcc agcgctacga acgcctctcc ggccgcatat  30180  
               
               
                   
               
               
                 ccgccgaccc cgagtgacca ccggccgccc ccggcgccac cgggaccgtc cagaccgcct  30240  
               
               
                   
               
               
                 ttaaggaaga tttacggtcc cgttggcacc gaaagatccg tcttcgcccg ggcgtggttg  30300  
               
               
                   
               
               
                 tggaacgacg cgctgattgg ggcgagttgg ccggttcccg gccggttatg cgcggccttg  30360  
               
               
                   
               
               
                 acgccctggt ggcgcggtgg ttccctcagt ggccgagtga cgcaacgtcg cgcttgcggc  30420  
               
               
                   
               
               
                 cccgggtgcc cacgacggca cccgcgccgc agccgctgga agccgcaacg tccgcaatcc  30480  
               
               
                   
               
               
                 gcactccacc cggtccacgc agcaagcaag gcgcagcagc accgcccacc acgggcaacg  30540  
               
               
                   
               
               
                 caccggtgac gcgcggggga cggcgcgtac ccgcgacggc acggcatgcc gcggagccct  30600  
               
               
                   
               
               
                 gcccgcacct ccccgccgac gacttcaccc acgcccgcgc gcgtcaccgc gcgggcgcac  30660  
               
               
                   
               
               
                 ccggcgctgc ccccggccca cccaggagga cgccatgttc caccgcatca gccggcccgg  30720  
               
               
                   
               
               
                 ccgaggatta cgcgacgggg ccggaacggt cacacgcggc cgaagacacc gcccggtacg  30780  
               
               
                   
               
               
                 tgggccgggc gagcggtcgc ggtgttcgcg gcccgcctcg gccctggccg tggcgctgac  30840  
               
               
                   
               
               
                 gctggcgctc accgcggggg tggtctcccc cgccatcgcc gcgacgacgc ccagagccgc  30900  
               
               
                   
               
               
                 cccgtccgcc gctcccccgc cgcccgcgcc gaccaccgcc gccggcgacg tgctggtcaa  30960  
               
               
                   
               
               
                 cggctggggc gacggcgccg gttaccacct ggacgtcgcc accggcagcg gcggctacga  31020  
               
               
                   
               
               
                 ctggcgtgag ctggccgtgc tgcgcccggc gggcatcgac gactcgtcct ggacgggcta  31080  
               
               
                   
               
               
                 ccagtgcgtc tccggcgacg ggcggtacgc ggcggtggcg atcctgcccg cgtccgcggt  31140  
               
               
                   
               
               
                 gaacctggcc gtcgcccgcg accacggtgc cttcgcctac tccgtcgacc tgcgctccgg  31200  
               
               
                   
               
               
                 cgcggtcaag ccggtggcgg cgggcgtggc gctcaagtac cacaccccgg ggtgcggcac  31260  
               
               
                   
               
               
                 cggcgacacc gccgagttca ccatcgaccc gggcaacgac cagcgggcca cccaggtgct  31320  
               
               
                   
               
               
                 ctcggccgat ctgccctccg gacgcctcac ccacgtcacc accgtgcccg gccaggtgac  31380  
               
               
                   
               
               
                 ctccgtggtc cccgccggtg acgggccggt cggggtgctc ggcggcgaac tggtgcggat  31440  
               
               
                   
               
               
                 accggaggac ggcggccgga cggcacgccc ggtcgcgctg gcgtcggtcg gcgggctcgc  31500  
               
               
                   
               
               
                 ctacgacctg cgtccggcgg ccggcggcgg cgtggacttc gcggtgcaac gggccgcggg  31560  
               
               
                   
               
               
                 ccgcagctcg ttgatcgtcc gggagcgctc cggacacctc accacgctgg gcgagggcac  31620  
               
               
                   
               
               
                 ccacaccggt ctgcggctga tgcagggcag ggcgggccac gccctggcgc tggaggccac  31680  
               
               
                   
               
               
                 ccgcctggtc ccgggcagcg gggtgcgcgc cgtcgccacc cgtggtctgc cgggtgccgc  31740  
               
               
                   
               
               
                 caccggtgtc tcgctggacg gcggcgcggt gctgggcctc ggcgccagga ccgccgcgtc  31800  
               
               
                   
               
               
                 ggcgccactg gtgctggcca cccgcaccgg caaggtgctc aagcgctccg ccgcgccctc  31860  
               
               
                   
               
               
                 ggcccggcgg ccggacaccg tgctgccggt gccgccgccc ggcgcgttcg gcggtgccgc  31920  
               
               
                   
               
               
                 gggcgggctc accccgtcgt cggcgggcgt cagggggacg gtctccccgc tgaccgcgac  31980  
               
               
                   
               
               
                 gcccaagtgc gcggtgggcc gcaacgagga gaaccggcag gtgatgcagc ccggcacggc  32040  
               
               
                   
               
               
                 ccaggtgtcg tgggcggtgc agatggccga gcaggggctg ctgaccggct cggcgtacca  32100  
               
               
                   
               
               
                 gcgccccgcc aacttcgcca acctggggct cgtcgcctac tcgcccaacg gcgacttcgg  32160  
               
               
                   
               
               
                 caaggtggcg ctccaccacc cgtccggtga cagctgggac tcggtgccgc gctcggtgta  32220  
               
               
                   
               
               
                 ccaggccatc gtggcccagg agagcaacta cagccaggcg tcctggcact cgctgccggg  32280  
               
               
                   
               
               
                 catcccgggc aacccgctga tcgccgacta ctacggcgcc ggcggatcc              32329  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 2  
               
               
                 &lt;211&gt; LENGTH: 250  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 2  
               
               
                   
               
               
                 Met Ile Pro Arg Ser Phe Pro Ala Leu Gly Asp Arg Gly Gly Gly Ala  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Arg His Arg Pro Ala Asp Arg Arg Pro Asp Arg Ala Ala Pro Pro Gly  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Gly Pro Ser Ala Gly His Pro Leu Pro Ala Phe Leu Arg Ala Arg Arg  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Leu Arg Ser Gly Leu Ser Gln Glu Gly Leu Ala Trp Arg Leu Asp Val  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Ser Thr Arg Thr Val Ser Asn Trp Glu Arg Gly Gln His Gly Val Asp  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Pro Arg Arg Val Ala Asp Leu Ala Ala Ala Leu Ala Leu Thr Arg Glu  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Glu Glu Arg Glu Leu Ala Gly Leu Ala Gly Ser Arg Thr Pro Ala Ala  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Arg Pro Ala Pro Ala Pro Glu Thr Pro His Pro Gly Asp Pro Ala Gly  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Phe Ala Arg Glu Trp His Arg Gly Phe Arg Asp Val Gly Met Pro Ala  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Tyr Leu Arg Asp Pro Ala Trp Arg Leu Leu Ala Cys Asn Ala Ala Tyr  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Thr Arg Leu Phe Ser Gly Val Ala Arg Val Pro Glu Ala Ile Pro Arg  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Glu Asn Leu Ala Arg Phe Ile Cys Leu His Pro Asp Ala Pro Arg Leu  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Leu Ala Asp Trp Tyr Glu Gly Trp Leu Val Pro Leu Leu Cys Glu Ile  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Ser Asp Asp Leu Arg Ala Ala Pro Pro Arg Ser Pro Leu Tyr Ala Leu  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Leu Lys Ala Val Leu Ala Arg Pro Glu Ile Ala Arg Ala Trp Arg Thr  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Glu Val Pro Ala Arg Ala Ala Ala Arg Ile  
               
               
                                 245                 250  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 3  
               
               
                 &lt;211&gt; LENGTH: 296  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 3  
               
               
                   
               
               
                 Met Thr Asp Ala Gln Pro Ser Gly Pro Val Val Glu His Gly Arg Gly  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Asp Leu Thr Ala Glu Glu Arg Arg Gln Lys Leu Ser Phe Leu Arg Glu  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Lys Arg Asp Ser Val Asp Arg Ser Ser Phe Glu Ala Arg Tyr Pro Val  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Glu Val Pro Arg Arg Leu Pro Gly Arg Gly Arg His Ala Pro Gly Leu  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Thr Leu Val Glu Met Gly Arg Leu Leu Gly Leu Arg Asp Gly Ser Trp  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Tyr Ala Asp Leu Glu Arg Gly Gln Val Asp Asn Ala Pro Val Asp Arg  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Leu Phe Lys Val Ala Glu Leu Leu Asp Leu Thr Pro Arg Gln Tyr Glu  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Phe Leu Cys Val Tyr Ala Cys Arg Pro Lys Pro Gly Tyr Pro Ala Ala  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Gly Leu Pro Gly Gly Tyr Arg Glu Val Leu Asp Leu Tyr Gln Gly Pro  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Ala Tyr Phe Gln Asp Ala Gly Trp Asn Leu Leu Arg Pro Lys Met Tyr  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Asn Ala Ala Ala Glu Ala Leu Phe Asn Gly Ile Pro Asp Asp Phe Asn  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Phe Ile Arg Trp Val Leu Leu Glu Arg Ser Val Arg Arg Pro Pro Glu  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Gly Gly Arg Arg His Ala Trp Leu Pro Asp Phe Trp Gln Val Trp Ala  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Pro Arg Ala Leu Pro Val Val Arg Ala Ala Tyr Val Ala Arg Pro Asp  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Asn Ala Thr Leu Ala Arg Leu His Ala Asp Leu Ala Ala Asp Pro Glu  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Ile Gly Pro Ile Tyr Gln Gly Arg Leu Pro Pro Tyr Pro His Thr Asp  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Gly Asp Leu Arg Pro Phe Val His Gly Ser Thr Gly Glu Arg Gly Met  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Val Arg Ile Asn Val Leu Thr Pro Arg Gly Ser Asp Asp Thr Leu Met  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Leu Leu Asn Trp His Pro Gly Ala  
               
               
                     290                 295  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 4  
               
               
                 &lt;211&gt; LENGTH: 259  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 4  
               
               
                   
               
               
                 Met Asp Leu Arg Met Ser Gly Lys Thr Ala Val Val Thr Gly Ala Ser  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Arg Gly Ile Gly Leu Ala Val Val Arg Thr Leu Thr Gly Glu Gly Val  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Arg Val Val Gly Ala Ala Arg Thr Val Thr Ala Glu Leu Lys Asp Ala  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Gly Ala Val Pro Val Ala Val Asp Leu Ser Thr Pro Glu Gly Cys Ala  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Glu Leu Val Gln Arg Ala Leu Ala Glu Leu Gly Gly Ile Asp Leu Leu  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Val Asn Asn Ala Gly Gly Gly Asp His Phe Thr Ala Ala Gly Phe Leu  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Thr Ala Asp Asp Glu Ile Trp Glu Arg Ser Trp Ala Leu Asn Phe Phe  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Ala Pro Val Arg Leu Ile Arg Ala Ala Leu Pro Ser Leu Ile Glu Arg  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Arg Gly Ala Ile Val Asn Val Ser Ser Ile Gly Ala Arg Asn Ala Thr  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Gly Pro Ile Asp Tyr Ala Thr Ala Lys Ala Ala Leu Asn Thr Leu Gly  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Lys Ala Leu Ala Ala Glu Phe Gly Pro Arg Gly Val Arg Val Asn Thr  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Val Ser Pro Gly Pro Thr Arg Thr Pro Val Trp Glu Asp Pro Asp Gly  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Tyr Gly Ala Gln Gln Ala Ala Leu Gly Gly Gln Glu Leu Ala Asp Tyr  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Val Ala Arg Val Pro Ala Arg Ser Gly Gln Leu Thr Gly Arg Leu Val  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Glu Pro Gly Glu Val Ala Asp Leu Ile Ala Phe Leu Gly Ser Asp Leu  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Ala Ala Ser Val His Gly Ala Asp Tyr Val Ile Asp Gly Gly Ala Leu  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Lys Thr Val  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 5  
               
               
                 &lt;211&gt; LENGTH: 360  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 5  
               
               
                   
               
               
                 Met Ala Arg Leu Thr Arg Ala Glu Thr Gln Glu Arg Asn Arg Asp Lys  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Val Leu Asp Ala Ala Arg Glu Glu Phe Ala Glu Arg Gly Tyr Arg Asp  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Ala Arg Ile Asp Ala Ile Ala Glu Arg Ala Gly Leu Thr Arg Gly Ala  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Val Tyr Ser Asn Phe Pro Gly Lys Arg Ala Leu Tyr Phe Ala Val Leu  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Ala Ala Leu Ala Glu Arg Val Pro Glu Gly Pro Pro Pro Arg Pro Val  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Arg Ser Gly Gly Asp Ala Leu Ala Ala Phe Ala Arg Ala Trp Val Ser  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Arg Leu Pro Pro Ala Gly Asp Asp Gly Pro Gly Pro Ala Arg Leu Ala  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Met Asp Leu Met Pro Glu Val Ile Thr Asp Ala Ala Thr Arg Arg Pro  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Phe Ala Gln Leu Leu Lys Leu Asp Ala Ile Leu Leu Gly Leu Ala Leu  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Glu Arg Leu Glu Pro Ala Gly Arg Pro Ala Arg Arg Met Val Arg Val  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Ala Glu Ala Val Leu Thr Ala Leu His Gly Thr Ala Gln Leu Ala Ala  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Ala Ala Pro Gly Phe Leu Asp Pro Leu Asp Ala Val Arg Val Cys Glu  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Arg Leu Ala Gly Leu Pro Leu Asp Asp Asp Pro Pro Pro Ala Pro Gly  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Leu Pro Pro Val His His Val Asp Glu Pro Trp Ser Pro Pro Pro Ala  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Thr Asp Ala Val Thr Gly Asp Pro Leu Pro Ala Asp Gly Glu Pro Asp  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Gln Val Val Thr Val Leu Gly Leu His Arg Leu Glu Ala Ala Glu Asp  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Ala Val Arg Ala Ala Pro Pro Asp Thr Pro Val Thr Ala Val Leu Val  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Thr Ala Asp Pro Gly Glu Leu Gly Ala Leu Ala Arg Leu Ser Val Ala  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Glu Leu Cys Gly Cys Leu Arg Gln Ala Phe Pro Ala Ser Ala Arg Pro  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Pro Leu Arg Val Val His Asp Pro Ser Gly Ala Phe Ala Ala Ala Ala  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Gly Val Pro Ala Val Asp Asp Arg Thr Glu Thr Ala Ile Arg Leu Ala  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Ser Ala Arg Val Thr Ala Arg Ala Gln Gly Pro Gly Ala Ala Arg Ala  
               
               
                             340                 345                 350  
               
               
                   
               
               
                 Val Ala Ala Thr Pro Arg Arg Gly  
               
               
                         355                 360  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 6  
               
               
                 &lt;211&gt; LENGTH: 212  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 6  
               
               
                   
               
               
                 Met Glu Pro Met Leu Thr Thr Ala Leu Ala Phe Leu Gly Ala Cys Val  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Leu Ile Ala Ala Ala Pro Gly Pro Ser Thr Met Leu Ile Ile Arg Gln  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Ser Leu His Ser Arg Arg Ala Gly Phe Leu Thr Val Leu Gly Asn Glu  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Thr Gly Val Leu Thr Trp Gly Val Val Ala Ala Leu Gly Leu Thr Ala  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Leu Leu Ala Ala Ser Arg Thr Ala Tyr Asp Val Met Arg Ile Gly Gly  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Ala Val Val Leu Val Trp Tyr Gly Val Gln Thr Leu Arg Ala Ala Arg  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Arg Gly Glu Ala Arg Pro Ser Ala Ala Asp Asp Glu Ala Ala Val Val  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Pro Arg Ser Gly Trp Lys Ile Tyr Arg Ser Gly Leu Leu Leu Asn Leu  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Ala Asn Pro Lys Ala Ala Val Phe Ala Met Ser Phe Leu Pro Gln Phe  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Val Pro Ala Gly Ala Pro Lys Leu Pro Val Ile Thr Ala Leu Ala Ala  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Phe Gln Ala Leu Phe Glu Val Gly Tyr Tyr Gly Met Tyr Val Trp Phe  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Val Gly Arg Met Lys Arg Val Ile Ser Arg Ala Gly Val Arg Arg Arg  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Leu Glu Gln Val Ser Gly Gly Val Leu Val Leu Leu Gly Ile Arg Met  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Ala Val Glu Ser  
               
               
                     210  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 7  
               
               
                 &lt;211&gt; LENGTH: 363  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 7  
               
               
                   
               
               
                 Val Thr Leu Pro Thr Glu Thr Trp Ala Val Arg Ile His Arg His Gly  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Gly Pro Glu Val Leu Val His Glu Arg Leu Pro Leu Pro Pro Leu Gly  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Pro Ala Asp Val Leu Val Ala Val Asp Thr Ala Ser Val Ser Gly Trp  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Asp Val Lys Tyr Arg Arg Gly Leu Pro Pro Gly Ala Arg Leu Pro Gly  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Arg Glu Arg Tyr Arg Leu Pro Leu Gln Leu Gly Arg Glu Ala Ala Gly  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Thr Val Leu Ala Thr Gly Pro Glu Ala Ala Gly Arg Phe Arg Pro Gly  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Asp Arg Val Val Ala Val Val His Pro Glu Asn Pro Arg Ala Pro Glu  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Thr Val Arg Gly Leu Gly Asn Leu Ser Thr Gly Ile Ala Leu Pro Gly  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 His Gln Ala Pro Gly Gly Tyr Ala Arg Tyr Leu Ile Cys His Gln Asp  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Met Trp Leu Pro Leu Pro Ser Gly Val Asp Leu Glu Gln Ala Ala Val  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Thr Leu Trp Pro Tyr Ala Thr Cys His Arg Val Leu Arg Asp Arg Leu  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Arg Val Ala Leu Gly Glu Thr Leu Leu Val Cys Gly Ala Thr Gly Ala  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Met Gly Leu Ala Ala Leu Arg Leu Ala Arg Leu Thr Gly Val Arg Val  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Ile Ala Met Thr Arg Tyr Arg Ala Lys Glu Arg Ala Leu Arg Thr Ala  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Gly Ala Asp Glu Val Val Val Ala Gly Asp Pro Arg Gln Ala Cys Glu  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Ala Val Arg Ala Leu Thr Gly Gly Glu Gly Val Asp His Ala Val Asp  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Phe Thr Gly Ser Ala Ala Leu Leu Arg Leu Ala Val Asp Ser Leu Arg  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Leu Gly Gly Arg Leu Cys Pro Ala Ala Thr Gln Arg Pro Pro Gly Pro  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Leu Pro Val Thr Thr Gly Asp Leu Thr Arg Leu Glu Ile Thr Val Tyr  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Gly Ile Arg Gly Ala Arg His Arg Asp Ala Leu Arg Val Leu Ala Leu  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Leu Gly Asp Gly Ser Leu Pro Ala Thr Pro Ile Ala Ala Arg Phe Pro  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Leu Ser Arg Ala Gly Ala Ala His Glu Phe Leu Glu His Asn Thr Thr  
               
               
                             340                 345                 350  
               
               
                   
               
               
                 Ala Val Gly Arg Val Val Leu Lys Pro Gly Trp  
               
               
                         355                 360  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 8  
               
               
                 &lt;211&gt; LENGTH: 294  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 8  
               
               
                   
               
               
                 Met Gly Ala Ala Ala Gly Glu Arg Arg Thr Leu Ser Arg Lys Arg Gly  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Thr Thr Val Asp Val Pro Val Lys Gln Glu Ser Arg Gln Asp Arg Phe  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Glu Asp Gln Asp Glu Asp Arg Phe Ala Ala Gln Glu Ser Ile Glu Cys  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Ser Arg Leu Gly Asp Gly Ile Ala Leu Ala Glu Phe Ser Gly Ala His  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Glu Gln Asn Pro Phe Ser Arg Ala Arg Met Arg Glu Leu Thr Ala Leu  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Met Arg Glu Leu Asp Ala Asp Glu Lys Val Arg Cys Val Val Leu Tyr  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Gly Gly Ala Gly Arg Ser Phe Gly Val Gly Gly Asp Phe His Glu Val  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Ser Glu Phe Thr Gly Gly Asp Glu Val Asn Ala Trp Ile Asp Asp Ile  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Thr Asp Leu Tyr Thr Thr Val Ala Ala Ile Ser Lys Pro Val Ile Ala  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Ala Ile Asp Gly Tyr Ala Ile Gly Val Gly Leu Gln Ile Ser Leu Cys  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Cys Asp Tyr Arg Leu Gly Ser Glu Gln Ala Arg Leu Val Met Pro Glu  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Phe Arg Val Gly Ile Ala Cys Asn Phe Gly Gly Phe Met Leu Glu Ala  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Ala Ala Gly Arg Thr Val Met Gln Arg Met Leu Leu Thr Cys Asp Glu  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Trp Pro Ala Glu Arg Ala Leu Ala Asp Gly Leu Leu His Glu Thr Val  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Ala Ser Pro Arg Leu Leu Asp Arg Ala Leu Glu Leu Ala Arg Thr Ile  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Ser Gly Tyr Thr Ala Glu Ala Val Gln Ser Thr Arg Pro Arg Val Asn  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Ala Pro Phe Val Ala Gly Leu Glu Arg Ile Arg Arg Glu Ala Lys Glu  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Ser His Arg Arg Ala Phe Ala Ala Gly Glu Ala Gln Val Arg Met Arg  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Arg Val Ile Gly Arg Ser  
               
               
                     290  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 9  
               
               
                 &lt;211&gt; LENGTH: 327  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 9  
               
               
                   
               
               
                 Val Ser Pro Arg Arg Leu Val Pro Ile Arg Pro Ala Asp His Leu Pro  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Ala Leu Val Arg Leu Ala Ala Asp Arg Asp Arg Ala Ala Leu Gly Arg  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Val Glu Val Gly Ala Thr Trp Ile Ala Gly Arg Leu Ala Ala Pro Gly  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Leu Asp Pro Glu His Asp Thr Ala Leu Leu Thr Gly Ser Asp Gly Gln  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Val Ala Gly Ala Val Trp Leu Ser Arg Ser Ser Gly Arg Ser Ala Trp  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Asp Ala Glu Leu Leu Leu Ala Pro His Ala Thr Pro Asp Asp Ala Ala  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Ser Leu Leu Asp Phe Ala His Arg Arg Cys Arg Thr Ile Ala Ala Gly  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Arg Pro Glu Gly Glu Val Cys Leu Ser Cys Phe Val Ser Glu Arg Glu  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Thr Ala Leu Arg Ile Ala Leu Ser Ala Tyr Gly Phe Ala Ala Pro Arg  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Pro Tyr Leu Arg Met Ser Val Pro Leu Gly Gly Ala Thr Ala Gly Glu  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Pro Pro Val Pro Gly Ala Val Val Arg Val Pro Glu Gly Glu Ala Gly  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Leu Arg Ala Phe His Ala Val Lys Asn Arg Ala Phe Ser Ala Glu Glu  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Ala Gly Met Glu Pro Asp Gly Phe Glu Glu Trp Leu Arg Trp Thr Gly  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Ala Asp Pro Gly Ala Asp Pro Ser Gln Arg Ala Leu Leu Glu Leu Asp  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Gly Glu Pro Val Gly Phe Ala Asn Val Thr Asp Arg Met Ala Gln Thr  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Arg Gly Ala Ala Tyr Leu Arg Gln Ile Gly Val Leu Pro Arg Met Arg  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Gly Arg Arg Leu Gly Ala Phe Leu Leu Arg Ser Val Met Ala Ala Ala  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Arg Ala Arg Gly Arg Gly Glu Met Val Leu Thr Val Asp Thr Gly Asn  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Arg Ala Gly Leu Ala Leu Tyr Arg Ala Thr Gly Trp Arg Glu Glu Ser  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Arg Phe Tyr Asp Tyr Ala Tyr Arg Val Thr Ala Thr Pro Ala Pro Ala  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Gly Glu Val Ser Ser Ala Arg  
               
               
                                 325  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 10  
               
               
                 &lt;211&gt; LENGTH: 263  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 10  
               
               
                   
               
               
                 Met Pro Val Thr Gln Ser Ile Gln Ala Leu Ser Asp Glu Leu Arg Arg  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Asp Gly Val Val Ala Leu Asp Asp Leu Val Pro Glu Ser Val Leu Glu  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Val Met Arg Arg Gly Cys Ala Glu Leu Ile Gly Arg Thr Glu Arg Met  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Arg Ile Ser Thr Glu Glu Trp Gln Leu Glu Ala Glu Gly Glu Gly Gly  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Gly Trp Ala Ala Arg Ala Ala Gly Lys Glu Cys Ile Pro Gly Lys Val  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Arg Ile Ile Gly Arg Ala His Glu His Ser Ala Asp Leu Ala Ala Val  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Pro Asp Leu Val Gly Leu Asn Glu Lys Leu Ile Glu Pro Leu His Gly  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Leu Pro Gly Asp Phe Tyr Asp Cys Phe Leu Trp Ala Lys Pro Ser Arg  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Val Gly Ser Gln Lys Pro Trp His Gln Asp Ala Ile Phe Leu Ala Asp  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Glu Trp His Glu Lys Tyr Val Asp Val Tyr Thr Ile Trp Ile Ala Val  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Asp Asp Ala Arg Glu Asp Asn Gly Cys Leu Arg Phe Leu Pro Gly Ser  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 His Arg Glu Arg Lys Leu Tyr Glu Pro Asp Gly Ile Asp Pro Gly Asp  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Ile Phe Ala Ser Pro Arg Glu Pro Ser Leu Asp Ile Ala Arg Ile Trp  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Pro Gly Leu Thr Pro Val Thr Leu Pro Arg Lys Ala Gly Ser Ala Leu  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Leu Phe Asn Gly Tyr Val Ala His Thr Ser Ala Pro Asn Thr Thr Glu  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Asp Asp Arg Arg Ala Val Ser Tyr Cys Tyr Ser Leu Pro Arg His Pro  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Ala Gly Pro Glu Ser Gly Arg  
               
               
                             260  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 11  
               
               
                 &lt;211&gt; LENGTH: 224  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 11  
               
               
                   
               
               
                 Met Val Cys Ala Ala Ser Ser Pro Ala Gly Ala Leu Leu Val Asp Trp  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Gly Gly Val Leu Thr Gln Pro Phe Tyr Ala Gly Ile Ala Glu Trp Ala  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Ala Arg Asp Gly Val Asp Ala Asp Ala Phe His Ala Leu Leu Ala Arg  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 His Leu Gly Pro Gly Ala Pro Gly Gly Ala Ala Ala Ser Val Phe His  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Arg Val Glu Arg Gly Glu Val Pro Val Ala Glu Leu Glu Val Thr Leu  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Ala Glu Ser Leu Arg Arg Pro Asp Gly Thr Gly Pro Pro Ala Glu Gly  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Leu Ile Gln Arg Met Phe Gln Pro Phe Thr Met Ala Gly Ala Met Val  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Glu Leu Val Arg Arg Val Arg Ala Ser Gly Ala Ala Val Ala Leu Leu  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Ser Asn Ser Trp Gly His Thr Tyr Asp Arg Thr Gly Trp Asp Gly Leu  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Phe Asp Glu Val Val Ile Ser Cys Glu Val Gly Met Arg Lys Pro Glu  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Pro Glu Ile Tyr Arg Tyr Thr Ala Arg Arg Leu Gly Val Ala Pro Arg  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Arg Cys Val Phe Leu Asp Asp Leu Gly Arg Asn Val Arg Ala Ala Ala  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Ala Val Gly Met Thr Ala Val Gln His Thr Ser Val Glu Glu Ser Ser  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Arg Glu Leu Ala Arg Phe Phe Asp Val Ser Pro Leu Pro Ala Gly Arg  
               
               
                     210                 215                 220  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 12  
               
               
                 &lt;211&gt; LENGTH: 476  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 12  
               
               
                   
               
               
                 Met Phe Asp Leu Arg Arg Ser Asp Val Ala Leu Leu Gln Ala Val Ala  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Asp His Gly Ser Leu His Ala Ala Gln Arg Gln Gly Trp Val Thr Gln  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Ser Ser Ala Ser Arg Arg Leu Thr Arg Leu Glu Arg Arg Leu Arg Thr  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Val Leu Val Ser Arg Gly Ser Thr Gly Ala Arg Leu Thr Asp Glu Gly  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 His Ala Leu Leu His Ala Gly Gln Arg Leu Leu Gly Ala Ile Asp Phe  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Ala Met Ala Asn Ala Ala Asp Thr Asp Glu Pro Gly Pro Arg Leu Arg  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Val Leu Gln Met Ala Val Ser Thr Glu Tyr Thr Cys Glu Ala Gly Glu  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Glu Pro Ala Val Gly Phe Pro Asp Val Val Phe Asp Leu Val Pro Ala  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Ala Arg Gln Asp Val Trp Ser Arg Phe Asp Arg Tyr Ala Val Asp Ala  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Ala Cys Gly Trp Ala Arg Ser Thr Pro Ala Leu Arg Arg Tyr Gly Ala  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Asp Val Arg Leu Val Val Glu Glu Pro Gln Trp Val Ala Val Pro Arg  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Gly His Pro Leu Ala Gly Arg Gly Ala Leu Gly Leu Glu Asp Leu Ala  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Glu Ala Glu Trp Val Ala Ile Val Gly Glu Ser Thr His Glu Asp Leu  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Ala Arg Ala Phe Ala Arg His Gly Leu Thr Pro Arg Val Gly Cys Thr  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Val His Ser Arg Ser Ala Ala Ala Asp Leu Val Ala Arg Gly Tyr Gly  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Phe Ala Leu Val Ser Pro Leu Cys Ala Ala Pro Val Glu Asp Ala Gly  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Tyr Ala Leu Arg Pro Leu Arg Gln Gln Val Val Arg Arg Leu Phe Leu  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Ala Thr Asp Pro Leu Leu Leu Pro Glu Ala Leu Ala Arg Asp Leu Cys  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Thr Gly Leu Gln Arg Arg Tyr Val Gln His Ala Ala Glu Arg Asn Pro  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Gly Tyr Leu Arg Ser Thr Thr Phe Pro Leu Pro Ala Ala Asp Leu Ser  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Ala Pro Pro Pro Gly Arg Ser Ala Ala Thr Glu Pro Asp Gly Pro Arg  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Asp Pro Leu Pro Phe Leu Val Cys Glu Arg His Trp Thr Ala Glu Gly  
               
               
                             340                 345                 350  
               
               
                   
               
               
                 Pro Ser Ser Leu Val Glu Ala Glu His Leu Tyr Leu Leu Arg Val Ile  
               
               
                         355                 360                 365  
               
               
                   
               
               
                 Glu Arg Thr Gly Ser Leu Asn Arg Ala Ala Ser Asp Leu Leu Ile Thr  
               
               
                     370                 375                 380  
               
               
                   
               
               
                 Gln Pro Ala Leu Thr Arg Arg Ile His Arg Leu Glu Gln Val Cys Gly  
               
               
                 385                 390                 395                 400  
               
               
                   
               
               
                 Arg Thr Leu Val His Ser Ala Pro Arg Gly Thr Cys Leu Ser Pro Met  
               
               
                                 405                 410                 415  
               
               
                   
               
               
                 Ala Arg Arg Leu Leu His Cys Thr Glu Ala Ala Glu Asp Arg Leu Asp  
               
               
                             420                 425                 430  
               
               
                   
               
               
                 Thr Leu Val Ala Ala Leu Arg Arg Ala Ala Ala Ser Thr Thr Pro Pro  
               
               
                         435                 440                 445  
               
               
                   
               
               
                 Leu Pro Arg Gln Arg Pro Ala Gly Ser Gly Glu Thr Ser Lys Asn Arg  
               
               
                     450                 455                 460  
               
               
                   
               
               
                 Ala Ser Ser Leu Leu Leu Ser Ser Thr Glu Val Cys  
               
               
                 465                 470                 475  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 13  
               
               
                 &lt;211&gt; LENGTH: 483  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 13  
               
               
                   
               
               
                 Val Ser Ala Pro Ala His Gly Ser Pro Ala Arg Gly Ala Ser Thr Val  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Ala Leu Ala Val Leu Ala Ser Ala Cys Gly Leu Phe Ala Leu Met Gln  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Leu Ala Val Thr Met Leu Leu Thr Gln Leu Arg His Gly Phe Gly Val  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Gly Ala Ala Asp Thr Gly Trp Val Val Ser Gly His Leu Leu Val Ala  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Cys Val Ala Thr Pro Val Val Gly Arg Leu Gly Asp Leu Tyr Gly Arg  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Arg Arg Val Leu Leu Ala Val Leu Ala Val Phe Ala Ala Gly Gly Ala  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Val Ala Ala Ser Ala Asp Thr Phe Gly Leu Leu Leu Ala Ala Arg Leu  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Val Met Gly Val Ala Gly Gly Leu Phe Pro Leu Ala Val Gly Leu Val  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Arg Glu Gly Phe Pro Ala Gly Ala Leu Ala Gly Pro Phe Gly Val Leu  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Ser Ala Ser Phe Gly Val Gly Gly Gly Ala Gly Ile Met Leu Ala Gly  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Val Val Glu Gly Asp Pro Asp Gly Tyr Arg Trp Val Phe Ala Thr Gly  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Ala Ala Leu Ala Ala Leu Leu Leu Leu Ile Gly Ala Ala Val Leu Pro  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Glu Thr Pro Arg Arg Ala Gly Gln Arg Leu Asp Ala Pro Gly Leu Thr  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Leu Leu Ala Val Ser Ser Ala Leu Val Leu Leu Ala Leu Gly Arg Tyr  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Gly Arg Asp Gly Ile Gly Ser Val Thr Gly Ser Thr Leu Leu Ala Gly  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Ala Val Val Ser Gly Ala Ala Leu Leu Ala Trp Glu Arg Arg Thr Thr  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Thr Pro Met Met Asp Leu Arg Leu Met Ser Arg Arg Pro Ile Trp Thr  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Leu Asn Ala Val Ser Leu Leu Thr Gly Leu Val Met Phe Val Thr Gly  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Thr Phe Pro Pro Ala Ile Ala Glu Ala Pro Arg Ser Ala Gly Gly Leu  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Gly Val Ala Gly Leu Gly Val Ile Val Val Met Met Pro Met Glu Ile  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Gly Thr Leu Gly Gly Gly Leu Leu Ser Gly Arg Leu Gly Arg Val Leu  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Pro Pro Arg Ala Val Met Val Thr Gly Thr Val Leu Phe Ala Ala Ser  
               
               
                             340                 345                 350  
               
               
                   
               
               
                 Ala Val Val Phe Ala Phe Leu Pro Val Ser Met Ala Ser Leu Ala Leu  
               
               
                         355                 360                 365  
               
               
                   
               
               
                 Gly Thr Leu Leu Asn Gly Ala Ala Thr Gly Val Leu Gly Gly Ala Met  
               
               
                     370                 375                 380  
               
               
                   
               
               
                 Thr Glu Leu Ile Thr Leu Ala Ser Pro Gly Gly Thr Thr Gly Val Val  
               
               
                 385                 390                 395                 400  
               
               
                   
               
               
                 Val Gly Thr Asn Ser Leu Leu Arg Ser Leu Gly Gly Ser Phe Gly Val  
               
               
                                 405                 410                 415  
               
               
                   
               
               
                 Gln Ala Gly Ser Met Val Leu Ala Ala Gly Thr Thr Gly Asp His Pro  
               
               
                             420                 425                 430  
               
               
                   
               
               
                 Ser Pro Ala Ala Tyr Thr Leu Val Phe Ala Gly Thr Ala Val Leu Gly  
               
               
                         435                 440                 445  
               
               
                   
               
               
                 Ala Leu Gly Ile Cys Ala Gly Ser Ala Phe Pro Arg Ala Ala Arg Ser  
               
               
                     450                 455                 460  
               
               
                   
               
               
                 Asn Gly His Thr Thr Gly Thr Asn Pro Pro Thr Ala Gly Thr Val Asp  
               
               
                 465                 470                 475                 480  
               
               
                   
               
               
                 Arg Leu Thr  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 14  
               
               
                 &lt;211&gt; LENGTH: 681  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 14  
               
               
                   
               
               
                 Met Thr Val Pro Ala Ala Arg Ser Gly Arg Lys Val Tyr Phe Ile Gly  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Leu Asn Ala Val Pro Phe Leu Pro Leu Val Ala Gly Leu Leu Arg Thr  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Tyr Ala Glu Gln Asp Pro Arg Val Ala Ala Gly Tyr Asp Phe Gln Glu  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Pro Val Phe Leu Val Asp Gly Val Gln Glu Met Ala Ala Gly Ile Thr  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Asp Pro Asp Val Leu Ala Leu Ser Cys Tyr Val Trp Asn Phe Arg Arg  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Gln Met Lys Val Ala Arg Leu Val Lys Glu Arg His Pro Gly Met Leu  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Val Val Ala Gly Gly Pro His Val Pro Asp Arg Pro Gly Asp Phe Phe  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Ala Arg His Pro Tyr Val Asp Val Leu Val His Gly Glu Gly Glu Thr  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Ala Phe Arg Glu Leu Leu Ile Glu Arg Leu Ala Asp His Pro Asp Tyr  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Thr Arg Val Pro Gly Val Ser Val Arg His Gly Thr Glu Ala Val Pro  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Gly Arg Pro Ala Glu Arg Leu Pro Arg Arg Ile Glu Thr Pro Ser Pro  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Tyr Leu Leu Gly Val Met Asp Gly Ala Val Ala Thr Cys Arg Gln Arg  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Asp Leu Arg Phe Tyr Ala Leu Trp Glu Thr Asn Arg Gly Cys Pro Tyr  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Ser Cys Ala Phe Cys Asp Trp Gly Ser Ala Thr Met Ser Ala Leu Arg  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Leu Phe Asp Ala Glu Arg Leu Gln Glu Glu Ile Glu Trp Phe Ala Glu  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 His Asp Val Glu Asp Leu Phe Val Cys Asp Ala Asn Phe Gly Ile Leu  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Pro Arg Asp Leu Glu Ile Ala Arg Ala Leu Ala Asp Ala Arg Ala Ala  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Thr Gly Ala Pro Lys Leu Ile Arg Val Asn Phe Ala Lys Asn Ser Asn  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Asp Arg Val Phe Glu Ile Ser Lys Thr Trp His Asp Ala Asp Leu Leu  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Met Gly Thr Thr Leu Ser Met Gln Ser Thr Asp Leu Asp Val Leu Glu  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Ala Ile Asp Arg Lys Asn Ile Gly Leu Glu Asn Tyr Arg Lys Leu Gln  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Gln Arg Tyr Ala Thr Glu Asn Ile His Thr Tyr Thr Glu Leu Ile Leu  
               
               
                             340                 345                 350  
               
               
                   
               
               
                 Gly Leu Pro Leu Glu Ser Pro Arg Ser Phe Arg Asp Gly Ile Gly Ser  
               
               
                         355                 360                 365  
               
               
                   
               
               
                 Leu Leu Glu Ala Gly Asn His Glu Asp Ile Arg Val Tyr Glu Phe Gly  
               
               
                     370                 375                 380  
               
               
                   
               
               
                 Ile Leu Pro Asn Ala Pro Ile Asn Thr Pro Glu Lys Ile Ala Gly Tyr  
               
               
                 385                 390                 395                 400  
               
               
                   
               
               
                 Gly Leu Arg Thr Val Pro Lys Arg Leu Tyr Val Glu Glu Pro Gly Thr  
               
               
                                 405                 410                 415  
               
               
                   
               
               
                 Pro Asp Asp Glu Ala Glu Thr Val Asp Met Val Met Glu Thr Asn Ala  
               
               
                             420                 425                 430  
               
               
                   
               
               
                 Met Ser Arg Asp Glu Trp Val Asp Cys Phe Gly Phe Val Gln Ala Val  
               
               
                         435                 440                 445  
               
               
                   
               
               
                 Gln Phe Leu His Asn Gly Cys Tyr Thr Arg Tyr Leu Ser Met Tyr Leu  
               
               
                     450                 455                 460  
               
               
                   
               
               
                 Arg Gln Arg His Asp Ile Gly Tyr Thr Ala Phe Tyr Glu Arg Leu Gln  
               
               
                 465                 470                 475                 480  
               
               
                   
               
               
                 Gln Tyr Phe Gly Ala Arg Pro Asp Thr Val Leu Gly Ser Ile Tyr Leu  
               
               
                                 485                 490                 495  
               
               
                   
               
               
                 Arg Met Arg Lys Leu Tyr His Asp Tyr Ile Asp Ile Pro Glu Leu Pro  
               
               
                             500                 505                 510  
               
               
                   
               
               
                 Leu Ala Asn Leu Val Ala Ser Gln Pro Asp Met Ala Ala Asp Leu Ala  
               
               
                         515                 520                 525  
               
               
                   
               
               
                 Arg Tyr Gly Lys Arg Arg Gly Trp Thr Ile Asp Asn Trp Gly Trp Leu  
               
               
                     530                 535                 540  
               
               
                   
               
               
                 Arg Ile Ala Asn Asp Phe Glu Arg Thr Tyr Thr Glu Leu Arg Asp Phe  
               
               
                 545                 550                 555                 560  
               
               
                   
               
               
                 Val Ala Ala Leu Gly Val Asp Asp Thr Ser Asp Pro Asp Leu Ala Glu  
               
               
                                 565                 570                 575  
               
               
                   
               
               
                 Val Phe Arg Phe Gln Gln Asp Val Met Leu Arg Pro Asp Tyr Asp Pro  
               
               
                             580                 585                 590  
               
               
                   
               
               
                 Ala Ala Gly Arg Thr Thr Glu Tyr Thr Ala Asp Trp Pro Gly Tyr Phe  
               
               
                         595                 600                 605  
               
               
                   
               
               
                 Thr Thr Gly Glu Leu Arg Arg Arg Pro Val Arg Met Arg Leu Ala Asp  
               
               
                     610                 615                 620  
               
               
                   
               
               
                 Gln Arg Phe Gly Ala Asn Gly Arg Tyr Thr Pro Val Pro Gly Asp Leu  
               
               
                 625                 630                 635                 640  
               
               
                   
               
               
                 Lys Ala Phe Ala Arg Ala Ala Ile Gly Pro Ser Tyr Pro Val Ser Arg  
               
               
                                 645                 650                 655  
               
               
                   
               
               
                 Ile Gly His Tyr Arg His Arg Phe Glu Ala Ala Glu Val Thr Ser Pro  
               
               
                             660                 665                 670  
               
               
                   
               
               
                 Ala Glu Pro Val Leu Thr Glu Gln Arg  
               
               
                         675                 680  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 15  
               
               
                 &lt;211&gt; LENGTH: 474  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 15  
               
               
                   
               
               
                 Met Arg Val Leu Leu Val Trp Pro Arg Asn Glu Arg Ala Leu Leu Ser  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Asp Arg Leu Ser Cys Cys Glu Pro Leu Pro Leu Glu Tyr Leu Ala Gly  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Ala Leu Arg Gly Ala His Asp Val Thr Ile His Asp Leu Arg Val Asp  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Thr Ser Leu Glu Glu Tyr Ala Ala Thr His Glu Ala Pro Asp Leu Ile  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Gly Val Ala Ile Pro Tyr Thr Thr Ser Val Arg Val Ser Arg Asp Val  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Thr His Gln Ala Arg Arg Leu Trp Pro Gly Thr Pro Ile Val Leu Gly  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Gly His His Pro Thr Val Ser Ala Glu Trp Leu Thr Gly Phe Ala Ala  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Asp Trp Ile Val Ala Gly Glu Gly Gly Gly Pro Leu Ala His Leu Ala  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Ala Glu Leu Glu Ala Gly Arg Thr Pro Ala Pro Val Arg Gly Leu Ala  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Pro Tyr Asp Ala Arg Thr Gly Leu Glu Arg Asp Arg Arg Pro Lys Pro  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Ser Ala Leu Asp Asp Leu Pro Met Pro Asp Arg Thr Arg Leu Ala His  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 His Arg Gly Arg Tyr Phe His Ser Ile Tyr Arg Pro Val Ala Leu Ile  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Arg Phe Thr Ala Gly Cys Pro Tyr Thr Cys Lys Phe Cys Ser Leu Trp  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Arg Met Thr Asp Arg Arg Tyr Leu Val Lys Asp Ile Asp Arg Val Leu  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Ala Glu Ile Ala Asp Ile Asp Gly Asp Asn Leu Tyr Val Val Asp Asp  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Glu Ala Phe Ile Gln Pro Val Arg Met Leu Glu Leu Ala Asp Ala Ile  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Asp Lys Ala Gly Phe Arg Lys Lys Phe His Met Tyr Val Arg Thr Asp  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Thr Ala Leu Arg Arg Pro Asp Val Ile Ala Arg Trp Ala Glu Ile Gly  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Leu Asp Ser Val Leu Val Gly Ala Glu Ser Met Thr Asp Glu Glu Leu  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Thr Gly Tyr Arg Lys Gly Thr Asp Pro Gly Gln Thr Arg Arg Ala Leu  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Asp Leu Phe His Gly Asn Gly Val Lys Val Arg Ala Asn Phe Ile Val  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Gln Pro Asp Trp Ser Glu Ala Asp Phe Ala Arg Leu Gly Arg Thr Val  
               
               
                             340                 345                 350  
               
               
                   
               
               
                 Asp Glu Leu Gln Val Asp Met Pro Ser Phe Ser Val Leu Thr Pro Leu  
               
               
                         355                 360                 365  
               
               
                   
               
               
                 Pro Gly Thr Asp Leu Tyr Asp Glu Ala Lys Leu Gly Leu Ile Ser Asp  
               
               
                     370                 375                 380  
               
               
                   
               
               
                 Asn Pro Glu Leu Phe Asp Cys Tyr His Ser Leu Phe Arg Thr Arg Leu  
               
               
                 385                 390                 395                 400  
               
               
                   
               
               
                 Pro Leu Glu Arg Phe Tyr Gly Glu Leu Ala Asp Leu Leu Ala Gly Ala  
               
               
                                 405                 410                 415  
               
               
                   
               
               
                 Ser Ala Arg Thr Ala Pro Gly Val Thr Gly Glu Ser Asp Pro Ser Val  
               
               
                             420                 425                 430  
               
               
                   
               
               
                 Phe Tyr Tyr Ser Asp Asp Asp Ala Phe Asp Gln Met Leu Arg Glu Leu  
               
               
                         435                 440                 445  
               
               
                   
               
               
                 Arg Arg Gly Ala Asp Trp Ser His Pro Arg Glu Ser Trp Ser Pro Thr  
               
               
                     450                 455                 460  
               
               
                   
               
               
                 Arg Glu Pro Glu Thr Val Ala Gly Thr Gly  
               
               
                 465                 470  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 16  
               
               
                 &lt;211&gt; LENGTH: 458  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 16  
               
               
                   
               
               
                 Met Ala Gly Phe Leu Leu Arg Cys Arg Pro Glu Gly Ala Val Pro Gln  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 His Leu Gly Ala Gly Thr Gly Leu Ala Thr Glu Val Thr Arg Asp Gly  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Ala Asp Val Leu Val Val His Gly Asp Pro Leu Thr Pro Gly Gly Gln  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Ala Pro Ile His Ala Pro Leu Asp Glu Leu Ile Ala Trp Thr Val Arg  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Ala Tyr Ser Arg Phe Cys Ala Val Leu Val Arg Asp Asp Arg Ala Val  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Leu Trp Ser Asp Asn Gly Ala Thr Cys Pro Leu His Tyr Ala Arg Gly  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Ala Asp Asp Thr Leu Leu Val Ala Thr Ser Ala Gly Ala Leu Leu Pro  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Leu Leu Gly Thr Ala Pro Val Leu Gly Glu Gly Asp Arg Ala Val Leu  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Pro Gly Gly Arg Phe Ala Gly Val Thr Ala Val Pro Ala Gly Thr Ala  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Val Thr Leu Ala Val Ala Gly Phe Asp Thr Glu Pro Leu Leu Thr Arg  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Arg Tyr His Arg Leu Pro Ala Arg Pro Thr Glu Thr Asp Pro Glu Arg  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Ala Val Thr Ala Val Arg Asp Ala Leu Thr His Ala Val Gly Arg Leu  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Ala Thr Gly Leu Thr Glu Ala Gly Val Met Leu Ser Gly Gly Val Asp  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Ser Ser Ser Val Ala Ala Leu Ala Ala Arg Glu Val Thr Ser Leu Ser  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Thr Tyr Thr Val Gly Thr Pro Phe Gly Asp Glu Phe Ala Gln Ala Ala  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Trp Phe Ala Glu Arg Leu Gly Ser Lys His His Glu Leu Val Phe Glu  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Pro Glu Gln Leu Thr Ala Leu Leu Pro Glu Met Ile Arg Ser Leu Glu  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Thr Trp Asp Leu Leu Thr Leu Gln Ile Ala Ala Pro Ala Cys Phe Leu  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Leu Gly His Ile Ala Thr Gly Ala Arg Gln Val Met Leu Ser Gly Tyr  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Gly Ala Asp Leu Ile Phe Ala Gly Leu Gly Gly Thr Gly Thr Glu Thr  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Arg Ile Glu Arg Ser Val Ala Ala Gln Thr Ala Ala Thr Ala Val Ser  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Asn Glu Phe Asn Pro Ala Tyr Ala Asp Ala Arg Asp Val Val Val Arg  
               
               
                             340                 345                 350  
               
               
                   
               
               
                 Tyr Pro Tyr Trp Thr Arg Glu Val Met Ser Thr Ala Leu Gly Ile Arg  
               
               
                         355                 360                 365  
               
               
                   
               
               
                 Gly Arg Leu Lys Val Arg Pro Asp Thr Ala Lys Trp Val Leu Arg Ser  
               
               
                     370                 375                 380  
               
               
                   
               
               
                 Ala Val Thr Gly Ile Leu Pro Asp Glu Val Ala Trp Arg Pro Lys Arg  
               
               
                 385                 390                 395                 400  
               
               
                   
               
               
                 Gly Ile His Glu Gly Thr Ala Met Ser Arg Met Phe Ala Ala Ala Leu  
               
               
                                 405                 410                 415  
               
               
                   
               
               
                 Gly Ser Asp Asp Arg His Thr Gln Ala Arg Arg Leu Tyr Glu Met Ala  
               
               
                             420                 425                 430  
               
               
                   
               
               
                 Thr Glu Val Phe Arg Asp Thr Ala Ala Gly Thr Asp Glu Leu Glu Gly  
               
               
                         435                 440                 445  
               
               
                   
               
               
                 Ser Asp Glu Gly Leu Ala Gly Val Ala Ser  
               
               
                     450                 455  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 17  
               
               
                 &lt;211&gt; LENGTH: 367  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 17  
               
               
                   
               
               
                 Met Pro Ser Pro Ser Lys Leu Arg Pro Ile Thr Asp Glu Asp Val Arg  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Arg Ala Val Arg Leu His Phe Asp Pro Gln Asp Gly Thr Pro Tyr Trp  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Leu Glu Arg Asp Arg Arg Asp Gly Thr Asp Ala Leu Arg Lys Val His  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Gly Met Leu Asp Ala Gln Gln Leu Ile Gly Leu Arg Asp Gly Pro Asp  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Gln Ala His Phe Glu Glu Ala Ser Arg Arg Thr Pro Leu Ala Asn Phe  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Val Pro Arg Arg Val Leu Thr Glu Gly Gly Pro Leu Trp Ala Ala Gln  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Thr Gly Gly Thr Thr Gly Pro Ala Lys His Gly Thr Trp Gly Ala Arg  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Tyr Trp Ala Asp Ile Leu Glu Phe Ser Asp Glu Phe Leu Asp Leu His  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Gly Val Pro Arg Gly Val Asp Trp Leu Phe Val Gly Pro Met Gly Pro  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 His Thr Thr Gly Arg Leu Val Val Ala Phe Ala Glu Arg Arg Gly Gly  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Met Cys Phe Ser Val Asp Leu Asp Pro Arg Ile Val Lys Ile Phe Gly  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Glu Glu Gly Met Thr Ala Ala Tyr Asp Arg Tyr Val Gln His Ile Trp  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Asp Gln Val Ala Glu Val Ala Arg Ala Gln Arg Ile Gly Val Leu Phe  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Cys Thr Ser Arg Leu Leu Glu Met Leu Pro Glu Arg Leu Gly Thr Glu  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Ala Leu Pro Gly Leu Arg Ala Ile Val His Ala Gly Thr Thr Met Glu  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Pro Glu Ser His Arg Gln Leu Arg Glu Asp Phe Phe Pro Gly Val Pro  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Val Val Gly Met Tyr Gly Thr Ser Thr Thr Gly Ile Ser Trp Gln Lys  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Pro Phe Glu Pro Glu Asp Asp His His Val Val Tyr Val Pro Cys Gln  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Pro His Ile Ala Leu Asp Ala Val Asp Asp Asp Gly Asn Glu Val Pro  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Phe Gly Glu Glu Gly Arg Val Arg Val Trp Arg Leu Thr Asp Asp Ala  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Leu Leu Pro Gly Phe Leu Glu Arg Asp Arg Ala Arg Arg Val Gln Pro  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Tyr Gly Ala Ala Ala Glu Arg Tyr Pro Trp Pro Trp Leu Gly Asp Pro  
               
               
                             340                 345                 350  
               
               
                   
               
               
                 Tyr Ser Pro Glu Phe Thr Glu Gly Arg Arg Ile Glu Gly Val Tyr  
               
               
                         355                 360                 365  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 18  
               
               
                 &lt;211&gt; LENGTH: 472  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 18  
               
               
                   
               
               
                 Val Thr Thr Val Thr Thr Gly His Ala Gly Pro Gln Arg Ala Gly Ala  
               
               
                                   5                  10                  15  
               
               
                   
               
               
                 Val Leu Asp Val Pro Ala Tyr Ala Gly Arg Arg Pro Val Met Ser Ser  
               
               
                              20                  25                  30  
               
               
                   
               
               
                 Arg Pro Ala Ala Leu Thr Gly Thr Thr Gly Glu Thr Val Ala Arg Val  
               
               
                          35                  40                  45  
               
               
                   
               
               
                 Gly Ala Ala Gly Arg Leu Val Gln Phe Gln Met Ala Gln Glu Ala Ala  
               
               
                      50                  55                  60  
               
               
                   
               
               
                 Ala Val Ala Arg Arg Leu Arg Ala Thr Asp Asp Asp Ala Trp Phe Ala  
               
               
                  65                  70                  75                  80  
               
               
                   
               
               
                 Leu Leu Arg Arg Ala Ala Asp Thr Leu Thr Ala Arg Val Ala Asp Gly  
               
               
                                  85                  90                  95  
               
               
                   
               
               
                 Thr Ala Gln Pro Trp Leu Thr Ala Leu Ser Ala Ala Ser Gly Leu Pro  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Pro Arg Arg Ala Ala Arg Gly Ile Glu Thr Val Ala Ala Asp Leu Ala  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Arg Met Asp Glu Ile Leu Ala Ala Gln Ser Pro Asp Gly Thr Val Ala  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Ala Tyr Arg Thr Gly Gly His His Pro Arg Trp Ser Trp Arg Pro Ala  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Gly Arg Ser Val Leu Val Lys Val Ala Asp Asn Phe Pro Thr Ile Asn  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Ile Glu Trp Leu Gln Ala Leu Ala Ala Arg Arg Pro Val Leu Leu Ser  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Thr Ser Arg His Asp Pro Phe Thr Pro Val Leu Leu Thr Glu Ala Leu  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Tyr Glu Ala Gly Leu Pro Glu His Ala Val Ser Val Val His Gly Asp  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Ala Pro Ala Leu Arg Arg Leu Ala Asp Gln Val Leu Trp Pro Gly Glu  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Asp Val Pro Ala Asp Leu Pro Pro Gly Lys Ala Lys Thr Tyr His Phe  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Gly Arg Ser Arg Ala Val Val Gly Ala Gly Ala Ala Asp Asp Ala Trp  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Pro Arg Leu Ala Arg Ala Ala Phe Ala Gly Cys Gly Arg Leu Cys Thr  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Asn Val Ser Ser Val Ile Ala Leu Gly Asp Ala Arg Gln Ala Ala Asp  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Arg Leu Ala Glu Glu Phe Ala Thr Arg Pro Val Leu Pro Leu Asp Asp  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Pro Ala Ala Thr Val Pro Ala Phe Pro Asp Arg Ala Arg Arg Asp Ala  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Leu Ala Thr Arg Ile Glu Arg Glu Ile Ala Ala Gly Ala Val Asp Val  
               
               
                             340                 345                 350  
               
               
                   
               
               
                 Thr Glu Ala Val Thr Gly Val Pro Leu Arg Val Glu Val Asp Gly Ala  
               
               
                         355                 360                 365  
               
               
                   
               
               
                 Ala Phe Leu Arg Pro Thr Val Leu Leu Val Asp Pro Gly Ser Pro Leu  
               
               
                     370                 375                 380  
               
               
                   
               
               
                 Phe Gly Thr Glu Leu Pro Phe Pro Phe Thr Ala Val Ala His Val Pro  
               
               
                 385                 390                 395                 400  
               
               
                   
               
               
                 Arg Ser Lys Ala Val Ala Ala Cys Ala Gly Ser Leu Ile Val Ser Val  
               
               
                                 405                 410                 415  
               
               
                   
               
               
                 Leu Gly Asp Ala Ala Gly Leu Leu Gly Ala Leu Ala Glu Glu Pro Gly  
               
               
                             420                 425                 430  
               
               
                   
               
               
                 Val Asp Lys Val Phe Gly Ala Glu Glu Tyr Asp Arg Gly Tyr His Pro  
               
               
                         435                 440                 445  
               
               
                   
               
               
                 Cys Asp Pro His Glu Gly Tyr Leu Ala Asp Phe Leu Phe Arg Lys Lys  
               
               
                     450                 455                 460  
               
               
                   
               
               
                 Ala Val Ile Pro Gly Ala Ala Gly  
               
               
                 465                 470  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 19  
               
               
                 &lt;211&gt; LENGTH: 484  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 19  
               
               
                   
               
               
                 Met Gln Val Leu Leu Val Asn Ala Arg Arg Ser Pro Tyr Ser Gly Glu  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Ser Ile Ser Ala Pro Gln Leu Gly Leu Leu Ser Leu Ala Ser Val Leu  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Arg Glu Gly Thr Phe His Asp Thr Ala Gly Thr Asp Val His Phe Ile  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Asp Asp Gln Leu Phe Val Leu Gln Arg Pro Leu Ser Thr Pro Ser Glu  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Phe Leu Arg Gly Tyr Arg Pro Asp Ile Val Gly Ile Gln Val Leu Thr  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Ser Ser Leu Lys Asn Gly Ile Lys Leu Ala Ser Glu Val Arg His Arg  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 His Pro Asn Ala Leu Thr Val Leu Gly Gly Val Gly Ala Ser Pro Ile  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Ala Arg Lys Leu Ile Glu Glu Asn Ala Ala Asp Val Val Val Arg Gly  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Glu Gly Glu Tyr Ser Phe Ser Gln Leu Val His Glu Phe Gly Lys Asn  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Gly Arg Lys Asn Phe Ala Lys Val Arg Gly Ile Thr Phe Arg Asp Asp  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Glu Gly Glu Val Val Glu Thr Pro Ala Ala Pro Gln Val Val Asn Leu  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Asp Lys Leu Pro Lys Pro Ala Arg Asp Leu Ala Asp Leu Asp Leu Tyr  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Arg Arg Ile Ser Arg Gly Arg Ser Gly Asn Leu Val Thr Ser Arg Gly  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Cys Ser Tyr Ala Cys Ala Tyr Cys Tyr Ser Lys His Gln Trp Gly Val  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Gly Gln Arg Arg His Ser Ala Ala Arg Val Val Asp Glu Ile Arg Glu  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Leu Val Glu Val Tyr Gly Phe Asp Arg Ile Arg Ile Glu Asp Asp Asp  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Phe Val Glu Asp Val Pro Arg Met Gln Glu Leu Cys Asp Gly Ile Ala  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Lys Ser Gly Leu Gln Gly Lys Phe Glu Trp Glu Ala Lys Ala Arg Pro  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Asp Leu Ile Asn Asp Asp Met Ala Arg Met Leu Arg Glu Ser Gly Cys  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Phe Arg Leu Leu Val Gly Val Glu Thr Leu Ser Trp Asn Leu Leu Lys  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Arg Leu Gly Arg Pro Val Lys Val Asp Val Thr Glu Arg Ala Ile Ser  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Cys Leu Thr Asn Asn Gly Ile Gly Val Gln Ala Thr Met Ile Leu Gly  
               
               
                             340                 345                 350  
               
               
                   
               
               
                 Ile Pro Gly Glu Thr Asp Glu Ala Met Arg Thr Thr Ile Thr Trp Leu  
               
               
                         355                 360                 365  
               
               
                   
               
               
                 Gln Ala Arg Leu Gly Lys Asn Lys His Asp Leu Val Ser Pro Cys Phe  
               
               
                     370                 375                 380  
               
               
                   
               
               
                 Phe Val Pro Phe His Gln Glu Val Glu Lys Asp Met Ala Lys Arg Val  
               
               
                 385                 390                 395                 400  
               
               
                   
               
               
                 Asp Phe Thr Val Glu Thr Ser Asp Thr Asp Cys Tyr Thr Gly His Ile  
               
               
                                 405                 410                 415  
               
               
                   
               
               
                 Pro Val Thr Ser Ser Met Gly Ala Ser Ile Asp Glu Leu Trp Lys Leu  
               
               
                             420                 425                 430  
               
               
                   
               
               
                 Tyr Asp Asp Met Thr Pro Ser Arg Ser Gln Gly Gln Tyr Lys Arg Ile  
               
               
                         435                 440                 445  
               
               
                   
               
               
                 Ala Phe Leu Ala Asn Leu Gln Thr Val Gln Thr Arg Leu Gly Leu Leu  
               
               
                     450                 455                 460  
               
               
                   
               
               
                 Asp Gly Asp Gly Ala Ser Asn Leu Ser Asn Glu Pro Ala Ala Leu Val  
               
               
                 465                 470                 475                 480  
               
               
                   
               
               
                 Pro Glu Val Gln  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 20  
               
               
                 &lt;211&gt; LENGTH: 259  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 20  
               
               
                   
               
               
                 Met Thr Ala Ser His Asp Thr Ala Asp Ala Thr Asp Arg Thr Val Gly  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Ser Thr Ser Gly Glu Arg Ala Ala Phe Ala Arg Asp Gly Val Val Arg  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Trp Gly Arg Leu Leu Thr Pro Asp Gln Ile Asp Ala Leu Arg Ser Ser  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Val Glu Arg Ala Phe Phe Arg Asp Gly His Pro Ala Asp Gly Val Arg  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Asp Leu Ser Glu Arg Gln Gly Arg Pro Leu Asp Leu Ala Leu Leu His  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Lys Ile Asn Leu Trp Arg Thr Asp Glu Ala Cys Ala Ala Gln Val Ala  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Arg Ala Asp Leu Ala Asp Arg Ala Glu Ala Leu Leu Gly Gly Pro Val  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Arg Leu Tyr Arg Asp His Val Phe Tyr Lys Pro Pro Gly Lys Gly Asp  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Arg Ser Arg Met Val Leu His Gln Asp Asn Arg Tyr Trp His Leu Asp  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Pro Pro Glu Ala Ile Thr Val Trp Met Ala Leu Asp Asp Ala Thr Val  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Glu Asn Gly Cys Val His Tyr Val Leu Gly Ser His Arg His Gly Arg  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Val Glu His Val Arg Pro Glu Glu Gly Ala Val Met Ile Glu Ala Arg  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Thr Glu Gln Glu Pro Val Ala Tyr Pro Ala Pro Ala Gly Asp Ala Leu  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Val His Ser Val Asn Thr Leu His Gly Ser Gly Pro Asn Leu Ser Asp  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Gly Pro Arg Arg Ala Tyr Val Val Val Tyr Val Arg Asp Gly Val Thr  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Met Arg Gly Glu Pro Met Thr Ser Phe Pro Leu Val Gly Asp Leu Val  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Arg Gly Gly  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 21  
               
               
                 &lt;211&gt; LENGTH: 240  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 21  
               
               
                   
               
               
                 Met Ala Asp Gly Pro Gly Ala Tyr Ala Asp Pro Val Asp Leu Asp Arg  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Val Tyr Pro Arg His Arg Thr Asp Val Pro Thr Trp Leu Thr Gly Leu  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Ala Arg Gln Ala Ala Asp Asp Ser Pro Pro Glu Leu Val Arg Tyr Leu  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Leu Asp Asp Pro Ala Arg Gly Arg Pro Ser Ala Val Leu Val Leu Phe  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Gly Thr Gly Asp Ala Gly Thr Asp Leu Leu Leu Val Arg Arg Ser Arg  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Thr Leu Arg Ser His Pro Asp Glu Val Cys Phe Pro Gly Gly Ser Val  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Ser Ala Gly Asp Arg Asp Val Val His Thr Ala Leu Arg Glu Ser Ala  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Glu Glu Thr Gly Leu Asp Pro Ala Gly Val Ala Val Ala Gly Thr Leu  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Arg Pro Leu Arg Ile Ala Trp Thr Asp Phe Arg Val Thr Pro Val Leu  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Gly Trp Trp Gly Ala Glu Ala Glu Pro Arg Gly Asp Arg Gly Glu Val  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Val Ser Val His Arg Val Pro Leu Ala Glu Phe Ala Asp Pro Ala Asn  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Arg Phe Arg Val Arg Tyr Gln Asp Gly Tyr Ile Ser Pro Gly Phe Leu  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Val Arg Glu Leu Phe Val Trp Gly Phe Thr Gly Ser Ile Val Asp Trp  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Leu Met Arg Leu Ala Gly Trp Gly Arg Pro Trp Asp Thr Ser Arg Ile  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Glu Glu Leu Pro Asp Ala Leu Arg Arg Tyr Gly Gly Gly Phe Gly Arg  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 22  
               
               
                 &lt;211&gt; LENGTH: 329  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 22  
               
               
                   
               
               
                 Met Gly Ser His Arg Leu Leu Arg Ala Arg Ala Gly Thr Ala Gly Ala  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Gly Pro Ser Arg Arg Gly Leu Ile Gly Thr Ser Leu Ala Gly Ile Ser  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Gly Leu Ala Ala Gly Phe Gly Ser Leu Gly Ala Arg Pro Ala Ala Ala  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Ala Arg Pro Gly Pro Val Gly Gly Thr Thr Arg Leu Arg Trp Phe Gly  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Thr Asn Ala Trp Glu Ile Gly Phe Gly Gly Arg Thr Val Leu Val Asp  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Pro Trp Leu Thr Arg Phe Thr Ala Gln Arg Pro Asp Gly Arg Val Asp  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Pro Asp Thr Pro Leu Thr Val Asp His Ser Ala Val Asp Arg His Leu  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Arg Ala Ala Asp Leu Ile Leu Leu Thr His Gly His Tyr Asp His Ile  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Gly Asp Leu Pro Tyr Val Met Arg Lys Phe Pro Ser Ala Pro Val Val  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Ala Thr Glu Thr His Ala His Leu Leu Thr Ala Met Gly Ala Pro Thr  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Asp Arg Val Ile Trp Ala Arg Gly Gly Glu Tyr Leu Asp Phe Gly Asp  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Phe Ala Val Arg Val Leu Pro Ser Leu His Ser Met Gly Pro Asp His  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Arg Tyr Phe Ala Pro Gly Thr Leu Thr Ala Pro Pro Arg Arg Ala Arg  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Thr Val Gly Asp Leu Leu Glu Gly Gly Thr Leu Ala Tyr His Ile Thr  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Ser Asp Ser Gly Ala Ser Val Val Asn Ile Gly Thr Ala Asn Val Ile  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Glu Arg Glu Leu Thr Gly Leu Arg Pro His Val Ala Ile Val Ala Val  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Pro Pro Cys Gly Ala Thr His Arg Tyr Leu Glu Arg Val Leu Thr Ala  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Leu Gly His Pro Pro His Val Ile Pro Thr His His Asp Gln Leu Asp  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Thr Pro Leu Phe Arg Pro Ala Ser Val Asp Pro Gly Gln Met Arg Ser  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Phe Arg Asp Gln Val Arg Ala Leu Gly Pro Gly Cys Ala Val Thr Glu  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Pro Gln Tyr Cys Asp Ala Phe Thr Leu  
               
               
                                 325  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 23  
               
               
                 &lt;211&gt; LENGTH: 399  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 23  
               
               
                   
               
               
                 Val Asp Pro Glu Ala Gly Ser Arg Ala Arg Gly Leu Lys Gly Val His  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Arg Val Ser Ala Asn Ser Gly Gly Ile Gly Gly Val Pro Gly Pro His  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Asn Gly Leu Thr Asp Val Pro Gly Val Arg Val Gly His Ala Gly Arg  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Thr Gly Asp Gly Trp Leu Thr Gly Val Thr Val Val Leu Ala Pro Pro  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Gly Gly Ala Val Ala Ala Val Asp Val Arg Gly Gly Gly Pro Gly Thr  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Arg Glu Thr Asp Ala Leu Asp Pro Arg Asn Leu Val Gln Thr Ile Asp  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Ala Val Val Leu Thr Gly Gly Ser Ala Phe Gly Leu Asp Ala Ala Gly  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Gly Val Ala Ala Trp Leu Glu Glu Gln Gly Arg Gly Phe Pro Val Gly  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Ala Asp Pro Ser Gln Val Val Pro Val Val Pro Ala Ala Ala Leu Phe  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Asp Leu Gly Arg Gly Gly Thr Trp Arg Ala Arg Pro Asp Ala Ala Leu  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Gly Arg Ala Ala Val Glu Ala Ala Ala Ala Arg Pro Glu Gly Asp Pro  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Val Glu Gln Gly Gly Val Gly Ala Gly Thr Gly Ala Val Val Gly Gly  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Leu Lys Gly Gly Ile Gly Thr Ala Ser Val Val Leu Asp Ser Gly Ala  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Thr Val Ala Ala Leu Ala Ala Val Asn Ala Ala Gly Ser Ala Val Asp  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Pro Ala Thr Gly Val Leu Tyr Gly Ala Arg Thr Gly Leu Pro Gly Glu  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Phe Ala Gly Tyr Gly Val Pro Asp Ala Ile Gly Ala Asp Thr His Ala  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Arg Ala Arg Ala Arg Leu Ala Glu Ala Ala Glu Glu Thr Ala Arg Arg  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Arg Ala Gly Gly Ala Ala Thr Leu Asn Thr Thr Leu Ala Val Val Ala  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Thr Asp Ala Thr Leu Thr Arg Ala Gln Ala Gln Lys Leu Ala Gly Thr  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Ala His Asp Gly Leu Ala Arg Ala Val Arg Pro Val His Leu Leu Ser  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Asp Gly Asp Thr Val Phe Ala Leu Ser Thr Gly Arg Arg Pro Leu Leu  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Pro Asp Arg Pro Asp Ala Thr Ala Ala Arg Ala Phe Gly Val His Leu  
               
               
                             340                 345                 350  
               
               
                   
               
               
                 Glu Ala Gly Ala Leu Asn Glu Val Leu Ala Ala Gly Ala Asp Val Leu  
               
               
                         355                 360                 365  
               
               
                   
               
               
                 Thr Arg Ala Val Val His Ala Val Leu Ala Ala Thr Gly Val Asp Thr  
               
               
                     370                 375                 380  
               
               
                   
               
               
                 Pro Gly Gly Val His Pro Ser Tyr Arg Glu Leu Tyr Ala Arg Pro  
               
               
                 385                 390                 395  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 24  
               
               
                 &lt;211&gt; LENGTH: 268  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 24  
               
               
                   
               
               
                 Met Asp Ala Asp Asp Cys Trp Ala Arg Ala Gly Thr Val Arg Ile Arg  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Leu Leu Gly Pro Val Glu Leu Ala Cys Gly Thr Arg Pro Val Pro Val  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Thr Gly Arg Arg Gln Leu Arg Val Val Ala Ala Leu Ala Leu Glu Ala  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Gly Arg Val Leu Ser Thr Ala Gly Leu Ile Ala Ser Leu Trp Ala Asp  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Glu Pro Pro Arg Thr Ala Ala Arg Gln Leu Gln Thr Ser Val Trp Met  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Ile Arg Arg Ala Leu Ala Ser Val Gly Ala Pro Gln Cys Val Val Arg  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Ser Thr Pro Ala Gly Tyr Leu Leu Asp Pro Ala His Tyr Glu Leu Asp  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Ser Asp Arg Phe Arg His Ala Val Leu Thr Ala Arg Glu Leu Gln Arg  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Asp Gly Arg Leu Ala Gln Ala Arg Ala Arg Val Asp Glu Gly Leu Ala  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Leu Trp Arg Gly Pro Ala Leu Gly Ala Ala Ala Gly Ala Gly Leu Gln  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Pro Arg Ala Arg Arg Leu Glu Glu Glu Arg Val Phe Ala Leu Glu Gln  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Arg Ala Gly Leu Asp Leu Ala Leu Gly Arg His Glu Thr Ala Ile Gly  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Glu Leu Leu Asp Leu Ile Ala Gln His Pro Leu Arg Glu Ala Ala Tyr  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Ala Asp Leu Met Leu Ala Leu Tyr Arg Ser Gly Arg Gln Ser Asp Ala  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Leu Ala Val Tyr Arg Arg Ala Gln Arg Val Leu Ala Asp Glu Leu Ala  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Val Arg Pro Gly Pro Arg Leu Ala Gly Leu Glu Arg Ala Ile Leu Arg  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Gln Asp Glu Ser Leu Leu Ala Gly Ala Ala Val Pro  
               
               
                             260                 265  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 25  
               
               
                 &lt;211&gt; LENGTH: 137  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 25  
               
               
                   
               
               
                 Met Thr Pro His Asp Ser Ala Ser Pro Thr Ala Thr Val Arg Leu Asp  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 His Thr Ala Val Tyr Ala Ser Asp Arg Tyr Leu Ser Ala Glu Phe Ile  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Ala Ala Ile Leu Gly Leu Glu Val Gly Lys Pro Phe Gly Pro Phe Leu  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Pro Val Asp Leu Gly Asn Gly Val Thr Leu Asp Tyr Tyr Glu Lys Arg  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Asp Glu Pro Ile Gln Ser Gln His Tyr Ala Phe Ile Val Pro Glu Asp  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Arg Phe Asp Ala Val Ile Asp Arg Leu Glu Thr Val Gly Val Thr Tyr  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Tyr Ala Asp Pro Ala His Thr Glu Pro Gly Arg Val Asn Gly Leu Phe  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Gly Gly Arg Gly Ala Tyr Phe Ala Asp Pro Asp Gly His Asn Met Glu  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Val Met Thr Arg Pro Tyr Val Arg Pro  
               
               
                     130                 135  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 26  
               
               
                 &lt;211&gt; LENGTH: 180  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 26  
               
               
                   
               
               
                 Val Arg Arg Val Ser Pro Ala Trp Ser Gly Val Arg Gly Arg His Val  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Arg Ser Ala Val Pro Ala Arg Arg Arg Ser Pro Val Thr Ser Ser Ala  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Gly Leu Pro Val Leu Ser Ser Leu Asp Asp Leu Ala Arg Leu Ala Asp  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Gly Ser Arg Gly Leu Tyr Val Arg Trp Ser Arg Gly Pro Arg Tyr Asp  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Leu Arg Glu Thr Gly Ser Ala Asp Ser Leu Thr Gly Ile Ser Leu Pro  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Gly Leu Ser Ala Asn Pro Leu Asp Val Asp Asp Trp Trp Ala Gly Arg  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Pro Leu Arg Leu Trp Val Ala Arg Arg Leu Tyr Asp Tyr Cys His Leu  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Arg His Asp Ile Gly Pro Gly Val Arg Pro Trp Val Leu Arg Gly Arg  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Glu Val Gly Arg Gly Pro Asp Asn Glu Pro Leu Leu Thr Asp Val Arg  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Pro Ile Ala Trp Ile Asp Pro Glu Val Ile His Glu Ala Arg Asp Glu  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Val Ala Arg Gln Arg Gly Asp Trp Gly Pro Leu Arg Arg Pro Pro Gln  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Ala Ser Gly Gly  
               
               
                             180  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 27  
               
               
                 &lt;211&gt; LENGTH: 62  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 27  
               
               
                   
               
               
                 Met Asn Thr Leu Ala Trp Trp Leu Arg Leu Thr Val Leu Ala Val Ala  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Gly Gly Ala Val Ala Leu Leu Val Gln His Trp Thr Asp Gly Arg Pro  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Trp Pro Glu Ala Gly Val Pro Ala Ala Leu Leu Val Val Val Ala Leu  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Leu Met Gly Val Val Ser Arg Arg Ser Arg Arg Asp Leu Trp  
               
               
                     50                  55                  60  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 28  
               
               
                 &lt;211&gt; LENGTH: 253  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 28  
               
               
                   
               
               
                 Met Thr Asn Arg Thr Ala Val Leu Ser Asp Ile His Gly Val Leu Pro  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Ala Leu Glu Ala Val Leu Ala Glu Pro Glu Val Arg Ala Ala Asp Arg  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Val Val Leu Thr Gly Asp Ile Ala Cys Gly Pro Gln Pro Ala Glu Val  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Leu Asp Leu Leu Thr Ala Leu Gly Asp Arg Val Thr Trp Val Ala Gly  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Asn Ala Asp Arg Glu Leu Val Glu Phe Arg Arg Gly Val Arg Glu Thr  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Ile Pro Asp Pro Ile Gly Pro Trp Ala Ala Arg Gln Leu Arg Pro Asp  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 His Leu Glu Leu Leu Ala Ser Leu Pro Leu Ser Val Arg Leu Pro Val  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Ala Gly Leu Gly Thr Val Leu Phe Cys His Ala Thr Pro Arg Asp Asp  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Glu Glu Val Val Val Val Asp Ser Arg Pro Asp Arg Trp Arg Glu Val  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Phe Asp Gly Leu Gly Pro Asp Val Asp Ala Val Ile Cys Gly His Thr  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 His Met Pro Phe Val Arg Leu Ala His Gly Arg Leu Val Val Asn Pro  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Gly Ser Val Gly Met Pro Tyr Gly Arg Ser Gly Ala His Trp Ala Leu  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Leu Gly Pro Gly Val Asp Leu Arg Arg Thr Pro Tyr Asp Thr Asp Ala  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Ala Ile Ala Arg Leu Thr Arg Asp Cys Gly Tyr Pro Ala Ile Ala Glu  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Trp Ala Asp Tyr Tyr Val Arg Ala Arg Ala Thr Asp Thr Glu Ala Leu  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Ala Ala Phe Gly Pro Arg Asp Gly Arg Gly Ala Glu Gly  
               
               
                                 245                 250  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 29  
               
               
                 &lt;211&gt; LENGTH: 61  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 29  
               
               
                   
               
               
                 Val Pro Cys Ala Pro Val Gly Pro Arg Thr Pro Ala Pro Pro Thr Ile  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Trp Pro Ala Pro Arg Gly Pro Arg Ala Thr Arg Arg Gly Gly Thr Ala  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Thr Ser Pro Arg Cys Ser Ser Thr Ile Cys Ser Ala Val Thr Trp Cys  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Ala Ala Arg Tyr Gly Ser Val His Gln Phe Arg Leu Gly  
               
               
                     50                  55                  60  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 30  
               
               
                 &lt;211&gt; LENGTH: 143  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 30  
               
               
                   
               
               
                 Met Pro Glu Ser Ile Glu Asp Pro Phe Thr Pro Pro Ser Pro Glu Gln  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Ala Arg Ala Glu Arg Val Ala Thr Ser Leu Phe Arg Ile Ala Glu Arg  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 His Ala Ala Thr Glu Glu Arg Arg Arg Arg Gln Thr His Pro Tyr Val  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Leu Ala Pro His Glu Ala Val Arg Leu Val Ala Phe Leu Leu Ser Gly  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Ala Ala Gln His Glu Glu Asp Glu Pro Glu Val Asp Arg Ala Asp Leu  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Leu Ala Ala Leu Thr Leu Leu Pro Ala Ala Arg Ala Asp Leu Asp Glu  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Ile Glu Ala Gly Leu Leu Lys Met Ala Arg Gly Arg Gly Leu Thr Trp  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Pro Glu Ile Ala Phe Gly Leu Gly Leu Gly Thr Pro Gln Ala Ala Arg  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Gln Arg Tyr Glu Arg Leu Ser Gly Arg Ile Ser Ala Asp Pro Glu  
               
               
                     130                 135                 140  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 31  
               
               
                 &lt;211&gt; LENGTH: 545  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Streptomyces cattleya  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 31  
               
               
                   
               
               
                 Met Phe His Arg Ile Ser Arg Pro Gly Arg Gly Leu Arg Asp Gly Ala  
               
               
                                 5                   10                  15  
               
               
                   
               
               
                 Gly Thr Val Thr Arg Gly Arg Arg His Arg Pro Val Arg Gly Pro Gly  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Glu Arg Ser Arg Cys Ser Arg Pro Ala Ser Ala Leu Ala Val Ala Leu  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Thr Leu Ala Leu Thr Ala Gly Val Val Ser Pro Ala Ile Ala Ala Thr  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Thr Pro Arg Ala Ala Pro Ser Ala Ala Pro Pro Pro Pro Ala Pro Thr  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Thr Ala Ala Gly Asp Val Leu Val Asn Gly Trp Gly Asp Gly Ala Gly  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Tyr His Leu Asp Val Ala Thr Gly Ser Gly Gly Tyr Asp Trp Arg Glu  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Leu Ala Val Leu Arg Pro Ala Gly Ile Asp Asp Ser Ser Trp Thr Gly  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Tyr Gln Cys Val Ser Gly Asp Gly Arg Tyr Ala Ala Val Ala Ile Leu  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Pro Ala Ser Ala Val Asn Leu Ala Val Ala Arg Asp His Gly Ala Phe  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Ala Tyr Ser Val Asp Leu Arg Ser Gly Ala Val Lys Pro Val Ala Ala  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Gly Val Ala Leu Lys Tyr His Thr Pro Gly Cys Gly Thr Gly Asp Thr  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Ala Glu Phe Thr Ile Asp Pro Gly Asn Asp Gln Arg Ala Thr Gln Val  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Leu Ser Ala Asp Leu Pro Ser Gly Arg Leu Thr His Val Thr Thr Val  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Pro Gly Gln Val Thr Ser Val Val Pro Ala Gly Asp Gly Pro Val Gly  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Val Leu Gly Gly Glu Leu Val Arg Ile Pro Glu Asp Gly Gly Arg Thr  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Ala Arg Pro Val Ala Leu Ala Ser Val Gly Gly Leu Ala Tyr Asp Leu  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Arg Pro Ala Ala Gly Gly Gly Val Asp Phe Ala Val Gln Arg Ala Ala  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Gly Arg Ser Ser Leu Ile Val Arg Glu Arg Ser Gly His Leu Thr Thr  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Leu Gly Glu Gly Thr His Thr Gly Leu Arg Leu Met Gln Gly Arg Ala  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Gly His Ala Leu Ala Leu Glu Ala Thr Arg Leu Val Pro Gly Ser Gly  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Val Arg Ala Val Ala Thr Arg Gly Leu Pro Gly Ala Ala Thr Gly Val  
               
               
                             340                 345                 350  
               
               
                   
               
               
                 Ser Leu Asp Gly Gly Ala Val Leu Gly Leu Gly Ala Arg Thr Ala Ala  
               
               
                         355                 360                 365  
               
               
                   
               
               
                 Ser Ala Pro Leu Val Leu Ala Thr Arg Thr Gly Lys Val Leu Lys Arg  
               
               
                     370                 375                 380  
               
               
                   
               
               
                 Ser Ala Ala Pro Ser Ala Arg Arg Pro Asp Thr Val Leu Pro Val Pro  
               
               
                 385                 390                 395                 400  
               
               
                   
               
               
                 Pro Pro Gly Ala Phe Gly Gly Ala Ala Gly Gly Leu Thr Pro Ser Ser  
               
               
                                 405                 410                 415  
               
               
                   
               
               
                 Ala Gly Val Arg Gly Thr Val Ser Pro Leu Thr Ala Thr Pro Lys Cys  
               
               
                             420                 425                 430  
               
               
                   
               
               
                 Ala Val Gly Arg Asn Glu Glu Asn Arg Gln Val Met Gln Pro Gly Thr  
               
               
                         435                 440                 445  
               
               
                   
               
               
                 Ala Gln Val Ser Trp Ala Val Gln Met Ala Glu Gln Gly Leu Leu Thr  
               
               
                     450                 455                 460  
               
               
                   
               
               
                 Gly Ser Ala Tyr Gln Arg Pro Ala Asn Phe Ala Asn Leu Gly Leu Val  
               
               
                 465                 470                 475                 480  
               
               
                   
               
               
                 Ala Tyr Ser Pro Asn Gly Asp Phe Gly Lys Val Ala Leu His His Pro  
               
               
                                 485                 490                 495  
               
               
                   
               
               
                 Ser Gly Asp Ser Trp Asp Ser Val Pro Arg Ser Val Tyr Gln Ala Ile  
               
               
                             500                 505                 510  
               
               
                   
               
               
                 Val Ala Gln Glu Ser Asn Tyr Ser Gln Ala Ser Trp His Ser Leu Pro  
               
               
                         515                 520                 525  
               
               
                   
               
               
                 Gly Ile Pro Gly Asn Pro Leu Ile Ala Asp Tyr Tyr Gly Ala Gly Gly  
               
               
                     530                 535                 540  
               
               
                   
               
               
                 Ser  
               
               
                 545  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 32  
               
               
                 &lt;211&gt; LENGTH: 30  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Description of Artificial Sequence: degenerated  
               
               
                       oligonucleotide primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 32  
               
               
                   
               
               
                 atcgtctaga csgasacstc saacgagtts                                      30  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 33  
               
               
                 &lt;211&gt; LENGTH: 28  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Description of Artificial Sequence: degenerated  
               
               
                       oligonucleotide primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 33  
               
               
                   
               
               
                 atcgaagctt sgasccctcg tggacgcc                                        28