Patent Publication Number: US-2020291411-A1

Title: Inducible Production-Phase Promoters for Coordinated Heterologous Expression in Yeast

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This current application is a continuation of U.S. patent application Ser. No. 15/469,452, filed Mar. 24, 2017, entitled “Inducible Production-Phase Promoters for Coordinated Heterologous Expression in Yeast” to Harvey et al., which claims priority under 35 U.S.C. 119(e) to U.S. Provisional Application Ser. No. 62/313,108, filed Mar. 24, 2016, the disclosures of which are each incorporated herein by reference in its entirety. 
    
    
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 
     This invention was made with Government support under contract GM110706 awarded by the National Institutes of Health. The Government has certain rights in the invention. 
    
    
     REFERENCE TO A SEQUENCE LISTING SUBMITTED ELECTRONICALLY VIA EFS-WEB 
     The instant application contains a Sequence Listing which has been filed electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Jun. 3, 2020, is named “05041CONseqlist_ST25.txt” and is 104 bytes in size. 
     FIELD OF THE INVENTION 
     The invention is generally directed to systems and constructs for heterologous expression in yeast, and more specifically to a set of inducible promoters that can be combined for coordinated expression of multiple genes and methods related to their construction and use. 
     BACKGROUND 
       Saccharomyces  ( S. ) is a genus of fungi composed of different yeast species. The genus can be divided into two further subgenera  S. sensu stricto  and  S. sensu lato.  The former have relatively similar characteristics, including the ability to interbreed, exhibiting uniform karyotype of sixteen chromosomes, and their use in the fermentation industry. The later are more diverse and heterogeneous. Of particular importance is the  S. cerevisiae  species within the  S. sensu stricto  subgenus, which is a popular model organism used for genetic research. 
     The yeast  S. cerevisiae  is a powerful host for the heterologous expression of biosynthetic systems, including production of biofuels, commodity chemicals, and small molecule drugs. The yeast&#39;s genetic tractability, ease of culture at both small and large scale, and a suite of well-characterized genetic tools make it a desirable system for heterologous expression. Occasionally, production systems require coordinated expression of two or more heterologous genes. Coordinated expression systems in bacteria (e.g.,  E. coli ) has long exploited the operon structure of bacterial gene clusters (e.g., lac operon), allowing a single promoter to control the expression of multiple genes. The construction of synthetic operons therefore allows a single inducible promoter to control the timing and strength of expression of an entire synthetic system. In yeast, many heterologous-expression systems do not rely on the operon system, but instead rely on a one-promoter, one-gene paradigm. Accordingly, multi-gene heterologous expression in most yeast strains is performed using multiple expression cassettes with a well-characterized promoter and terminator, each on a single expression vector (e.g., plasmid DNA) (See D. Mumberg, R. Muller, and M. Funk  Gene  156:119-22, 1995, which is incorporated herein by reference). With traditional restriction-ligation cloning, it is also possible to recycle a promoter on a single plasmid by the serial cloning of multiple genes (M. C. Tang, et al.,  J Am Chem Soc  137:13724-27, 1995). 
     SUMMARY OF THE INVENTION 
     Many embodiments of the invention are directed to a DNA molecule composition comprising at least one exogenous DNA vector comprising at least two different production-phase promoters; wherein the two production-phase promoters are each capable of repressing heterologous expression of an exogenous gene in a  Saccharomyces cerevisiae  cell when the  S. cerevisiae  cell predominantly exhibits anaerobic energy metabolism; and wherein the two production-phase promoters are each also capable of inducing heterologous expression of the exogenous gene in the  S. cerevisiae  cell when the  S. cerevisiae  cell predominantly exhibits aerobic energy metabolism. 
     In further embodiments the at least one exogenous DNA vector further comprising a heterologous gene; wherein the heterologous gene Sequence is derived from a species other than  S. cerevisiae;  and wherein the heterologous gene is situated proximately downstream of one of the two production promoters such that the heterologous gene expression can be repressed and induced by the production promoter that is proximately upstream from the heterologous gene. 
     In more embodiments, the anaerobic energy metabolism is defined by the catabolism of a fermentable carbon source. 
     In further more embodiments, the fermentable carbon source is glucose or dextrose. 
     In even further more embodiments, the aerobic energy metabolism is defined by the catabolism of a nonfermentable carbon source. 
     In even further more embodiments, the nonfermentable carbon source is ethanol or glycerol. 
     In even further more embodiments, the DNA molecule compositions further comprise a  S. cerevisiae  cell, wherein the exogenous DNA vector exists within the  S. cerevisiae cell.    
     In even further more embodiments, at least one of the at least two production phase promoters comprises a sequence of an endogenous production-phase promoter of  S. cerevisiae.    
     In even further more embodiments, the production-phase promoter is substantially similar to a sequence selected from the group consisting of the  S. cerevisiae  ADH2 promoter (Seq. ID No. 1),  S. cerevisiae  PCK1 promoter (Seq. ID No. 2), the  S. cerevisiae  MLS1 promoter (Seq. ID No. 3), the  S. cerevisiae  ICU promoter (Seq. ID No. 4), the  S. cerevisiae  YLR307C-A promoter (Seq. ID No. 5), the  S. cerevisiae  YGRO67C promoter (Seq. ID No. 6), the  S. cerevisiae  IDP2 promoter (Seq. ID No. 7), the  S. cerevisiae  ADY2 promoter (Seq. ID No. 8), the  S. cerevisiae  GAC1 promoter (Seq. ID No. 9), the  S. cerevisiae  ECM13 promoter (Seq. ID No. 10), the  S. cerevisiae  FAT3 promoter (Seq. ID No. 11), the  S. cerevisiae  PUT1 promoter (Seq. ID No. 12), the  S. cerevisiae  NQM1 promoter (Seq. ID No. 13), the  S. cerevisiae  SFC1 promoter (Seq. ID No. 14), the  S. cerevisiae  JEN1 promoter (Seq. ID No. 15), the  S. cerevisiae  SIP18 promoter (Seq. ID No. 16), the  S. cerevisiae  ATO2 promoter (Seq. ID No. 17), the  S. cerevisiae  YIG1 promoter (Seq. ID No. 18), and the  S. cerevisiae  FBP1 promoter (Seq. ID No. 19). 
     In even further more embodiments, at least one of the at least two production phase promoters comprises a Sequence of an exogenous production-phase promoter of  S. cerevisiae.    
     In even further more embodiments, the production-phase promoter is substantially similar to a sequence selected from the group consisting of the  S. paradoxus  ADH2 promoter (Seq. ID No. 36), the  S. kudriavzevii  ADH2 promoter (Seq. ID No. 37),  S. bayanus  ADH2 promoter (Seq. ID No.38),  S. paradoxus  PCK1 promoter (Seq. ID No. 41), the  S. kudriavzevii  PCK1 promoter (Seq. ID No. 42),  S. bayanus  PCK1 promoter (Seq. ID No. 43),  S. paradoxus  MLS1 promoter (Seq. ID No. 44), the  S. kudriavzevii  MLS1 promoter (Seq. ID No. 45),  S. bayanus  MLS1 promoter (Seq. ID No. 46),  S. paradoxus  ICL1 promoter (Seq. ID No. 47), the  S. kudriavzevii  ICL1 promoter (Seq. ID No. 48), and  S. bayanus  ICL1 promoter (Seq. ID No. 49). 
     Many embodiments are directed to at least one exogenous DNA vector comprising a production-phase promoter, wherein the production-phase promoter is substantially similar to a sequence selected from the group consisting of the  S. cerevisiae  PCK1 promoter (Seq. ID No. 2), the  S. cerevisiae  MLS1 promoter (Seq. ID No. 3), the  S. cerevisiae  ICL1 promoter (Seq. ID No. 4), the  S. cerevisiae  YLR3O7C-A promoter (Seq. ID No. 5), the  S. cerevisiae  YGRO67C promoter (Seq. ID No. 6), the  S. cerevisiae  IDP2 promoter (Seq. ID No. 7), the  S. cerevisiae  ADY2 promoter (Seq. ID No. 8), the  S. cerevisiae  GAC1 promoter (Seq. ID No. 9), the  S. cerevisiae  ECM13 promoter (Seq. ID No. 10), the  S. cerevisiae  FAT3 promoter (Seq. ID No. 11), the  S. cerevisiae  PUT1 promoter (Seq. ID No. 12), the  S. cerevisiae  NQM1 promoter (Seq. ID No. 13), the  S. cerevisiae  SFC1 promoter (Seq. ID No. 14), the  S. cerevisiae  JEN1 promoter (Seq. ID No. 15), the  S. cerevisiae  SIP18 promoter (Seq. ID No. 16), the  S. cerevisiae  ATO2 promoter (Seq. ID No. 17), the  S. cerevisiae  YIG1 promoter (Seq. ID No. 18), the  S. cerevisiae  FBP1 promoter (Seq. ID No. 19), the  S. paradoxus  ADH2 promoter (Seq. ID No. 36), the  S. kudriavzevii  ADH2 promoter (Seq. ID No. 37),  S. bayanus  ADH2 promoter (Seq. ID No.38),  S. paradoxus  PCK1 promoter (Seq. ID No. 41), the  S. kudriavzevii  PCK1 promoter (Seq. ID No. 42),  S. bayanus  PCK1 promoter (Seq. ID No. 43),  S. paradoxus  MLS1 promoter (Seq. ID No. 44), the  S. kudriavzevii  MLS1 promoter (Seq. ID No. 45),  S. bayanus  MLS1 promoter (Seq. ID No. 46),  S. paradoxus  ICL1 promoter (Seq. ID No. 47), the  S. kudriavzevii  ICL1 promoter (Seq. ID No. 48), and  S. bayanus  ICL1 promoter (Seq. ID No. 49). 
     In further embodiments, the selected production-phase promoter is substantially similar to the  S. cerevisiae  PCK1 promoter sequence (Seq. ID No. 2). 
     In more embodiments, the selected production-phase promoter is substantially similar to the  S. cerevisiae  MLS1 promoter sequence (Seq. ID No. 3). 
     In further more embodiments, the selected production-phase promoter is substantially similar to the  S. cerevisiae  ICL1 promoter sequence (Seq. ID No. 4). 
     In even further more embodiments, the selected production-phase promoter is substantially similar to a sequence selected from the group consisting of the  S. paradoxus  ADH2 promoter (Seq. ID No. 36), the  S. kudriavzevii  ADH2 promoter (Seq. ID No. 37), and  S. bayanus  ADH2 promoter (Seq. ID No. 38). 
     In even further more embodiments, the selected the production-phase promoter is substantially similar to a sequence selected from the group consisting of  S. paradoxus  PCK1 promoter (Seq. ID No. 41), the  S. kudriavzevii  PCK1 promoter (Seq. ID No. 42),  S. bayanus  PCK1 promoter (Seq. ID No. 43),  S. paradoxus  MLS1 promoter (Seq. ID No. 44), the  S. kudriavzevii  MLS1 promoter (Seq. ID No. 45),  S. bayanus  MLS1 promoter (Seq. ID No. 46),  S. paradoxus  ICL1 promoter (Seq. ID No. 47), the  S. kudriavzevii  ICL1 promoter (Seq. ID No. 48), and  S. bayanus  ICL1 promoter (Seq. ID No. 49). 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. 
       The description will be more fully understood with reference to the following figures and data graphs, which are presented as exemplary embodiments of the invention and should not be construed as a complete recitation of the scope of the invention. 
         FIG. 1A  illustrates a yeast phase chart displaying yeast cell concentration in relation to time to provide reference for various embodiments of the invention. 
         FIG. 1B  illustrates a yeast phase chart displaying glucose concentration in relation to time to provide reference for various embodiments of the invention. 
         FIG. 1C  illustrates a yeast phase chart displaying ethanol or glycerol concentration in relation to time to provide reference for various embodiments of the invention. 
         FIG. 2A  illustrates a DNA vector having a production-phase promoter in accordance with an embodiment of the invention. 
         FIG. 2B  illustrates a DNA vector having multiple production-phase promoters in accordance with an embodiment of the invention. 
         FIG. 3A  illustrates a DNA expression vector having a production-phase promoter within an expression cassette in accordance with an embodiment of the invention. 
         FIG. 3B  illustrates a DNA expression vector having multiple production-phase promoters, each within an expression cassette in accordance with an embodiment of the invention. 
         FIG. 4  illustrates a method to construct and utilize production-phase promoter DNA vectors in accordance with various embodiments of the invention. 
         FIG. 5  is a heat map graphic generated in accordance with various embodiments of the invention with data of expression of enhanced-Green Fluorescent Protein driven by various  S. cerevisiae  promoters. 
         FIG. 6  is a data graph of enhanced-Green Fluorescent Protein expression driven by various  S. cerevisiae  promoters, generated in accordance with various embodiments of the invention, 
         FIG. 7  illustrates fluorescence intensity of enhanced-Green Fluorescent Protein driven by various promoters, generated in accordance with various embodiments of the invention. 
         FIG. 8  illustrates a phylogenetic tree of  Saccharomyces sensu stricto  subgenus to provide reference for various embodiments of the invention. 
         FIG. 9  illustrates a multiple sequence alignment of various  Saccharomyces sensu stricto  species&#39; upstream activating sequences in ADH2 promoters to provide reference for various embodiments of the invention. 
         FIG. 10  illustrates homology between various  Saccharomyces sensu stricto  species&#39; ADH2 promoters to provide reference for various embodiments of the invention. 
         FIG. 11  is a heat map graphic generated in accordance with various embodiments of the invention with data of expression of enhanced-Green Fluorescent Protein driven by various  S. sensu stricto  ADH2 promoters. 
         FIG. 12  is a data graph of enhanced-Green Fluorescent Protein expression driven by various  S. sensu stricto  ADH2 promoters, generated in accordance with various embodiments of the invention. 
         FIG. 13  illustrates four multi-gene expression vector constructs, each to generate a product compound, in accordance with an embodiment of the invention, 
         FIG. 14  illustrates a biosynthetic process that produces the compound emindole SB via a fungal four-gene cluster to provide reference for various embodiments of the invention. 
         FIG. 15  is a data graph of the production results of two product compounds generated in accordance of an embodiment of the invention, 
         FIG. 16  illustrates two plasmid vector constructs in accordance with an embodiment of the invention. 
     
    
    
     BRIEF DESCRIPTION OF THE SEQUENCE LISTING 
     The current disclosure incorporates a sequence listing in accordance with the WIPO Standard ST,25. The Sequence listing embodies sixty-six nucleic acid sequences (Seq ID Nos, 1-66), which are referenced in Table 3 and throughout the specification. 
     DETAILED DESCRIPTION 
     Turning now to the drawings and data, embodiments of the invention are generally directed to systems and constructs of heterologous expression during the production phase of yeast. In many of these embodiments, the expression system involves coordinated expression of multiple heterologous genes. More embodiments are directed to production-phase promoter systems having promoters that are inducible upon an event in the yeast&#39;s growth or by the nutrients and supplements provided to the yeast. Specifically, a number of embodiments are directed to the promoters that are capable of being repressed in the presence of glucose and/or dextrose. In more embodiments, the promoters are capable of being induced in the presence of glycerol and/or ethanol. In additional embodiments, at least one production-phase promoter exists within an exogenous DNA vector, such as (but not limited to), for example, a shuttle vector, cloning vector, and/or expression vector. Embodiments are also directed to the use of expression vectors for the expression of heterologous genes in a yeast expression system. 
     Controlled gene expression is desirable in heterologous expression systems. For example, it would be desirable to express heterologous genes for production during a longer stable phase. Accordingly, decoupling the anaerobic growth and aerobic production phases of a culture allows the yeast to grow to high density prior to introducing the metabolic stress of expressing unnaturally high amounts of heterologous protein. In accordance with many embodiments, the anaerobic growth phase is defined by the yeast culture&#39;s energy metabolism in which the yeast cells predominantly catabolize fermentable carbon sources (e.g., glucose and/or dextrose), and a high growth rate (i.e., short doubling-time). In contrast, and in accordance with several embodiments, the aerobic production phase is defined by the yeast culture&#39;s energy metabolism in which the yeast cells predominantly catabolize nonfermentable carbon sources (e.g., ethanol and/or glycerol), and a steady growth rate (i.e., long doubling-time). Accordingly, each yeast cell&#39;s energy metabolism is binary and dependent on the local concentration of the carbon source. 
       FIG. 1A  depicts the phases of a yeast culture when provided a fermentable sugar, such as glucose or dextrose sugar, at a concentration of around 2-4% as its main carbon source. Initially, a yeast culture will predominantly catabolize the fermentable sugar, which correlates with an exponential growth with very high doubling rates. The growth phase typically lasts approximately 4-10 hours. During this phase, the catabolism of the fermentable sources results in the production of ethanol and glycerol. 
     Once glucose becomes scarce, the growth of a yeast culture passes a diauxic shift and begins to predominantly catabolize nonfermentable carbon sources (e.g., ethanol and/or glycerol) ( FIG. 1B ). The predominant catabolism of nonfermentable carbon source correlates with a longer and more stable production phase that can last for several days, or even weeks in an industrial-like setting ( FIG. 1A ). During the production phase, yeast cultures reach and maintain a high concentration, but have a much lower doubling time ( FIG. 1A ). Due to the decrease in doubling rate, yeast cultures no longer expend a great amount of energy and resources on rapid growth and thus can reallocate that energy and those resources to other biological activities, including heterologous expression. Accordingly, it is hypothesized that limiting the transcription of heterologous genes to the production phase would allow a yeast culture to reach a high, healthy confluency that would in turn allow better heterologous protein expression and biosynthetic production. 
     In yeast, transcriptional regulation can be achieved in several ways, including inducement by chemical substrates (e.g., copper or methionine), the tetON/OFF system, and promoters engineered to bind unnatural hybrid transcription factors. Perhaps the most commonly employed inducible promoters are the promoters controlled by the endogenous GAL4 transcription factor. GAL4 promoters are strongly repressed in glucose, and upon switching to galactose as a carbon source, strong induction of transcription is observed (M. Johnston and R. W. Davis,  Mol. Cell Biol.  4:1440-48, 1984, the disclosure of which is incorporated herein by reference). While this system leads to high-level transcription, only four galactose-responsive promoters are known, and galactose is both a more expensive and a less efficient carbon source as compared to glucose ( S. Ostergaard,  et al.,  Biotechnol. Bioeng.  68:252-59, 2000, the disclosure of which is incorporated herein by reference). 
     Other carbon-source dependent promoters have also been used for heterologous gene expression. The  S. cerevisiae  ADH2 gene exhibits significant derepression upon depletion of glucose as well as strong induction by either glycerol or ethanol (K. M. Lee &amp; N. A. DeSilva Yeast. 22:431-40, 2005, the disclosure of which is incorporated herein by reference). Once induced, genes driven by the ADH2 promoter (pADH2) display expression levels equivalent to those driven by highly expressed constitutive counterparts. This induction profile was found to work in heterologous expression studies, as the system auto-induces upon glucose depletion in the late stages of fermentative growth after cells have undergone diauxic shift. The ADH2 promoter has been used extensively for yeast heterologous expression studies, resulting in high-level expression of several heterologous biosynthetic proteins (For example, see C. D. Reeves, et al., Appl. Environ. Microbiol. 74:5121-29, 2008, the disclosure of which is incorporated herein by reference). 
     As shown in  FIG. 1C , the concentration of ethanol and glycerol increases as glucose and dextrose sugar decreases, due to anaerobic glycolysis (i.e., breaking down the fermentable sugar) and subsequent fermentation (i.e., converting the broken-down glucose into alcohol) and glycerol biosynthesis (i.e., converting the broken-down glucose into glycerol). Upon fermentable sugar depletion, yeast cultures undergo a diauxic shift and begin to use ethanol and glycerol as a carbon source instead of glucose. A diauxic shift, as understood in the art, is defined as a point in time when an organism switches consumption of one source for energy, to another source. This shift requires significant changes to a yeast culture&#39;s gene-expression pattern. Accordingly, it is hypothesized that higher concentrations of ethanol, (i.e., ˜2-4%) and or glycerol ˜2%) could be used to stimulate promoters that either directly or indirectly respond to these concentrations (See  FIGS. 1A and 1C ). 
     Various embodiments of the invention are based on the discovery of inducible promoters that can be used for the coordinated expression of multiple genes (e.g., gene cluster pathway) in  Saccharomyces  yeast. Described below are sets of inducible promoters from  S. cerevisiae  and related species that are inactive during anaerobic growth, activating transcription only after a diauxic shift when glucose is near-depleted and the yeast cells are respiring (i.e., the production phase). As portrayed in various embodiments, various production-phase promoters are auto-inducing and allow automatic decoupling of the growth and production phases of a culture and thus initiate heterologous expression without the need for exogenous inducers. It should be noted, however, that many embodiments of the invention include production-phase promoters that are also inducible in the presence of nonfermentable carbon-sources (e.g., ethanol and/or glycerol) supplied to the yeast. As such, multiple embodiments employ recombinant production-phase promoters that act much like constitutive promoters when the host yeast cultures are constantly maintained in ethanol- and/or glycerol-containing media. 
     Once activated, the strength of various production-phase promoters can vary as much as 50-fold in accordance with numerous embodiments of the invention. The strongest production-phase promoters stimulate heterologous expression greater than that observed from strong constitutive promoters. The production-phase promoters could be employed in many different applications in which high expression of multiple genes is beneficial. Accordingly, the promoters can be used, for example, in multiple subunit protein production or for the production of biosynthetic compounds that are produced by multiple proteins within a pathway. Discussed in an exemplary embodiment below, embodiments of the invention are used to express multiple proteins involved in production of indole diterpene compound product. When compared to constitutive promoters, the production-phase promoters produced greater than a 2-fold increase in titer of the exemplary diterpene natural products. In other exemplary embodiments, it was found that the production-phase promoter system outperformed constitutive promoters by over 80-fold. Thus, these promoters can enable heterologous expression of biosynthetic systems in yeast. 
     The practice of several embodiments of the present invention will employ, unless otherwise indicated, conventional methods of chemistry, biochemistry, and molecular biology and recombinant DNA techniques within the skill of the art. Such techniques are explained fully in the literature. See, e.g., A. L. Lehninger, Biochemistry (Worth Publishers, Inc., 30 current addition); Sambrook, et al., Molecular Cloning: A Laboratory Manual (3 rd  Edition, 2001); Methods In Enzymology (S. Colowick and N. Kaplan eds., Academic Press, Inc.). 
     Inducible Production-Phase Promoters for Heterologous Expression in Yeast 
     In accordance with several embodiments of the invention, inducible production-phase promoters can be constructed into exogenous expression vectors for production of at least one protein in  Saccharomyces  yeast. In many embodiments, the constructed expression vectors have multiple inducible production-phase promoters in order to express multiple heterologous genes. 
     Several embodiments are directed to production-phase promoters and DNA vectors incorporating these promoters. Promoters, in general, are defined as a noncoding portion of DNA sequence situated proximately upstream of a gene to regulate and promote its expression. Typically, in  S. cerevisiae  and similar species, the promoter of a gene can be found within 500-bp upstream of a gene&#39;s translation start codon. 
     In accordance with several embodiments, production-phase promoters have two defining characteristics. First, production-phase promoters are capable of repressing heterologous expression of a gene in  S. cerevisiae  and similar species when the yeast is exhibiting anaerobic energy metabolism. As described previously, yeast exhibit anaerobic metabolism in the presence of a nontrivial concentration of fermentable carbon sources such as, for example, glucose or dextrose. In addition, production-phase promoters are also capable of inducing heterologous expression of a gene in  S. cerevisiae  and similar species when the yeast is exhibiting aerobic energy metabolism. As described previously, yeast exhibit aerobic metabolism when fermentable carbon sources are near depleted and the yeast cells switch to a catabolism of nonfermentable carbon sources such as glycerol or ethanol. These characteristics correspond to the phase charts in  FIGS. 1A-1C . Tables 1 and 2 provide several examples of production-phase promoters in accordance with several embodiments. Table 3 provides sequences that correspond with the promoters and the incorporated sequence listing. 
     The production-phase promoters can be characterized based on their level of transgene expression relative to each other and to constitutive promoters. As described in an exemplary embodiment below, it was found that the sequence of endogenous promoters of the  S. cerevisiae  genes ADH2, PCK1, MLS1, and ICL1 exhibited high-level expression and thus can be characterized as strong production-phase promoters (Table 1). Sequences of the endogenous promoters of the  S. cerevisiae  genes YLR307C-A, ORF-YGRO67C IDP2, ADY2, CACI, ECM13, and FATS exhibited mid-level expression and thus can be characterized as semi-strong production phase promoters (Table 1). In addition, sequences of the endogenous promoters of the  S. cerevisiae  genes PUT1, NQM1, SFC1, JEN1, SIP18, ATO2, YIG1, and FBP1 exhibited low-level expression and thus can be characterized as weak production-phase promoters (Table 1). 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 Production-Phase Promoters Expression Phenotype 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Gene 
                 Systematic 
                 Expression 
                 Sequence 
               
               
                   
                 Name 
                 Name 
                 Phenotype 
                 ID Number 
               
               
                   
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 ADH2 
                 YMR303C 
                 Strong 
                 1 
               
               
                   
                 PCK1 
                 YKR097W 
                 Strong 
                 2 
               
               
                   
                 MLS1 
                 YNL117W 
                 Strong 
                 3 
               
               
                   
                 ICL1 
                 YER065C 
                 Strong 
                 4 
               
               
                   
                 YLR307C-A 
                 YLR307C-A 
                 Semi-Strong 
                 5 
               
               
                   
                 YGR067C 
                 YGR067C 
                 Semi-Strong 
                 6 
               
               
                   
                 IDP2 
                 YLR174W 
                 Semi-Strong 
                 7 
               
               
                   
                 ADY2 
                 YCR010C 
                 Semi-Strong 
                 8 
               
               
                   
                 GAC1 
                 YOR178C 
                 Semi-Strong 
                 9 
               
               
                   
                 ECM13 
                 YBL043W 
                 Semi-Strong 
                 10 
               
               
                   
                 FAT3 
                 YKL187C 
                 Semi-Strong 
                 11 
               
               
                   
                 PUT1 
                 YLR142W 
                 Weak 
                 12 
               
               
                   
                 NQM1 
                 YGR043C 
                 Weak 
                 13 
               
               
                   
                 SFC1 
                 YJR095W 
                 Weak 
                 14 
               
               
                   
                 JEN1 
                 YKL217W 
                 Weak 
                 15 
               
               
                   
                 SIP18 
                 YMR175W 
                 Weak 
                 16 
               
               
                   
                 ATO2 
                 YNR002C 
                 Weak 
                 17 
               
               
                   
                 YIG1 
                 YPL201C 
                 Weak 
                 18 
               
               
                   
                 FBP1 
                 YLR377C 
                 Weak 
                 19 
               
               
                   
                   
               
            
           
         
       
     
     The closely related  S. sensu stricto  species have similar genetics and growth characteristics. Accordingly, the phase charts provided in  FIGS. 1A-1C  apply generally to  S. sensu stricto  species. Table 2 provides a list of strong production-phase exogenous promoters of similarly related species in accordance with numerous embodiments of the invention. 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 Strong Production-Phase Promoters of  S. sensu stricto  species 
               
            
           
           
               
               
               
               
            
               
                   
                   
                 Gene 
                 Sequence 
               
               
                   
                 Species 
                 Name 
                 ID Number 
               
               
                   
                   
               
               
                   
                 
                   S. paradoxus 
                 
                 ADH2 
                 36 
               
               
                   
                 
                   S. kudriavzevii 
                 
                 ADH2 
                 37 
               
               
                   
                 
                   S. bayanus 
                 
                 ADH2 
                 38 
               
               
                   
                 
                   S. paradoxus 
                 
                 PCK1 
                 41 
               
               
                   
                 
                   S. kudriavzevii 
                 
                 PCK1 
                 42 
               
               
                   
                 
                   S. bayanus 
                 
                 PCK1 
                 43 
               
               
                   
                 
                   S. paradoxus 
                 
                 MLS1 
                 44 
               
               
                   
                 
                   S. kudriavzevii 
                 
                 MLS1 
                 45 
               
               
                   
                 
                   S. bayanus 
                 
                 MLS1 
                 46 
               
               
                   
                 
                   S. paradoxus 
                 
                 ICL1 
                 47 
               
               
                   
                 
                   S. kudriavzevii 
                 
                 ICL1 
                 48 
               
               
                   
                 
                   S. bayanus 
                 
                 ICL1 
                 49 
               
               
                   
                   
               
            
           
         
       
     
     It should be noted that substantially similar sequences to the production-promoter sequences are expected to regulate heterologous expression in  S. cerevisiae  and achieve similar results. Accordingly, a substantially similar sequence of a production-phase promoter, in accordance with numerous embodiments, is any sequence with a high homology such that when regulating heterologous expression in  S. cerevisiae  that it achieves substantially similar results. For example, in an exemplary embodiment below, it was found that the ADH2 promoter of  S. bayanus  is only 61% homologous, yet achieved strong heterologous expression in  S. cerevisiae,  similar to the endogenous ADH2 promoter. 
     In  FIG. 2A , an exemplary schematic of a section of an exogenous DNA vector (e.g., cloning vector, expression vector, and/or shuttle vector) having a production-phase promoter sequence embedded within. A vector is capable of transferring nucleic acid sequences to target cells (e.g., yeast). Typical DNA vectors include, but are not limited to, plasmid or viral constructs. DNA vectors are also meant to include a kit of various linear DNA fragments that are to be recombined to form a plasmid or other functional construct, as is common in yeast homologous recombination methods (See e,g., Z. Shao, H. Zhao &amp; H. Zhao, 2009,  Nucleic Acids Research  37:e16, 2009, the disclosure of which is incorporated herein by reference). Often, embodiments of cloning vectors will incorporate other sequences in addition to the production-phase promoter. As depicted in  FIG. 2A , the exemplary cloning vector has a terminator sequence and cloning/recombination sequence in addition to the production-phase promoter, each of which can assist with expression vector construction. Furthermore, other sequences necessary for growth and amplification can be incorporated into the promoter vector. Embodiments of these sequences may include, for example, at least one appropriate origin of replication, at least one selectable marker, and/or at least one auxotrophic marker. It should be noted, however, that various embodiments of the invention are not required to contain cloning, terminator, or either sequences. For example, embodiments of a typical shuttle vector may only contain the production-phase promoter sequence along with the necessary sequences for amplification in a biological system. 
     For purposes of this application, an exogenous DNA vector is any DNA vector that was constructed, at least in part, exogenously. Accordingly, DNA vectors that are assembled using the yeast&#39;s own cell machinery (e.g., yeast homologous recombination) would still be considered exogenous if any of the DNA molecules transduced within yeast for recombination contain exogenous sequence or were produced by a non-host methodology, such as, for example, chemical synthesis, PCR amplification, or bacterial amplification. 
     As shown in  FIG. 2B , various embodiments of the invention are directed to DNA vectors having multiple production-phase promoters. In these various embodiments, multiple different production-phase promoters are incorporated, preferably each having a unique sequence and derived from a different gene and/or  S. sensu stricto  species. Having unique promoter sequences can prevent complications that can arise during product production in yeast, such as, for example, unwanted DNA recombination at sites similar to the promoter sequences that render the DNA vector constructs undesirable. In many embodiments, the DNA vector has at least two production-phase promoters and up to a number that still yields the vector useful. As the size of the DNA vector increases, the utility may decrease, as larger vectors may become unwieldly for the intended organism to handle. For example, plasmids for amplification in  E. coli  are often somewhere between 2,000 and 10,000 base pairs (bp) but can handle up to 20,000 bp or so. Likewise, plasmids for amplification and growth in yeast can vary from approximately 10,000 to 30,000 bp. Viral vectors, on the other hand, often have a limited construct size and thus may require a more precise vector size. Thus, depending on vector and intended use, the number of production-phase promoters within a DNA vector will vary. 
     Although  FIG. 2B  depicts recombination sites, cloning sites, and terminator sequences, it should be noted that these sequences may or may not be included in various embodiments of DNA vectors having multiple production-phase promoters. The incorporation of these sequences or other various sequence is often dependent on the purpose of the DNA vector. For example, cloning vectors may not include a terminator sequence if that sequence is to be incorporated into an expression construct at another stage of assembly. 
       FIG. 3A  depicts an exemplary heterologous expression vector having a production-phase promoter for expression in yeast, in accordance with various embodiments of the invention. Expression constructs contain an expression cassette that minimally has a promoter, a heterologous gene, and a terminator sequence in order to produce an RNA molecule in an appropriate host. Expression cassette in accordance with numerous embodiments will have a production-phase promoter situated proximately upstream of a heterologous gene of which the promoter is to regulate expression. It should be understood, that the precise location of the production-phase promoter upstream of the heterologous gene may vary, but the promoter must be within a certain proximity to adequately function. 
     In many embodiments of the invention, a heterologous gene is any gene driven by a production-phase promoter, wherein the heterologous gene is different than the endogenous gene that the promoter regulates within its endogenous genome. Accordingly, a  S. cerevisiae  production-phase promoter could regulate another  S. cerevisiae  gene provided that the gene to be regulated is not the gene endogenously regulated. For example, the  S. cerevisiae  ADH2 promoter should not regulate the  S. cerevisiae  ADH2 gene; however, the  S. cerevisiae  ADH2 promoter can regulate any other  S. cerevisiae  gene or the ADH2 gene from any other species. Often, in accordance with many embodiments, the heterologous gene is from a different species than the species from which the production-promoter sequence was obtained. 
     Although not depicted, various embodiments of expression cassettes may include other sequences, such as, for example, intron sequences, Kozak-like sequences, and/or protein tag sequences (e.g., 6x-His) that may or may not improve expression, production, and/or purification. In yeast, various embodiments of expression vectors will also minimally have a yeast origin of replication (e.g., 2-micron) and an auxotrophic marker (e.g., URA3) in addition to the expression cassette. Other nonessential sequences may also be included, such as, for example, bacterial origins of replication and/or bacterial selection markers that would render the expression capable of amplification in a bacterial host in addition to a yeast host. Accordingly, various embodiments of expression vectors would include the essential sequences for heterologous expression in yeast and other various embodiments would include additional nonessential sequences. 
     In accordance with various embodiments, a DNA vector having a production-phase promoter expression cassette can be transformed into a yeast cell. Or alternatively, and in accordance with numerous embodiments, a DNA vector having a production-phase promoter expression cassette can be assembled within yeast using homologous recombination techniques. Once existing within a yeast cell, the production-phase promoter can regulate the expression of a heterologous gene in accordance with the yeast cell&#39;s energy metabolism. As described previously, and in accordance with many embodiments, production-phase promoters repress heterologous expression when the yeast cell is in an anaerobic energy metabolic state. Alternatively, and in accordance with a number of embodiments, production-phase promoters induce heterologous expression when the yeast cell is in an aerobic energy metabolic state. 
     Depicted in  FIG. 3B  are alternative exemplary heterologous expression vectors having multiple production-phase promoters for expression of multiple genes in yeast in accordance with numerous embodiments. In these embodiments, the expression vectors will include at least two expression cassettes, each with a unique promoter, gene, and terminator sequence in order to prevent unwanted recombination. The number of expression cassettes will vary based on vector construct design and application. For heterologous expression in  S. cerevisiae,  it has been found that plasmid expression vectors of approximately 30,000 bp are still tolerated. Thus, vectors containing up to seven production-phase promoter expression cassettes can be incorporated into an expression vector and have been found to be able to maintain adequate gene expression and protein production. Larger vectors with more expression cassettes may be tolerated. 
     Although  FIG. 3B  depicts multiple expression cassettes sequentially in the same orientation 5′ to 3′, it should be understood that the combination of two or more expression cassettes is not limited to sequential linear organization in the same orientation. Expression cassettes in accordance with many embodiments exist within the expression vector in any orientation and in any sequential order. Furthermore, it should be understood that other sequence elements of an expression vector (e.g., auxotrophic marker) may be among and/or between the multiple expression cassettes. Optimal vector design is likely to depend on various factors, such as, for example, optimizing the location of the auxotrophic marker to enable the final expression vector to include each expression cassette to be incorporated. 
     DNA heterologous expression vectors are a class of DNA vectors, and thus the description of general DNA vectors above also applies to the expression vectors. Accordingly, many embodiments of the expression vectors are formulated into a plasmid vector, a viral vector, or a kit of linear DNA fragments to be recombined into a plasmid by yeast homologous recombination. In several of these embodiments, the end-product vector contains at least one expression cassette having a production-phase promoter. It should be understood, that in addition to the at least one production-phase promoter, some vector embodiments incorporate expression cassettes that include other promoters, such as (but not limited to), constitutive promoters that maintain high expression during the growth and production phases. 
     The various embodiments of heterologous expression vectors having at least one production-phase promoter can be used in numerous applications. For example, high expression in the production phase can lead to better, prolonged expression, as compared to constitutive promoters. In many applications, the end product is a protein from a single gene or a protein complex of multiple genes to be purified from the culture. For these applications, high, prolonged expression using production-phase promoters can lead to better yields of proteins. Furthermore, when the heterologous protein is toxic to the host yeast cells, the use of production-phase promoters prevents the expression of the toxic protein during growth phase, allowing the yeast to reach a healthy confluency before mass protein production. 
     The production-phase promoter vectors can also benefit the production of a biosynthetic compound from a gene cluster. Many products derived from various natural species are produced from a cluster of genes with sequential enzymatic activity. For example, the antibiotic emindole SB is produced from a cluster of four genes that is expressed in  Aspergillus tubingensis.  To reproduce this gene cluster in a yeast production model, a production-promoter vector system with four different expression cassettes could work. This system would allow the yeast to reach a healthy confluency before the energy-draining expression of four heterologous proteins begin, leading to better overall yields of the antibiotic product. In fact, experimental results provided in an exemplary embodiment described below demonstrate that a production-phase promoter vector outperformed a constitutive promoter vector approximately 2-fold to produce the emindole SB product. 
       FIG. 4  depicts an exemplary process (Process 400) to implement various embodiments of production-phase promoters. To begin, Process 400 identifies and selects at least one gene for heterologous expression in yeast (401). The choice of gene(s) for expression would depend on the desired outcome. For example, to produce a biosynthetic compound, one would likely select to express all the genes within a biosynthetic gene cluster of a particular organism. Once the gene(s) have been selected, Process 400 then appropriates DNA molecules having the coding sequence of the selected genes (403). As is well known in the art, there are many ways to appropriate DNA molecules, which include chemical synthesis, extraction directly from the biological source, or amplification of a gene by polymerase chain reaction (PCR). 
     Process 400 then uses the appropriated DNA molecules to assemble these molecules into an expression vector having production-phase promoters (405). There are many ways to assemble DNA expression vectors that are well known in the art, which include popular methodologies such as homologous recombination and restriction digestion with subsequent ligation. After assembly, the resultant expression vectors can be expressed in  Saccharomyces  yeast to obtain the desired outcome (407). 
     EXEMPLARY EMBODIMENTS 
     Biological data supports the systems and constructs of production-phase promoter DNA vectors and applications thereof. Provided below are several examples of incorporating production-phase promoters into DNA vectors. Many of these vectors were used to produce biosynthetic products from multi-gene clusters derived from various fungal species. Compared to a constitutive promoter system, a production-phase promoter system in accordance with various embodiments produced several fold greater product. 
     Production Phase Promoter Expression Analysis 
     Because the ADH2 promoter (Seq. ID No. 1) has properties of a production-phase promoter, a panel of promoter sequences was compared to the ADH2 promoter to identify other production-phase promoters. To begin, endogenous  S. cerevisiae  genes were identified that appeared co-regulated with ADH2 in a previous genome-wide transcription study (Z. Xu. et al., Nature 457:1033-37, 2009, the disclosure of which is incorporated herein by reference). In this study, transcription of yeast genes was quantified during mid-exponential growth in several types of growth media. Of the 5171 ORFs examined, 35 appeared co-regulated with ADH2, with co-regulation defined as a greater than two-fold increase in expression with a non-fermentable carbon source (ethanol in a yeast-peptone-ethanol (YPE) media) as compared to a fermentable carbon source (dextrose in a yeast-peptone-dextrose (YPD) media). Because these data were collected at a single time point and assessed transcription of genes in their native context, their ability to co-regulate heterologous genes in a production-phase promoter system required further validation and characterization. 
     A detailed characterization of the ability of 34 selected promoters to control expression of heterologous genes was performed. A promoter was defined as the shorter of (a) 500 bp upstream of the start codon, or (b) the entire 5′ intergenic region. Each promoter was cloned upstream of the gene for monomeric enhanced GFP (eGFP) and integrated each of the resulting cassettes in a single copy at the ho locus of individual strains. Control strains were included in which strong constitutive FBA1 and TDH3 promoters were cloned upstream of eGFP in an identical manner. The 35 promoter sequences can be found in Table 3. (Seq. ID Nos. 2-35). In order to compare the 35 putative production-phase promoters, the expression of eGFP protein was assessed over 72 hours in each strain by flow cytometry in media with both fermentable (YPD) and non-fermentable (YPE) carbon sources ( FIGS. 5 and 6 ). All cultures were started in YPD media and analysis of eGFP expression began when cells were in the midst of exponential fermentative growth (OD600=0.4, 0 hrs). At this point, cells were either left to continue growth in YPD or spun-down and resuspended in YPE. Consistent with previous work, pADH2 was entirely repressed during exponential fermentative growth (0 hrs) unlike the constitutive promoters pTDH3 and pFBA1, which were expressed at near maximum levels regardless of phase. Moderate expression from pADH2 was observed after a further 6 hours in YPD culture or following a growth media switch to YPE. Within 24hrs, expression reached levels exceeding those observed in the strong constitutive systems. Cytometry histograms and fluorescence microscopy demonstrated that within 48 hours, &gt;95% of all cells with pADH2 and pPCK1 driven expression were fluorescing above background ( FIG. 6 ). Protein expression levels spanned 50-15 fold, with most showing little or no expression until 24 hours into the culture ( FIGS. 5 and 6 ). Transgene expression driven by the PCK1, MLS1, and ICL1 promoters (Seq. ID Nos. 2-4) not only showed the same timing of expression as pADH2, but also expressed at an equivalently high level. The promoters of genes YLR307C-A, YGRO67C, IDP2, ADY2, GAC1, ECM13 and FAT3 (Seq. ID Nos. 5-11) displayed semi-strong transgene expression ( FIG. 5 ). In addition, the promoters of genes PUT1, NQM1, SFC1, JEN1, SIP18, ATO2, YIG1, and FBP1 (Seq. ID Nos. 12-19) displayed weak of transgene expression ( FIGS. 5 and 6 ). The promoter PHO89 (Seq. ID No. 20) did not exhibit strong repression in during the growth phase ( FIG. 5 , 0 and 6 hours). The results of the other sequences are also depicted in  FIG. 5  (Seq. ID Nos. 22-36). The constitutive promoters pTDH3 and pFBA1 (Seq. ID Nos. 50 and 52) were used as controls ( FIGS. 5 and 6 ). 
     The above analysis identified a large set of co-regulated promoters spanning a wide range of expression levels, three of which were as strong as pADH2. However, a more extensive set of strong production-phase promoters is desirable for assembly of constructs having multi-gene pathways, especially pathways having more than four genes. To identify other production-phase promoter candidates, the genomes of five closely related species within the  S. sensu stricto  complex were examined ( FIG. 8 ). The promoter region was identified for the closest ADH2 gene homolog in the genomes of  Saccharomyces bayanus, Saccharomyces paradoxus, Saccharomyces mikitae, Saccharomyces kudriavzevii,  and  Saccharomyces castellii.  Multiple sequence alignment of the upstream activation sequences (UAS) revealed that nearly all sequences (except that from  S. castellii ) are highly conserved across this region, suggesting a potential for regulation similar to that of  S. cerevisiae  ADH2 ( FIG. 9 , Seq. ID Nos. 36-40). In order to be used for single-step pathway assembly, all promoter sequences must be sufficiently unique to prevent undesired recombination between each other. Therefore, the pairwise identities for each of the  Saccharomyces sensu stricto  ADH2 promoter pairs were analyzed ( FIG. 10 ). The most similar promoter to the  S. cerevisiae  ADH2 promoter is that from  S. paradoxus,  with 83% identity, including a single 40 bp stretch located near the center of the promoter. This homology is significantly less than the 50-100 bp typically used for assembly by yeast homologous recombination, and recombination events between sequences with this level of identity occur at very low frequency, suggesting that these promoters should be compatible with a multi-gene assembly technique utilizing YHR as described above. 
     As with the endogenous yeast promoter candidates, these other putative  Saccharomyces  promoters required detailed characterization of induction profiles. DNA encoding each of these promoter sequences was obtained by commercial synthesis and characterized expression of eGFP from each promoter in the same manner as the endogenous yeast promoters ( FIGS. 11 and 12 ). Of the five  Saccharomyces sensu stricto  pADH2s tested (Seq. ID Nos. 36-40), the promoters derived from  S. paradoxus, S. kudriavzevii,  and  S. bayanus  show timing and strength of expression equivalent to that of  S. cerevisiae  pADH2. In combination with the endogenous yeast promoters, these three additional  Saccharomyces  pADH2s expand the number of strong promoters with the desired induction profile. 
     Expression of Compound Product Pathways Using the Production-Phase Promoter System 
     To study the utility of the new promoter set for heterologous expression of a biosynthetic system, production of fungal derived deydrozearalenol (1) and indole-diterpene (2) was examined ( FIG. 13 , Compounds 1 &amp; 2). The biosynthesis of the indole-diterpene compound the coordinated expression of four in  Aspergillus tubingensis  genes ( FIG. 14 , Seq ID Nos. 59-62). Two versions of each pathway were constructed: one having all production-phase promoters, and the other having all constitutive promoters ( FIG. 14 ). The production-phase promoter system utilized the pADH2 from  S. cerevisiae  (Seq. ID No. 1), pADH2 from  S. bayanus  (Seq. ID No. 38), and pPCK1 (Seq. ID No. 2) and pMLS1 (Seq ID No. 3) from  S. cerevisiae.  In the constitutive system, transcription was driven by four frequently used strong constitutive promoters: pTEF1, pFBA1, pPCK1, and pTPI1 (Seq. ID Nos. 51-54). Each indole-diterpene system was constructed on a single plasmid harboring four expression cassettes: promoter::GGPPS::tADH2; promoter::PT::tPGI1; promoter::FMO::tENO2; and promoter::Cyc::tTEF1; wherein, the promoter sequences corresponded to either the production-phase or the constitutive promoters ( FIG. 13 ). Similar constructs were built for the dehydrozearalenol compound with the two genes HR-PKS and NR-PKS (Seq. ID Nos. 63 and 64). All plasmids were constructed using yeast homologous recombination. It should be noted that pADH2 sequences from  S. cerevisiae  and  S. bayanus  (61% identity) are sufficiently unique for this type of assembly. The production of compounds 1 and 2 produced by  S. cerevisiae  BJ5464/npgA/pRS424 transformed with each of these plasmids were measured over seventy-two hours in YPD batch culture ( FIG. 15 ). An 80-fold and 4.5-fold increase in titer of compound 1 and 2 was observed for the system using the production-phase promoters as compared to the constitutive system. 
     Materials and Methods Supporting the Production-Phase Promotor Experiments 
     General techniques, reagents, and strain information: Restriction enzymes were purchased from New England Biolabs (NEB, Ipswich, 25 MA). Cloning was performed in  E. coli  DH5a. PCR steps were performed using Q5® high-fidelity polymerase (NEB). Yeast dropout media was purchased from MP Biomedicals (Santa Ana, Calif.) and prepared according to manufacturer specifications. Promoter characterization experiments were performed in BY4741 (MATα, his3Δ1 leu2Δ0 met15Δ0 ura3Δ0) while all experiments involving the production of 1 were performed in BJ5464-npgA which is BJ5464 (MATαura3-52 his3Δ200 leu2Δ1 trp1 pep4::HIS3 prb1Δ1.6R can1 GAL) with two copies of pADH2-npgA integrated at δ elements. All Gibson assemblies were performed as previously described using 30 bp assembly overhangs. 
     Construction and characterization of promoter-eGFP reporter strains: All promoters were defined as the shorter of 500 base pairs upstream of a gene&#39;s start codon or the entire 5′ intergenic region. All promoters from  S. cerevisiae  were amplified from genomic DNA, while ADH2 promoters from all  Saccharomyces sensu stricto  were ordered as gBlocks from Integrated DNA Technologies (IDT, Coralville, Iowa). Minimal alterations were made to promoters from  S. kudriavzevii  and  S. mikitae  in order to meet synthesis specifications. In all constructs, eGFP was cloned directly upstream of the terminator from the CYC1 gene (tCYC1). pRS415 was digested with SacI and SaII and a NotI-eGFP-tCYC1 cassette was inserted by Gibson assembly generating pCH600. Digestion of pCH600 with AccI and PmII removed the CEN/ARS origin, which was replaced by 500 bp sequences flanking the ho locus using Gibson assembly to yield plasmid pCH600-HOint. Each of the promoters to be analyzed was amplified with appropriate assembly overhangs using primers 9-92 Table S2 and inserted into pCH600-HOint digested with NotI to generate the pCH601 plasmid series. Digestion of the pCH601 plasmid series with AscI generated linear integration cassettes which were transformed into  S. cerevisiae  BY4741 by the LiAc/PEG method. Correct integration was confirmed by PCR amplification of promoters and Sanger sequencing. 
     For characterization, all strains were initially grown to saturation overnight in 100 μl of YPD media. These cells were then reinoculated at an OD600 of 0.1 into 1 ml of fresh YPD and allowed to grow to OD600=0.4 to reach mid-log phase growth (approximately 6 hrs). 500 pl of each culture was pelleted by centrifugation and resuspended in YPE broth for YPE data while the remaining 500 μl was used for YPD data. The 0 hour time point was collected immediately after resuspension. For each time point, 10 μl of culture was diluted in 2 ml of DI water and sonicated for three short pulses at 35% output on a Branson Sonifier. Expression data were collected for 10000 cells using a FACSCalibur flow cytometer (BD Bioscience) with the FL1 detector. Data were analyzed in R using the flowCore package. 
     Construction of plasmids to produce compounds in  S. cerevisiae:  The sequences for genes assembled on IDT producing plasmids are contained in the supporting information. Regulatory cassettes of promoters and terminators were fused using overlap extension PCR. All genes and regulatory cassettes were amplified by PCR, ensuring 60 bases of homology between all adjacent fragments. 500 ng of each purified fragment was combined with 100 ng of pRS425 linearized with Not1 and transformed into  S. cerevisiae  BJ5464/npgA. Sixteen clones were picked from each assembly plate and grown to saturation in 5 ml CSM-Leu medium. Plasmids were isolated, transformed into  E. coli  and purified prior to sequence confirmation using the Illumina MiSeq platform. Detailed plasmid maps for pCHIDT-2.1and pCHIDT-2c are shown in  FIG. 16  illustrates the primers used and the assembly strategy (Seq. ID Nos. 65 and 66). 
     Examining the productivity of indole diterpene generating systems Plasmids pCHIDT-2,1 and pCHIDT-2c were transformed into BJ5464inpgA with pRS424 as a source of tryptophan overproduction. Triplicates of each strain were inoculated into CSM-Leu/-Trp medium and grown overnight (OD600=2.5-3.0). Each culture was used to inoculate 20 ml cultures in YPD medium at an OD600=0.2 and incubated with shaking at 30° C. for 3 days. Every 24 hrs, 2 mls were sampled from each culture. Supernatants were clarified by centrifugation and extracted with 2 ml ethyl acetate (EtOAc). Cell pellets were extracted with 2 ml 50% EtOAc in acetone. 500 μl each of pellet and supernatant extracts were combined and dried in vacua. Samples were resuspended in 100 μl HPLC grade methanol and LC-MS analysis was conducted on a Shimadzu LC-MS-2020 liquid chromatography mass spectrometer with a Phenomenex Kinetex C18 reverse-phase column (1.7 μm, 100 A, 100 mm×2.1 mm) with a linear gradient of 15% to 95% acetonitrile (v/v) in water (0.1% formic acid) over 10 min followed by 95% acetonitrile for 7 min at a flow rate of 0.3 ml/min. 
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Summary of Sequence Listing 
               
            
           
           
               
               
               
            
               
                 Sequence 
                   
                   
               
               
                 ID No. 
                 Description 
                 Sequence 
               
               
                   
               
            
           
           
               
               
               
            
               
                 1 
                   S. cerevisiae  pADH2 
                 TATCTAAAAATTGCCTTATGATCCGTCTCTCCGGTTACAGCCTGTGTAACTGATTAATCC 
               
               
                   
                   
                 TGCCTTTCTAATCACCATTCTAATGTTTTAATTAAGGGATTTTGTCTTCATTAACGGCTTT 
               
               
                   
                   
                 CGCTCATAAAAATGTTATGACGTTTTGCCCGCAGGCGGGAAACCATCCACTTCACGAG 
               
               
                   
                   
                 ACTGATCTCCTCTGCCGGAACACCGGGCATCTCCAACTTATAAGTTGGAGAAATAAGA 
               
               
                   
                   
                 GAATTTCAGATTGAGAGAATGAAAAAAAAAAAAAAAAAAAAGGCAGAGGAGAGCATAGA 
               
               
                   
                   
                 AATGGGGTTCACTTTTTGGTAAAGCTATAGCATGCCTATCACATATAAATAGAGTGCCA 
               
               
                   
                   
                 GTAGCGACTTTTTTCACACTCGAAATACTCTTACTACTGCTCTCTTGTTGTTTTTATCACT 
               
               
                   
                   
                 TCTTGTTTCTTCTTGGTAAATAGAATATCAAGCTACAAAAAGCATACAATCAACTATCAA 
               
               
                   
                   
                 CTATTAACTATATCGTAATACACA 
               
               
                   
               
               
                 2 
                   S. cerevisiae  pPCK1 
                 ATAGGAAAAAACCGAGCTTCCTTTCATCCGGCGCGGCTGTGTTCTACATATCACTGAAG 
               
               
                   
                   
                 CTCCGGGTATTTTAAGTTATACAAGGGAAAGATGCCGGCTAGACTAGCAAGTTTTAGGC 
               
               
                   
                   
                 TGCTTAACATTATGGATAGGCGGATAAAGGGCCCAAACAGGATTGTAAAGCTTAGACG 
               
               
                   
                   
                 CTTCTGGTTGGACAATGGTACGTTTGTGTATTAAGTAAGGCTTGGCTGGGGATAGCAAC 
               
               
                   
                   
                 ATTGGGCAGAGTATAGAAGACCACAAAAAAAAGGTATATAAGGGCAGAGAAGTCTTTGT 
               
               
                   
                   
                 AATGTGTGTAACTTCTCTTCCATGTGTAATCAGTATTTCTACTTACTTCTTAAATATACAG 
               
               
                   
                   
                 AAGTAAGACAGATAACCAACAGCCTTTCCCAGATATACATATATATCTTTATTTCAGCTT 
               
               
                   
                   
                 AAACAATAATTATATTTGTTTAACTCAAAAATAAAAAAAAAAAACCAAACTCACGCAACTA 
               
               
                   
                   
                 ATTATTCCATAATAAAATAACAAC 
               
               
                   
               
               
                 3 
                   S. cerevisiae  pMLS1 
                 CCATTGGGCCGATGAAGTTAGTCGACGGATAGAAGCGGTTGTCCCCTTTCCCGGCGA 
               
               
                   
                   
                 GCCGGCAGTCGGGCCGAGGTTCGGATAAATTTTGTATTGTGTTTTGATTCTGTCATGAG 
               
               
                   
                   
                 TATTACTTATGTTCTCTTTAGGTAACCCCAGGTTAATCAATCACAGTTTCATACCGGCTA 
               
               
                   
                   
                 GTATTCAAATTATGACTTTTCTTCTGCAGTGTCAGCCTTACGACGATTATCTATGAGCTT 
               
               
                   
                   
                 TGAATATAGTTTGCCGTGATTCGTATCTTTAATTGGATAATAAAATGCGAAGGATCGATG 
               
               
                   
                   
                 ACCCTTATTATTATTTTTCTACACTGGCTACCGATTTAACTCATCTTCTTGAAAGTATATA 
               
               
                   
                   
                 AGTAACAGTAAAATATACCGTACTTCTGCTAATGTTATTTGTCCCTTATTTTTCTTTTCTT 
               
               
                   
                   
                 GTCTTATGCTATAGTACCTAAGAATAACGACTATTGTTTTGAACTAAACAAAGTAGTAAA 
               
               
                   
                   
                 AGCACATAAAAGAATTAAGAAA 
               
               
                   
               
               
                 4 
                   S. cerevisiae  plCL1 
                 ATTTATTGAAAAGTAAATATCTCGTAACCCGGATGCTTTGGGCGGTCGGGTTTTGCTAC 
               
               
                   
                   
                 TCGTCATCCGATGAGAAAAACTGTTCCCTTTTGCCCCAGGTTTCCATTCATCCGAGCGA 
               
               
                   
                   
                 TCACTTATCTGACTTCGTCACTTTTTCATTTCATCCGAAACAATCAAAACTGAAGCCAAT 
               
               
                   
                   
                 CACCACAAAATTAACACTCAACGTCATCTTTCACTACCCTTTACAGAAGAAAATATCCAT 
               
               
                   
                   
                 AGTCCGGACTAGCATCCCAGTATGTGACTCAATATTGGTGCAAAAGAGAAAAGCATAAG 
               
               
                   
                   
                 TCAGTCCAAAGTCCGCCCTTAACCAGGCACATCGGAATTCACAAAACGTTTCTTTATTA 
               
               
                   
                   
                 TATAAAGGAGCTGCTTCACTGGCAAAATTCTTATTATTTGTCTTGGCTTGCTAATTTCAT 
               
               
                   
                   
                 CTTATCCTTTTTTTCTTTTCACACCCAAATACCTAACAATTGAGAGAAAACTCTTAGCATA 
               
               
                   
                   
                 ACATAACAAAAAGTCAACGAAAA 
               
               
                   
               
               
                 5 
                 
                   S. cerevisiae 
                 
                 CAAAAAAACAATGGAAGAACAAAGAAAATTTAGCGGAAGTAAAAATAACAGCCGAAAGC 
               
               
                   
                 pYLR307C-A 
                 CAAATTCAGGCTTATCTTGCCTACTCTTTCTTTTATCGAATTCCTTTAGGCCGTTGCAAT 
               
               
                   
                   
                 AGAAAAGTAATAAAAACGCATATACGTAAGTTGTAGTCAGTGTAATTGCAATCTATTATG 
               
               
                   
                   
                 CGCATCAGGTGCGCATACTACATCCATTGGTGCACAAAAAAAGGAACGCAGACAAGAA 
               
               
                   
                   
                 AATTATTCAGTTTGCTGTTCGTGATGAGCCATCCCTGAATATGACTAATGTTAATGTTCA 
               
               
                   
                   
                 ATTTGGGATCTTATTTTTTTTTGTGCAGTAATAAGAATCTTTGAAAAAAAACTATATAAGC 
               
               
                   
                   
                 CTATATAGTTTGTAAGATATAAGACAAAACACACCTGCTTTTCCACTACACATTTTCGTT 
               
               
                   
                   
                 ATTATATAAAAAAGACAGCCAAGTATACTTGTCAACAAAATAAACTCATAGCAATTACAC 
               
               
                   
                   
                 TATAAAAACAATAGCATCAAAA 
               
               
                   
               
               
                 6 
                 
                   S. cerevisiae 
                 
                 TGGCAATCCCCTCCGATCGTCCGCGGCAAAATGGTCGTCAATCGGACAAAGGGGGAT 
               
               
                   
                 pYGR067C 
                 GATGGGATCTGGTAATAGAAGAAAATATGGACTAAAGGTAGCCGCTAAAGCGATCCAG 
               
               
                   
                   
                 GCATGTGTTGCCAATGATGTAAGTCAAGCGAAGGAAATGGTTCAGTAATATGATAGACA 
               
               
                   
                   
                 GACTGCACTTCAAGGGTGCGCCCCCTCCCCCGCGCATATGCTTACAACGCAAAAT/stAT 
               
               
                   
                   
                 TGACGTTTAATGTGGATACTTATCGTAATCGCTGCATTATAGATTTCGAGTCATGTTCAC 
               
               
                   
                   
                 TTAACCCCACATATTTATATAGAACGCATCTTCAAAGTACTTATAAAGTTTAGTTTTACAT 
               
               
                   
                   
                 TTTTCTGCTTTCTATTTCTTCTTTTTCGGTTCTTCTTCATGCCAGTTGGCATGGCTTAAGA 
               
               
                   
                   
                 GCTTTACTTGTCGCTTTTATTTAAAACCTTCTCTCGGGAGAAGACAATTGTTGATATACA 
               
               
                   
                   
                 GTAATTGTATTTGCATTATCACTGCT 
               
               
                   
               
               
                 7 
                   S. cerevisiae  plDP2 
                 AACGTCTATCTATTTATTTTTATAACTCCGGGATGTCATTGCCGGTGGTCCGAAAATCG 
               
               
                   
                   
                 GCAAATAAGGAAATAAGGGAAGAATATGCAGTAGTCAAATCATCAGTGTTCTCTTTGAT 
               
               
                   
                   
                 ACCTTTCAGGGCTAGGAATAGTGGGGGTGGAGTATAATATCAAAAACCGGACTTAACAT 
               
               
                   
                   
                 TATTGGTTCGGTTGGAATTGGCTATAGGCAAACTAGTCTCCGGCATGATATATAAATGA 
               
               
                   
                   
                 CAGCCTGCAATTGTATGTTACTACACTCTTGACTTGTCGACTACAGTCGCTGCTCAGGC 
               
               
                   
                   
                 ACGAGAATAGGAGGTAAGAAGGTAACGTACGTATATATATAAAATCGTA 
               
               
                   
               
               
                 8 
                   S. cerevisiae  pADY2 
                 GAGCTCCGTGGAATAGGCGAGCGGCTGAGTGGTTCTCCAAGCTACGGTTTTTACGTGT 
               
               
                   
                   
                 AGCCCCATGTGAGCAAGCCAAACAAGGGCCCTTAAAGGCGTGACTACAAAAAGGGGC 
               
               
                   
                   
                 GGGTTGGAAGGTCATCTGCAGCGAGATACGAAAAGATTTTTTGCCAGATTTGCGGTTG 
               
               
                   
                   
                 GGCGGCTATTTCGGTATTGTTGGGGTAACAAACGTTGGGGAAGACTGCATTTTCTTACA 
               
               
                   
                   
                 GCTTTTTTTCGTTATCGCGGGTTGGGCGGCTATGGCGCCTTCTCCTCTGTACTCCAACC 
               
               
                   
                   
                 TGTCAGAGACACCAAGCTGTATATAAAGCACCTTGGTTGGATCGTATTTCCCTGAGATC 
               
               
                   
                   
                 TTGCTATAGGTTCATTTTATATATCGTCCAATAGCAATAACAATACAACAGAAACTACTA 
               
               
                   
                   
                 GCATCTGTTTATAAGAAAAAGGCAAATAGTCGACAGCTAACACAGATATAACTAAACAA 
               
               
                   
                   
                 CCACAAAACAACTCATATACAAACAAATAAT 
               
               
                   
               
               
                 9 
                   S. cerevisiae  pGAC1 
                 CCCTATCTTTTTTTTTTTCTCGCAATCTGGGGAAAGCTTTTCTCATGCTTATACGTGATTT 
               
               
                   
                   
                 GTTATATAAGGGATTGCTATTTCAGGCATCATTCACCTCCTTTTGTATCCTTAGTTTCAC 
               
               
                   
                   
                 TGCATTTGATATATATATATACGTATCTGTAGTTTCCTTCCATTACATAACGCATAATATA 
               
               
                   
                   
                 CTATTTCCATAGTCTATCTTACATCTTTTTTCTTACTTTTGTTAAGGAACGGATAACGATA 
               
               
                   
                   
                 AAACAAAAAGAGAGATTTAAGATTACTTCTGTAACTTTTTTGATCCATTACCAAAACTATA 
               
               
                   
                   
                 TTTTTTTTCTTTTCTCTCCTCTGGCATTAAACACAGTTATTGCTACAGCTAATCATCGATA 
               
               
                   
                   
                 TAATAATACATCACATTAACTGTCTATAAGAGGCTGGTACTTAGTAGATGGTGAGAATTT 
               
               
                   
                   
                 TTTATTTTTGTATTTTAACTTCATTTTTGTAAACAAGTTTGGAACTGGAACTTACTATAGAA 
               
               
                   
                   
                 CAAGAGCTTAAACC 
               
               
                   
               
               
                 10 
                   S. cerevisiae  pECM13 
                 GTTGTATCCTATTGGATCACGGGCGACGGACAAGACCCGAAGTGCGGACCGGCATGG 
               
               
                   
                   
                 TCAGCTTGCACGGAAGCTTTAAGGGTTTCCCTTGTTTCGGCATTAGAAGAGGCATTTCG 
               
               
                   
                   
                 CACGTTTTACCGGGTCAGAAACTTCGAGGAAGCTGTGACAATTGGAAAAAAAGGCAAA 
               
               
                   
                   
                 ACTAAATGCAATGTATCCGGTTGCCCATGCATTATTTGTGATGTTTTCGGATGTAGTTCG 
               
               
                   
                   
                 CTGCGCTCCGCGGCGATATATCCTCTAGCGAGAGGCATATGTATAAATATATATATATA 
               
               
                   
                   
                 TATCTAACAAAAGCATTCAAGTTTCTTTCTCTGGTGTTACGTCTTTGTTCGACTTTCTCT 
               
               
                   
                   
                 GCTTACAGCCCTGTATGACCAAAGAAAAAATAAAAAGACAGCTACATACCAGCAGAAAT 
               
               
                   
                   
                 TTTTTATAGTATTACACTATACATCCAAGTTTTTTCACAATTATTTATTGTTTTTCTCACAT 
               
               
                   
                   
                 AGAAAATTCCGCATACTGCGATTATA 
               
               
                   
               
               
                 11 
                   S. cerevisiae  pFAT3 
                 GAAAGCTTATTACTGAGTTTTGCGGAGCATCGCTCGGAGCGGCGGAATTGAATCGAAC 
               
               
                   
                   
                 CGCCGTGCTATTACCGAACAAAAAAATTCGAAAGCATAAACTCAGTAGTGAAAAACTTG 
               
               
                   
                   
                 AGAATTTTCAGATGAGTGGCGACTTTCCAGTCCTTGCGGTTTTGTCACCTTAGTCAGCT 
               
               
                   
                   
                 AGTAAGGAGGCCGTGTGGGTTAGAGTGGCTACAATCCTCAAAGGGCACTTCTAGAACC 
               
               
                   
                   
                 CACGGTGAATTTTTTTTGGCATGATAAATCGGTAGAATCGGTGAAGTAATTACCCAAAA 
               
               
                   
                   
                 AAGGATCGGGATTGTGTTTCTCGTAATTCCGTATTATTGCCGATGGCATCGACTACTTC 
               
               
                   
                   
                 TTTTTTCAGAAACCCCAACAAGGGTCTATTGTAATTGTATATAAACCTTTTTGTAATGGAT 
               
               
                   
                   
                 ATATACATGTGGTACTATTTCTCCTCATCCTGCTCCATCGAAAATCCTCATACGAAGAGT 
               
               
                   
                   
                 TAGGAAAGCAAAGAAAACAACAAAAAC 
               
               
                   
               
               
                 12 
                   S. cerevisiae  pPUT1 
                 AGACACAATGCGAAAAATCGCGCAGGGACATAATTTTTGTTTTCATTATTCTTTCGCTTA 
               
               
                   
                   
                 TTCCCTCCGTTAGCTCCACCGCTTTTTTGATTGGAATTTCCTTTCGGCAATGGCTTTCC 
               
               
                   
                   
                 GGTTACCACGCCTCGGGTTTCGCATCCCGAAAAGCATATCTACACAAGAAAAATGAATG 
               
               
                   
                   
                 ATAAACAATTGATGAGTGGCGCTATTTCCCTTATCATCTCATTATTGTACTTAGTATCGT 
               
               
                   
                   
                 CTATTATCAGGAGAAATCGCATGAACTAAGCCCATTTTCTCACCCTTCTGCCTTCTTATA 
               
               
                   
                   
                 TAAAGCTTGCTGGGAACCGAACACAAACTCCACAAGTCCGTAGCAGCTCTTCTCTTTTG 
               
               
                   
                   
                 TCTTTTATATATCATAAACATCGCTACATAGTAATAACACTAACGCACGCTAGAA 
               
               
                   
               
               
                 13 
                   S. cerevisiae  pNQM1 
                 AGGGGTAGCGGCTTTTTCATCAACTCGATTATTACCCTTTAGAGACCTTCCCTAAAGTG 
               
               
                   
                   
                 AGCGGCAATTATTTCCGGATGTTAGTAGGGTAATATGGTTACGGATTTGTGACACAAAA 
               
               
                   
                   
                 GGGCTTTTCAACAGTCGGTCTGGGTTGAAGGATTTTCAGGATGACGAAGCTTTCAATAA 
               
               
                   
                   
                 GAGGGACTGGACTGTTAACGCGGGGAATTATAGGTTACTTTCCTTGATCTGGCTCTGG 
               
               
                   
                   
                 CTCTGGCTCTGATTTTGGCTCTTGTACTCCTCGGACTTCTTGACTTGTAACGAAATACG 
               
               
                   
                   
                 TCTTTTGTCCTTCTCTTCTTCTTCCATAGTAGGGGCGAATGAGGGGAGCATAGTGGATC 
               
               
                   
                   
                 CTTCTAACCATCTAGAATGGGGTGGACAACATATAAAAGAAGAGCAATCTTGCAGCGCA 
               
               
                   
                   
                 GTCATATTTATGCTAAGTATATCATTATTTCTTGCTAGCGTAAGTCATAAAAAATAGGAAA 
               
               
                   
                   
                 TAATCACATATATACAAGAAATTAAAT 
               
               
                   
               
               
                 14 
                   S. cerevisiae  pSFC1 
                 AGCCTAGTCCCGGTAAACCGCAAACGGACCTTAATTGTGACGAAGGGCCCAAATTTGA 
               
               
                   
                   
                 TGGGTCGGTGTTAATGATTAGTCCTCATTGTCATAATAAAGTGTGATGATGGAGGCAAT 
               
               
                   
                   
                 GATGATATACGGTAGTACTACTGCTCGAGGTGCTATCTTTTAACCAATCCTTTGAGATTC 
               
               
                   
                   
                 TTGTCGCCACGGAGTTACTACCTTTTACAAACCGTAATGTCACATTTTGCATATATCTTA 
               
               
                   
                   
                 TGTATAAATATATAGTTCACTTACTACTTGTTCTCGTTTTGTTAACTTTCTTGTTGTAGTT 
               
               
                   
                   
                 CTTCTTGTTCTTGGCGTTTCCCCCTTTGTTTTCTATCTGCTTCATAAGTAAAGTGCAAAG 
               
               
                   
                   
                 CATTTTGGAAGATATTATCAATTGAGTCATTGAAAGAAACTTGGCATCTTCCCTATTACT 
               
               
                   
                   
                 AAAACTAAGAATACTTGATTCAAGAAAGAAGTTTATATTAGTTTTAGCCGTAAGATAACA 
               
               
                   
                   
                 TAACAAAGAAGAAGAAAGAAAA 
               
               
                   
               
               
                 15 
                   S. cerevisiae  pJEN1 
                 TCGATCAGCTCCAATTAAATGAAGACTATTCGCCGTACCGTTCCCAGATGGGTGCGAAA 
               
               
                   
                   
                 GTCAGTGATCGAGGAAGTTATTGAGCGCGCGGCTTGAAACTATTTCTCCATCTCAGAG 
               
               
                   
                   
                 CCGCCAAGCCTACCATTATTCTCCACCAGGAAGTTAGTTTGTAAGCTTCTGCACACCAT 
               
               
                   
                   
                 CCGGACGTCCATAATTCTTCACTTAACGGTCTTTTGCCCCCCCTTCTACTATAATGCATT 
               
               
                   
                   
                 AGAACGTTACCTGGTCATTTGGATGGAGATCTAAGTAACACTTACTATCTCCTATGGTA 
               
               
                   
                   
                 CTATCCTTTACCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAATCAGCAAAGTGAAGTAC 
               
               
                   
                   
                 CCTCTTGATGTATAAATACATTGCACATCATTGTTGAGAAATAGTTTTGGAAGTTGTCTA 
               
               
                   
                   
                 GTTCCTTCTCCCTTAGATCTAAAAGGAAGAAGAGTAACAGTTTCAAAAGTTTTTCCTCAAA 
               
               
                   
                   
                 GAGATTAAATACTGCTACTGAAAAT 
               
               
                   
               
               
                 16 
                   S. cerevisiae  pSIP18 
                 ACATAGTACTGTACGATTACTGTACGATTAATCTATCCACTTCAGATGTTCAACAATTCC 
               
               
                   
                   
                 TTTTGGCATTACGTATTAATACTTCATAGGATCGGCACCCTCCCTTAAGCCTCCCCTAAA 
               
               
                   
                   
                 TGCTTTTCGGTACCCCTTTAAGACAACTATCTCTTAACCTTCTGTATTTACTTGCATGTTA 
               
               
                   
                   
                 CGTTGAGTCTCATTGGAGGTTTGCATCATATGTTTAGGTTTTTTTGGAAACGTGGACGG 
               
               
                   
                   
                 CTCATAGTGATTGGTAAATGGGAGTTACGAATAAACGTATCTTAAAGGGAGCGGTATGT 
               
               
                   
                   
                 AAAATGGATAGATGATCATGAATACAGTACGAGGTGTAAAGAATGATGGGACTGAGAG 
               
               
                   
                   
                 GGCAATTATCATCCCTCAGAATCAACATCACAAACATATATAAAGCTCCCAATTCTGCCC 
               
               
                   
                   
                 CAAAGTTTTGTCCCTAGGCATTTTTAATCTTTGTATCTGTGCTCTTTACTTTAGTAGAAAG 
               
               
                   
                   
                 GTATATAAAAAAGTATAGTCAAG 
               
               
                   
               
               
                 17 
                   S. cerevisiae  pAT02 
                 AAGTTCTTGACTACCCCTATCTCACACTAGTACGTAATTCAATGTATCATTCGTATTGTA 
               
               
                   
                   
                 AGTAGATAGAGACGCAATACAGGAAAGCTGACCTTCCTTCCAATCACCACGGCTGAAA 
               
               
                   
                   
                 TGCTTTGTTGACCAATTACGGACGCTTAAGAGCGGACGCGGCTGGAACGGCTCCATCC 
               
               
                   
                   
                 TAAATCGGCGGAGGGAGAACTCCGATACCAGCCGACATGGCAATAATAGTGACAGTAG 
               
               
                   
                   
                 ATGCTACCAGCCCCGCAATAATTTCACAGTAGATCATCAACAGTCTCCTCATTTCTGGA 
               
               
                   
                   
                 AATGATCAGCAACTTCGACGGATTTAACTCTCAAGCAGTTACGCACTCCGAGAACAGCC 
               
               
                   
                   
                 GTGATCATCTTTGAACAAGCAAAATATATAAAGCAGGAGAACTGTCCTACCTAGAGCTA 
               
               
                   
                   
                 GAATAGCCATAACTAACTATGTAACATTCTACAGATCAATCAAAAACAATCTTCAATCAC 
               
               
                   
                   
                 AGAAAAAAATAAAAGGC 
               
               
                   
               
               
                 18 
                   S. cerevisiae  pYIG1 
                 TTTTCTAGTTCTTCTTCTGCAATATTGCCTTTTGGGAAGAAGGATCGAAAGTAGCCATTT 
               
               
                   
                   
                 GCAGACACGTTTTTACTATATTTACTGTATCTTCGATTGCGCGGCTAAAGTTGCCATATT 
               
               
                   
                   
                 ATTATTATATTGCAGCTCAACCCCGCATTTCCGGAGTTTTCTTTTTTTTTATTTGGGGTAA 
               
               
                   
                   
                 TTTGGAGGTCGGCGGCTATTGGTGGGGCCGGAAATGGTGACACACTTGTAATATATAAG 
               
               
                   
                   
                 GAGGAAATCCTACATGTGTATAAGCGAAATCACAAGGATAATAATGTATTGCTAAACAC 
               
               
                   
                   
                 CCTCAAGAAAGAAAATAATCATAACGAAATC 
               
               
                   
               
               
                 19 
                   S. cerevisiae  pFBP1 
                 CGGATGGAATCGCCGCTTTTGAATTCACCTCCGGGGTATTATTATTATTCTTAGTAGTC 
               
               
                   
                   
                 GCGGTCGTGCGGACACCCGGAGTTATGCGGGCCCGAAAGCTCATTATGTAGTAAAGC 
               
               
                   
                   
                 TAGGTAATGTTAAGGGCGTAAGAGCCAACGCAAGGCAGCAATAGCCTGGTATTCCCAC 
               
               
                   
                   
                 ATATCAAGAAAGCTTAAAAAGTTGAGACAGGGAATTTGAAGGCGAAGATTGCCGAACT 
               
               
                   
                   
                 GGCCAATACCCACTACTTTTTTTTTGGTTTGCTTGGTTTCTTCCTGTCGCTTGCCAACTT 
               
               
                   
                   
                 GTGGCATCTTCCCCACACTATATTATAAGGATCGTCCTATGTATAGGCAATATTATCCAT 
               
               
                   
                   
                 TTCACTCGCTAACAAATGTACGTATATATATGGAGCAACAAGTAGTGCAATTACAGACG 
               
               
                   
                   
                 TGTATTTTGTCTTGATCTTGCTTTTTGTATGATAGGCCTAAGAATAACAGTGCGAACATA 
               
               
                   
                   
                 TAAGAAACATCCCTCATACTACCACACAT 
               
               
                   
               
               
                 20 
                   S. cerevisiae  PHO89 
                 AGACCTTTTTTTTCTTTTTCTGCTTTTTCGTCATCCCCACGTTGTGCCATTAATTTGTTAG 
               
               
                   
                   
                 TGGGCCCTTAAATGTCGAAATATTGCTAAAAATTGGCCCGAGTCATTGAAAGGCTTTAA 
               
               
                   
                   
                 GAATATACCGTACAAAGGAGTTTATGTAATCTTAATAAATTGCATATGACAATGCAGCAC 
               
               
                   
                   
                 GTGGGAGACAAATAGTAATAATACTAATCTATCAATACTAGATGTCACAGCCACTTTGG 
               
               
                   
                   
                 ATCCTTCTATTATGTAAATCATTAGATTAACTCAGTCAATAGCAGATTTTTTTTACAATGT 
               
               
                   
                   
                 CTACTGGGTGGACATCTCCAAACAATTCATGTCACTAAGCCCGGTTTTCGATATGAAGA 
               
               
                   
                   
                 AAATTATATATAAACCTGCTGAAGATGATCTTTACATTGAGGTTATTTTACATGAATTGTC 
               
               
                   
                   
                 ATAGAATGAGTGACATAGATCAAAGGTGAGAATACTGGAGCGTATCTAATCGAATCAAT 
               
               
                   
                   
                 ATAAACAAAGATTAAGCAAAA 
               
               
                   
               
               
                 21 
                   S. cerevisiae  CAT2 
                 TCCGAAGAGCGTGCTACCAATTCTTCATCTCGTTAACAAACTGGTTCTCCGTTAAAAATT 
               
               
                   
                   
                 GTGCTATATGTCCTATAAGCCAACTCTATCTATATCTTTTCTTTTAGTCCTACTTTGGATA 
               
               
                   
                   
                 CTGTTACCACCATTTTAGATTGCTTTTTCTTTTGCCGCTAGCCTTACAATATTTGGCAAA 
               
               
                   
                   
                 CTTTTTTTTTTTAGCCGCCGAGACTCTTGATCTATGGCCGGGCGAAAGGGCAAATGACT 
               
               
                   
                   
                 GCTTATCCCCGCCATCACTTCCCCCCGCCCAAGGGTTTAGAATTGGGGATTAAGTAAA 
               
               
                   
                   
                 AACGAATGACTATTCCTCTCAAAGTCATCCTTGTTCGACAAAAAGAATGGAATATAACAT 
               
               
                   
                   
                 ATTGGAACAATTTCATCCTCTTTTCCCCATTTTCGCATATAAGAGCAACTAAACGCCGGT 
               
               
                   
                   
                 GAGTAAAGTGCCCTTCCCTACAGACTCTTTTACTCAGGTATATATATATATATATCCCTT 
               
               
                   
                   
                 AAAAACTAAAAAGAAAGCACTC 
               
               
                   
               
               
                 22 
                   S. cerevisiae  CTA1 
                 AGCGGTTGTTCTAACCACTATTTAAAGCCGCAATTAGTAATGCAAAAAGTTGGCCGGAA 
               
               
                   
                   
                 TTAGCCGCGCAAGTTGGTGGGGTCCCTTAATCCGAAAAAGGACGGCTTTAACAAATAT 
               
               
                   
                   
                 AAACTCCGAAAATCCCCACAGTGACAGAATTGGAGAAACAACCAGTTTTGATATCGCCA 
               
               
                   
                   
                 TACATATAAAGAGATGTAGAAAGCATTCTTCACTGTAATGTCCAAATCGTACATTTGAAT 
               
               
                   
                   
                 TTCTTGTAGGTTTATTTAAAAGGTAAGTTAAATAAATATAATAGTACTTACAAATAAATTT 
               
               
                   
                   
                 GGAACCCTAGAAG 
               
               
                   
               
               
                 23 
                   S. cerevisiae  iCL2 
                 AATTTTTATTTTCTCCTTCCATATGAGCGACAGCGGTTACTAGCCGCTGTCCTCAGGTTA 
               
               
                   
                   
                 ATGATCCAAGTCCGAGATCCGGGCCGAATATGCTTGCGGGGAAAGAAATAAAAGTGCA 
               
               
                   
                   
                 TTGGAGAAGAAAAGGATATGCTCTTCAATTAGAAGCGCCGAAACACTAACATCATGCTA 
               
               
                   
                   
                 GCGATATCATACGTACACTATATAATGTAAAAAATGGGCTTAAGAATAACTCTCTTATTT 
               
               
                   
                   
                 CTTAACTTTTGTTGCGGTTGAAGAGCTTATAAAAGTACTAGTGGCCTAAAGAAGCTACA 
               
               
                   
                   
                 GCGCCGATAATAATATCGATTTCGACTTTTCTAGTATTTCGCCG 
               
               
                   
               
               
                 24 
                   S. cerevisiae  ACS1 
                 TGTGCACATACGTCCAGAATGATATCAAGATAAATGGCACGTGTATGTACGGCTGTGTA 
               
               
                   
                   
                 AATATGATAATCATCTCGGACGAACGGCGTAGCACTCTCCATCCCCTAAAAATGTTCAC 
               
               
                   
                   
                 GTGTGACTGCTCCATTTCGCCGGATGTCGAGATGACCCCCCCCCCTCAAAAGGCACTC 
               
               
                   
                   
                 ACCTGTTGACATGCCGTGGCAAATGATTGGGGTCATCCTTTTTTTCTGTTATCTCTAAGA 
               
               
                   
                   
                 TCCAAAGAAAAGTAAAAAAAAAAGGTTGGGGTACGAATTGCCGCCGAGCCTCCGATGC 
               
               
                   
                   
                 CATTATTCAATGGGTATTGCAGTTGGGGTACAGTTCCTCGGTGGCAAATAGTTCTCCCT 
               
               
                   
                   
                 TCATTTTGTATATAAACTGGGCGGCTATTCTAAGCATATTTCTCCCTTAGGTTATCTGGT 
               
               
                   
                   
                 AGTACGTTATATCTTGTTCTTATATTTTCTATCTATAAGCAAAACCAAACATATCAAAACT 
               
               
                   
                   
                 ACTAGAAAGACATTGCCCACTGTGCT 
               
               
                   
               
               
                 25 
                   S. cerevisiae  PDH1 
                 AATATAAATAAAATTCCATACAGCATGTCTAATCATAGCTAATTTATACATATTCATCATG 
               
               
                   
                   
                 AAAACATATAGGGGAAAATATGGTCGGTTAACACACCTATCAAAAAATTATTCAGCAATT 
               
               
                   
                   
                 CCAATCTCGTTAGTAAAATATATTCTTATTTTTTTTTTTTTTCTCTGATTGTATTATTTCTG 
               
               
                   
                   
                 GAGTTTTGACTTATTTTTTTACCACATCGCGCTTTTCGTCCCCAATCTCTCTGATATATG 
               
               
                   
                   
                 ATGCTGTCTATAGGTAGCCACTTCCCCGATGTCGGACCTCGGGCCGTTTACAAACTTTA 
               
               
                   
                   
                 TTGAGATGACCTTATTTCTCCACATTCTAGTCATTCAACTTTTACCCTCATATGTTTACCT 
               
               
                   
                   
                 TCACTAATGTGAAAGCATGACCAAAGAAAGTGTATAAGGTATATAAATCTGCCATAATGT 
               
               
                   
                   
                 ATGTATAACTTATTAGGACTTTCTCAAATAGTATTTTGGTATTTTCTACTGTTCTCTGATG 
               
               
                   
                   
                 ATCGAGAGCAAACAGA 
               
               
                   
               
               
                 26 
                   S. cerevisiae  REG2 
                 AAGTACGATATGGTATAACTGTAACATTGAAGGACTGAAGGACTGAAGGACTGAAGGA 
               
               
                   
                   
                 CTATAGTCAAGGGCCAATGGGGAAGGTCCCTTCCAGGCCATTTGCCCGATAGTTTGTC 
               
               
                   
                   
                 CTTCTCTTGCTTTTCCGACGGCCCGATTGCATGTGGCGGGGCAGCACTGGATAAAAAA 
               
               
                   
                   
                 ACGTGGGGGGAGTGATTAAATTTATACGCTTATTGTGTCAACACGGAAACCTTATAGTT 
               
               
                   
                   
                 ATCATTACTAACATCGCAACAAGCTGCTTTTTTACTCGTTTTTAGCCACACCATACCCCC 
               
               
                   
                   
                 TTTAATTAACTAATAATGCATAAAATAGTTATTGCTTCTTGAGTTGCAGCTTCTTCCTGGA 
               
               
                   
                   
                 CGTACTGTTATATATGGCATGTCTTCGCATGTCCGTCAAATTTAGCGTTGTCTCGAAACT 
               
               
                   
                   
                 TAGGCTGTCGTTCTTGCTGTCTGTCTTCTGATAAAATAATATATTGGAATAAGAAAAAAA 
               
               
                   
                   
                 AAATAGGAACAAGAAAGTGTGTGAGA 
               
               
                   
               
               
                 27 
                   S. cerevisiae  CIT3 
                 ATATTATTCAGTTGAAAGACAAAAAAACATAAATATTTCTATGAGCAAACAATTTGAACA 
               
               
                   
                   
                 GAAAAATAAAATTGGGGAAGTGACACACCATGGTAGCGGTTCTAAAGCGAAATCGGCA 
               
               
                   
                   
                 AAGCGGCTAAATAGCAGTTTTGATGACTTACTCCACACTGAAAATGGATGACCTTAAAT 
               
               
                   
                   
                 AGGAGATAAAGCTTTTTCATCCCTATGTATTTAAGATGACTGGCTTGTCAAGCATTCTAA 
               
               
                   
                   
                 TCATAAAAAAAAGATCGTATTTGATCAAGAATTTATACATAGACGCCGCTAAATAATTGA 
               
               
                   
                   
                 ATACAAA 
               
               
                   
               
               
                 28 
                   S. cerevisiae  CFRC1 
                 CTCGTTTGCCGTTACATTGCATTGATGGTACAATAAAGGGCATGCTTTATATCGAGATG 
               
               
                   
                   
                 TTTCAGTGTATATGAGGGGAAACAGAAAAGAGTCATTCCTGCCATTTTTTGGTCACTGC 
               
               
                   
                   
                 TTTTTCTGCTATGAGTAATGGTGAAGTTCCTTGTGGCTACACGCTTAATGTCATCGGGT 
               
               
                   
                   
                 TACTGCTCCTAATATCCGCATATAAGCTTTATGCAGGGATCAGTTGGGCGGCTATTTAT 
               
               
                   
                   
                 CTACACCCAGTCATCCGGCGTGACTGGATCTCCACTTGCCGCAATAAGTCGGTGGACA 
               
               
                   
                   
                 AATGGAGATTTAAGAGTAAAGATGCATGATGGTATAATTCCTTTAGTCGAAATAGATATA 
               
               
                   
                   
                 TTTCAAGCGCATATATAGGCAGACGCTTGTACTGTAGAAATAGCCGATATTCAATTGCG 
               
               
                   
                   
                 CTCTATGTGTGTTTTTATTCCAGGTTTTCCTTGGATTCTACGTATTGTACGACTTTCTTAT 
               
               
                   
                   
                 CCTCCACAAACGTCATCGTGTCAGTA 
               
               
                   
               
               
                 29 
                   S. cerevisiae  RGI2 
                 CCCAACAGATTTCAAGTCTGTCGCCTTAACCACTCGGCCATAGTGCCTAAAACAATGTA 
               
               
                   
                   
                 GGTTATTTAAGCAAGTATTGTAGATACTTTTCGTAATAAACTACAATGCACCCACGACTC 
               
               
                   
                   
                 GCGGTGTAATGATGGCATGAAATCATTGAACGAAGTTTTGCGGCTATACGGCTGAAGG 
               
               
                   
                   
                 ACGAGACTAAAGGGACAGGAATTATTAATGCGGGGTATAATTTGAATAGTATTAACGGG 
               
               
                   
                   
                 CACTGCCGTTTAGCCATCAAATGCTATTGTTGGGGTATTCTCTCTACTTTTTGTTCTTGG 
               
               
                   
                   
                 CTTGAACCTTTTCGGCGGTTGGCAATCGTCCGTATATAAGCATCGGCTGTCCCAATCCT 
               
               
                   
                   
                 CTATTGCCCTTTTCCCTTGCACCTCCTTCTCAATTCTTCGTATCTTTCGCGTAAAGGTAG 
               
               
                   
                   
                 ATCTTGATTCACCTATCTGTCGAAACACGATTAAGTGCAAACGAAACAACGTACAGTAT 
               
               
                   
                   
                 ATAACAAAGTATTTTAAATAATAAGA 
               
               
                   
               
               
                 30 
                   S. cerevisiae  PUT4 
                 GCTATGACGTTTGGGTGGCCTAGCCGGTTCGCGTGTGCCTGTCGCTTTTGTCGCTTTT 
               
               
                   
                   
                 CAACTTCTGCCCGATATTTCCTATCAAAGGAAAATGGGACGTTTTCAACCCCTCGCTAT 
               
               
                   
                   
                 CATCGTGCCTGCACTCTGCCTATCGCCAACTACACCGGGGTTTTATCTGCTTCACCCCT 
               
               
                   
                   
                 CCATCCAGTGCTGATAACAAGAAGAACCTTGCAGGGTAGGGCAGGACCTACGGCCAAA 
               
               
                   
                   
                 ATACTAATTATGTCTGTTTATGTACATGCCCAATCTGAATATTCCATGAATGTAGGCAC 
               
               
                   
                   
                 AGCATATCTCCATCCATGTACTGATACAGACGCATAAACATATATGTATATACATACTTA 
               
               
                   
                   
                 TACACTCGAATATTTGTAGACTGATGTACTTCTATATATATATAGGGGGTTTGTGTTCCT 
               
               
                   
                   
                 CTTCCTTTCCTTTTTTTTTCTCTCTTCCCTTCCAGTTTCTTTTATTCTTTGCTGTTTCGAAG 
               
               
                   
                   
                 AATCACACCATCAATGAATAAATC 
               
               
                   
               
               
                 31 
                   S. cerevisiae  NCA3 
                 TAGATGCGCCATCTCCGAGAAAAAATCTAGACAATAACAGCGACAATTAACCTAAAGAG 
               
               
                   
                   
                 GATAGAAGATCGAGCAAAAAAATTTTTTTAATATGGGGTCAGTGGCGATATTATACTATA 
               
               
                   
                   
                 GGAGTTAAAGAGTAAGTTGAGTGTAAGGTGGTAGAATTATGATTGAACTCCGAAACTAA 
               
               
                   
                   
                 GCGCCGATTATGGGTGGCAAAGCGGACAGCTTTTGATATATAATCGATCGCTCTCGTA 
               
               
                   
                   
                 GTTGATATCCTCTCTCTTGCTTATCTTTTCCTGTATATAGTATATGTGTACATACAGATAC 
               
               
                   
                   
                 GAATATACCTCAGTTAGTTTGTTTTAACATTAAATATTCAACAGTTGCCAGTAGCAAAAA 
               
               
                   
                   
                 GAATATATCCATTCATTTCGAGCTTTTTCGTCTCATTACTGATATCCAACTAACAGTCTC 
               
               
                   
                   
                 CTCATAGACGGTACCTTACTTTCCTTTAATATTATAATACTAGTATAGTCGCACATACTTA 
               
               
                   
                   
                 ACTCGTCTCTCTCTAACACATA 
               
               
                   
               
               
                 32 
                   S. cerevisiae  STL1 
                 CTACGTCGCCTGTTCGAGCGGCTCTGTTCGTTGCATGAAACTAAAATAAGCGGAAAGT 
               
               
                   
                   
                 GTCCAGCCATCCACTACGTCAGAAAGAAATAATGGTTGTACACTGTTTCTCGGCTATAT 
               
               
                   
                   
                 ACCGTTTTTGGTTGGTTAATCCTCGCCAGGTGCAGCTATTGCGCTTGGCTGCTTCGCG 
               
               
                   
                   
                 ATAGTAGTAATCTGAGAAAGTGCAGATCCCGGTAAGGGAAACACTTTTGGTTCACCTTT 
               
               
                   
                   
                 GATAGGGCTTTCATTGGGGCATTCGTAACAAAAAGGAAGTAGATAGAGAAATTGAGAAA 
               
               
                   
                   
                 GCTTAAGTGAGATGTTTTAGCTTCAATTTTGTCCCCTTCAACGCTGCTTGGCCTTAGAG 
               
               
                   
                   
                 GGTCAGAATTGCAGTTCAGGAGTAGTCACACTCATAGTATATAAACAAGCCCTTTATTG 
               
               
                   
                   
                 ATTTTGAATAATTATTTTGTATACGTGTTCTAGCATACAAGTTAGAATAAATAAAAAATAG 
               
               
                   
                   
                 AAAAATAGAACATAGAAAGTTTTAGACC 
               
               
                   
               
               
                 33 
                   S. cerevisiae  ALP1 
                 GAGCTATAGTCTTTTGCGCTTTCAATACGTGTAGCGGTGTACCAAAAGTTGCACAAAAA 
               
               
                   
                   
                 TGTAGTTGTCAATGAAAGCGCACTACGTATATAATGACTATTTTTTTTTTCCTGGGTTGC 
               
               
                   
                   
                 ATGGGTAATTTGTTGTTAATATGCGATTTTCTTGGGGAAAAGGGTGTCATAGCGCCAAA 
               
               
                   
                   
                 AACTGCCGTGCGGCACAGTATGTATGTTTTTGAGTCGCGGCGTTTAAGGGCTTGGCAT 
               
               
                   
                   
                 AAAAAGTGGTTCAAGCGAGTGATAAGTTGGGCGAATGTCGTCTTTTTTGTAACCATGTC 
               
               
                   
                   
                 TTTCCTGAAAACAACCTGTAGGCAGCTCCACTCCACATAAGGGCTTTCTCCAATGGCAA 
               
               
                   
                   
                 TGGGAGCTCGGAACACCGGAGTAGAAATTTTTATAATGTGTATTGTATAAAACTTGCTT 
               
               
                   
                   
                 GTTATGCAGTTTTTGTTTTTTTTGTTACTCTTCCGTAGCACAATAGACATATATTAGCGG 
               
               
                   
                   
                 CAAAATTGTAGTGTTGCGATTATTGCC 
               
               
                   
               
               
                 34 
                   S. cerevisiae  NDE2 
                 GTGTAGTATTGATCTTGTTGGTATTGCTAGAAATGCTTCAGCAATACTGTATAAAATATG 
               
               
                   
                   
                 GAAACGTTGCCATGGCAAGACAAAAGAAGTGATCTTGAGTGAAATAATAGAGCCCGGA 
               
               
                   
                   
                 TGGCCGGGTAAATTCAACCGCTCGTACCGTTTATAATACGCATAAACGCCGAAAATGTC 
               
               
                   
                   
                 TCTATTTTAGTCATTCCCCAGAGTGCGGTATTGCGTACACCTGTCATGCGTTCCTTAGT 
               
               
                   
                   
                 GCCGATAGATATACTAATATCGATGCGTCACAGTAGCAGATCATCTCTGACACTTGTTT 
               
               
                   
                   
                 CCCCATTTTTTTTTTTCATTTTTTAAAGGGTTTCTCTACAGCCTACAGGCCTCCCCTAATA 
               
               
                   
                   
                 AGTCAGCCCCTCCCTTTGGAGTGCGCTGTTGACCTGCGTATATAAGAGGTATATCAGT 
               
               
                   
                   
                 GCCAGTAGGTAAACCCATCTTGCGGGGATTGTACCAGGAACATAGTAGAAAGACAAAA 
               
               
                   
                   
                 ACAACCACCGTACTTGCCATTCGTATAG 
               
               
                   
               
               
                 35 
                   S. cerevisiae  QNQ1 
                 CATCAATTAGGGCAAACTTGAATAGTCAGCTAGGTCATATATTTAAAATCTTAGCCCT 
               
               
                   
                   
                 ATGACTACATTAGGTTTATTGTTAGGTCTTTACGGCTGCATATTTGCTTTCGCCGTTCGG 
               
               
                   
                   
                 CGGGGTCCTGCGACGATTTCTGCGCGGTCTTGTATGGGTGGAGTTGACAGTTAACCCT 
               
               
                   
                   
                 CCGGACCCCCTACCCCGGTGTGCCCCCGGTCCATCTATCCATTTTGCGGTAACCCCTT 
               
               
                   
                   
                 TGCGCGACAGCTGCTTATCAAGGTACCTGGATCGAGCCATAAAAATTGATCTACACAGA 
               
               
                   
                   
                 TGAGATGGGGCATTGGGATATATTATTAGTCGGAGTATCATTATAGTTATTCAGTTTTAT 
               
               
                   
                   
                 GCAGGTTACTGGCCAAACGTTTTTCTTCATTTGGAATAATCGTTTAGGAGCTACTGTTC 
               
               
                   
                   
                 CGGTATAAAGTAACAAGCACAGTAGCAGAGTAATACGCAGTGACGATAATAGAGACTA 
               
               
                   
                   
                 GTAAAACAGTCGAGTTGTCGGACCTAAA 
               
               
                   
               
               
                 36 
                   S. paradoxus  pADH2 
                 TAGTCTTATCTAAAAATTGCCTTTATAGTCCGTCTCTCCAGTCACGGCCTGTGTAACTGA 
               
               
                   
                   
                 TTAATCCTGCCTTTCTAATCACCATTCTACTGTTTAATTAAGGGATTTTGTCTTCATCAAC 
               
               
                   
                   
                 GGCTTCCGCCCAAAAAAAAGTATGACGTTTTGCCCGCAGGCGTGAAGCTGCCCATCTT 
               
               
                   
                   
                 CACGGGCCTGACCTCCTCTGCCGGAACACCGGCCATCTCCAACTCATAAATTGGAGAA 
               
               
                   
                   
                 ATAAGAGAATTTCAGATTTTCAGAGGATGAAAAAAAAAAGGTAGAGAGCATAAAAATGG 
               
               
                   
                   
                 GGTTCACTTTTTGGCAAAGTTACAGTATGCTTATTACATATAAATAGAGTGCCGATAATG 
               
               
                   
                   
                 GCTTTTTTTCATCTTCGAAATACGCTTGCTACTGCTCTTCCAGCGTTTTTATTACTTCTTT 
               
               
                   
                   
                 CTTGTTTCTCCTTAGTATATAAAATATCAAGCTACAACAAGCATACAATCAACTGTCAAC 
               
               
                   
                   
                 TGTCAATTATATTATAATACACT 
               
               
                   
               
               
                 37 
                   S. kudriavzevii  pADH2 
                 CTCTCAAATCTTTTAGCGCCAAGGACTCCAACTAATTGTATCTTGAATTTGCCTTTACGA 
               
               
                   
                   
                 TCCGTTTGTCCAGTCACGGCATGTATATCTTATTAATCCTGCCTTTCTAATCACGTATTC 
               
               
                   
                   
                 TAATGTTCAATTAAGGGATTTTATCTTCATCAACGGCTCCCACGCAAAAAATGACGTTTT 
               
               
                   
                   
                 GCACACAGACACGAAATACACCTTCCACCGGAACAACGGCCATCTCCAACTTATAAGTT 
               
               
                   
                   
                 GGGGAAATAAGACAATTTCAGACTTCAGAGAATGAAAAAAAAAAAAGGTACATCACAGA 
               
               
                   
                   
                 TGGGGTTCAGGTTTGCTACAATTGCAGGGAGCCTGTCACATATAAATAGACCTCCAGT 
               
               
                   
                   
                 GATGATATCTTTCAGTCTTCAAACGTCTCTTGTCACAGTTCTGGTCGTTCTATATCACAT 
               
               
                   
                   
                 CTCTCTTGGTTCTACTTATTGTCTATAATATCAAGCTACAGCAAGCATACAATCAACTAT 
               
               
                   
                   
                 CTACCATACCATAATACACA 
               
               
                   
               
               
                 38 
                   S. bayanus  pADH2 
                 GATCCAGTTCTCCAGTGACACAGCCTTTATCTGGTCAAACCTTTCTTTCTAATCACCTAT 
               
               
                   
                   
                 GCTGATGCTTAATTAAGGGATTTTTGTCTCCATCAACGGCATGCGCCCAAAAATGACGT 
               
               
                   
                   
                 TTTTTTTAACCCATAGACACGAAACTACCCATTTTCCACCGGCCTGACCTACCACCGGA 
               
               
                   
                   
                 ACAACGGCCATCTCCAACTTGCAAGTTGGGGAAATTAAGAGCATCGCAGGTTTAATGG 
               
               
                   
                   
                 AAGAAAAAAAAAAGGTACAGCACAGCGCAAATGGAGTTAGTTCCCTTATGTCACACACT 
               
               
                   
                   
                 CACACACAGTCGGTCAGATCAAGCATACTGGGTGCGTATAAATAGAGTGGCCATTGCC 
               
               
                   
                   
                 ACCCTGTTTATCTCAAAATCTGTCTTGTTAGTCTGTCTTCTCCCTTTTTCAGGTTACAATT 
               
               
                   
                   
                 CTCTTGTTTCTACTTAGTATATAAGTATATCAAGCTATATTAAGCATACTATCAACTGTCA 
               
               
                   
                   
                 ACTCTATCCTCAAAATACAATACAAA 
               
               
                   
               
               
                 39 
                   S. mikitae  pADH2 
                 TTTCCCAAAAAGTATTATTTTTAAGTGATAATTGATAAAAGGGGCAAAACGTAGACGCAA 
               
               
                   
                   
                 ATAAAACGGAAATAATGATTCTCAGACCTTTTAGCGTCAAGAACTGCAACTAATCTTATC 
               
               
                   
                   
                 TTAAAATTATCTTTATAATCCGTTTCTCCCGTCACAGTCTGTGTATCTGATTAATCCTGC 
               
               
                   
                   
                 CTTTCTAATCACCTATTCTAATGTTCAATTAAGGGATTTTGTCTTCACCAACGGCTTCCA 
               
               
                   
                   
                 CCCAAAAGTAAAAAATGACGTTGTACCCACAGACATCTTCACCGGCCTGACCTGCCAC 
               
               
                   
                   
                 CGGAACAACGGCCATCTCCAACTCATAAATTGGAGAAATAAGAGAATTTCAGATTCTGG 
               
               
                   
                   
                 AGGATGAAAAAAAAAAAGGTACAGCATAAATGGGGTTTTATGTGGGTACAATTACACTA 
               
               
                   
                   
                 GGACTATCACATATAAATAGACGGGCAATGTAGGTTCTTTTCCACCCTTGAGACAGAGT 
               
               
                   
                   
                 TATTC 
               
               
                   
               
               
                 40 
                   S. castellii  pADH2 
                 TGTCGTGGACGAAATACGCCACAATTTTGCCGAGAAGGTCATTAGTATGTCCAAGAAAC 
               
               
                   
                   
                 CCTAGGTGTAAAGTCGGGAAATCCGAATCTCCGATTTTGGAGGGGCCCATGCCCTACT 
               
               
                   
                   
                 TTTTTTCGCCAGGGGTGAAATTCCAAACCCGTGCGCGTTCTTGGAATTTGACAGCGCAT 
               
               
                   
                   
                 TGAGTATGTGCTGCGTATTCCCACTATCATGACGCGCCCTTTATCTGGGAAAAATGGAA 
               
               
                   
                   
                 CTGGATGCTGAAATATTTCACTCTCAGATCACATATCCCAAATCCIGTGAGTGAATTGTT 
               
               
                   
                   
                 TGGTCAGGCGACCAAACAGGAATATGGAATAGATTCTATTCTCTGGATTCTACAATTAT 
               
               
                   
                   
                 CCATTGTTAGCAAAACAAAAAAAACTGGTGGTATATATATTCAGAGCCTAAAATTTAAAG 
               
               
                   
                   
                 GTTGGATCTCAATTTTAAAAGTTTTCATTCTGTTTTGTTTTTGTTTCTTCTTAGCTCACGA 
               
               
                   
                   
                 ATAACCAAACAAAAAACAATCAATA 
               
               
                   
               
               
                 41 
                   S. paradoxus  pPCK1 
                 CAATAGGAAAAAACCAAGCTTCCTTTCATCCGGCACGGCTGTGTTGTACATATCACTGA 
               
               
                   
                   
                 AGCTCCGGGTATTTTAAGTTATACAAGAGAAATATGCGGGCTAGACTAGCAAGATTCTG 
               
               
                   
                   
                 GACTGTATAACGTTGTGGATAGGCGGATAAAGGGCCCAAACAGGATTGTAAAGCTTAG 
               
               
                   
                   
                 ACGCCTCTGGTTGGGCAATGGCATGTTTGTGTATTAAGTAAGACTTGGCTGCGGGATA 
               
               
                   
                   
                 GCAAAACTGAGCAGAATATAGAAGGCCACAAAAAAAAGGTATATAAGGGCAGCAAAGT 
               
               
                   
                   
                 CTTTATAATATATGTAGATTCTCTTCTCTGTGTAATTCATTCTTGTGCTTACCACTCAAAT 
               
               
                   
                   
                 ATACAGAAGTAAGACAGATAACCAACAGCCTTTCCCAGATATACATATATCTCATTGTTT 
               
               
                   
                   
                 CAGTTTAAACAATAATCATATTTGTTCTCAAAAATAAAAAAAAACTAAACTCACTCAA 
               
               
                   
                   
                 TCAATCATTCCATAAAAAAAAACAAT 
               
               
                   
               
               
                 42 
                   S. kudriavzevii  pPCK1 
                 CTTCCTTTCATCCGGCACGGCTGTGTCCCCACATCTCCCTAAAGCTCCGGGTATTTTAA 
               
               
                   
                   
                 GTTATACAAGGGAAATATACGGGCTGGACTACAACTTGCAGGTTGCACAGCGTTATGG 
               
               
                   
                   
                 ATAGGCGGATAAAGGGCCCAAGCAAGATCGTGAAGCTTGGACGCGTCTGGTTGGACA 
               
               
                   
                   
                 ATGGTGACTTTTTGTGTATTAGATAATGCTTGACTGGAGAATATCAGGACTGAGCAGAG 
               
               
                   
                   
                 TTAGGAAGACCACAAAAAAGGTATATAAGGGCAACGTCTCCGTGATATGGATAGG 
               
               
                   
                   
                 CTCTTCTCTCTGGTTACAATTCATTATTTCAGTTGTTFGCTAGATATAGAGATATAATACA 
               
               
                   
                   
                 TCTAATAAACAGTCACTTCCAGAGATATATATATATACATATATCTATCTCCTCCTCCCA 
               
               
                   
                   
                 GCTTAAATAATAACTATATTTGTTTAACTCGAAGAAAAAAAAAATTCAAATTTACTCTATC 
               
               
                   
                   
                 AATTCAATTACCTCATAAAAAACAATA 
               
               
                   
               
               
                 43 
                   S. bayanus  pPCK1 
                 CTTCCTTTCATCCGGCACGGCTGTGTCCCCACATCTCCCTAAAGCTCCGGGTATTTTAA 
               
               
                   
                   
                 GTTATACAAGGGAAATATACGGGCTGGACTACAACTTGCAGGTTGCACAGCGTTATGG 
               
               
                   
                   
                 ATAGGCGGATAAAGGGCCCAAGCAAGATCGTGAAGCTTGGACGCGTCTGGTTGGACA 
               
               
                   
                   
                 ATGGTGACTTTTTGTGTATTAGATAATGCTTGACTGGAGAATATCAGGACTGAGCAGAG 
               
               
                   
                   
                 TTAGGAAGACCACAAAAAAGGTATATAAGGGCAACAAAGTCTCCGTGATATGGATAGG 
               
               
                   
                   
                 CTCTTCTCTCTGGTTACAATTCATTATTTCAGTTGTTTGCTAGATATAGAGATATAATACA 
               
               
                   
                   
                 TCTAATAAACAGTCACTTCCAGAGATATATATATATACATATATCTATCTCCTCCTCCCA 
               
               
                   
                   
                 GCTTAAATAATAACTATATTTGTTTAACTCGAAGAAAAAAAAAATTCAAATTTACTCTATC 
               
               
                   
                   
                 AATTCAATTACCTCATAAAAAACAATA 
               
               
                   
               
               
                 44 
                   S. paradoxus  pMLS1 
                 CGATACCACACGGTCCATTGGGCCGGTGGTGTTAGTCGACGGATATATGCATCTGTCC 
               
               
                   
                   
                 CCTTTCCCGGCGAGCCGGCAGTCGGGCCGAGGTTCGGATAAATTTTTGCATTGTATTA 
               
               
                   
                   
                 GTTTCTGTCATGAGTATTACTTATGGTTCCTTTAGAGCTAATCATTAGCTCGGTACCGGC 
               
               
                   
                   
                 TGTTATGCAATTTATGACTTTTCTTCTACAGTGTCAGCCTTGTGACGATTATCTATGAAC 
               
               
                   
                   
                 TTTGGATGTAGCGCATCGAGATTCGTATCTTTCATTGGATAGTAAATGGGAAGGATCGA 
               
               
                   
                   
                 TGACCCTTATTACATTCTTTCCTATACTTAATATCCATTTAATCTATCTTCTTGAAAGTATA 
               
               
                   
                   
                 TAAGTAACGGTAAATTTACCATACTTATGCTATTCTCATTTATCCCCTAATTTTCTTTTAA 
               
               
                   
                   
                 CTTCTCGCCCTACAGTAACTAAGAATAACGGCTACTGTTTCGAAATTAAGCAAAGTAGT 
               
               
                   
                   
                 AAAGCACATAAAAGAATAAAGAA 
               
               
                   
               
               
                 45 
                   S. kudriavzevii  praS1 
                 AGACCGAAGCGGGTAATGGACGGAATTAAGCAATTGTCCCCTCTCCCGGGGAGCCGA 
               
               
                   
                   
                 CAGTCGGACCGAGCTTCGGATAAATTTCTGTATTGTTTFTGTTTCCGTCATGGGTATTAT 
               
               
                   
                   
                 TTTCGGGATCCTTTTGCCAACCCCATAGTCAATCGTTAACATTTACCGGCTATGTA 
               
               
                   
                   
                 GGATTATGACTATTCTCCTGCATGATCAGCGGAAGTGACGATTATCTATTAATTTTGAAC 
               
               
                   
                   
                 TTCTACTTCGTGATCCGGAATTTAATTGGATAATAATGTGTCCGAAGGATCGAGTGACC 
               
               
                   
                   
                 CTTATATTCTGTAGTTTTTTGTTACTGGCCATCCAATTCGTGTTCTTGGAAGTATATAAGT 
               
               
                   
                   
                 TACAGTCGATTGACCTTTCTCAAGCTATTTTCATCTTTCTCCTACATTTACGTTTCTCTTC 
               
               
                   
                   
                 TTCAATACAGCAGCTAGAAGTTACGATTACTCCTGTGATAAACAAAGTAATAGTAG 
               
               
                   
                   
                 CCCACAAAAAGAGAGAAAGTAAAA 
               
               
                   
               
               
                 46 
                   S. bayanus  pMLS1 
                 GTAGCAGTCCGGAAATAAGCAAATGTCCCCTTTCCCGAGCTAACCAACGGTCGGGCCG 
               
               
                   
                   
                 AGCCTCGGATAAATTTTTGCTTTGTTTTTGTTTCTGTCATGGGTATTATACATCATTTATT 
               
               
                   
                   
                 TAGTTAACCCCTAGACTAATTAGCCGGCCATTAGTATGTAAGATTATGACTATAGTTTGT 
               
               
                   
                   
                 ACCGGAACCCTGGTAGCAACTACTCATGAACTTTGGGCTCAGTATTTCGCAATCCCGG 
               
               
                   
                   
                 TTTTAATTGGATAGCCTATCGCGAAGGATCGATGGATGACCCTTAGAATTGTCTCTTTT 
               
               
                   
                   
                 GTTACTACTCATTCAATGCGTGTGCTCTTGCAAGTTATATAAGTCACTCTAAATTAGTTTA 
               
               
                   
                   
                 TACTTGAGCTTTTTACATTTCTCCCTTGATTGTTTCTTTCTCTTTTCCCCTTGTTCTGGTT 
               
               
                   
                   
                 TATTGTAATAGCTAAGTGCAACGATTACCGCTGTTAAGTTAAAGAAGAGAGACAAGTAA 
               
               
                   
                   
                 TAATAGTACACAGCAAGGAAAAAA 
               
               
                   
               
               
                 47 
                   S. paradoxus  pICL1 
                 TTACTAAATAGGCTGGCATCAGCTAACCCGGATGGTTGAATCCGGCTTTTGCTACTTGT 
               
               
                   
                   
                 TGTCCGATGAAAAGGAGCGGCTTCCCTTTTGCCCCAGATTTCCATTCATCCGAGAGGT 
               
               
                   
                   
                 CGCTTATCAGACTTCGTCATTTCTCATTTCATCCGAGATGATCAAAATTGAAGCCAATCA 
               
               
                   
                   
                 CCACAAAACTAACACTTAACGTCATGTTACACTACCOTTTACAGAAGAAAATATCCATAG 
               
               
                   
                   
                 TCCGGACTAACATTCCAGTATGTGACTCAATATTGGTGCAAATGAGAAAATCATAGCAG 
               
               
                   
                   
                 TCAGCCCAAGTCCGCCCTTTACCAGGGCACCGTAATTCACGAAACGTTTCTTTATTATA 
               
               
                   
                   
                 TAAAGGAGCTACTTTACTAGCAAAATTCTTGTAATTCCTCTTCCCTTGCTAACTTCTTCTT 
               
               
                   
                   
                 GTTTTCTTTTCCTTTTTACACACAGATATATAACAATTGAGAGAAAAACTCTAGTATAACA 
               
               
                   
                   
                 TAACAAAAAAGTCAACGAAAAAA 
               
               
                   
               
               
                 48 
                   S. kudriavzevii  pICL1 
                 GTTACGGTGCCGCGCCGGTGGCCGGTGGTCTTCCGGTAAACAAAAAAAGCTGCCTCC 
               
               
                   
                   
                 CTTTCGCCCCAGATTTCCATTCATCCGAGGGCACCGCTTGTCAGACTTTATCGTTTTCC 
               
               
                   
                   
                 TCATTTCATCCGAGAAGATCAATTCAAAGGCAATGACCACAAAAGCAACTCCTAACGTT 
               
               
                   
                   
                 GTGTTACGCTACCCTTTACACAAAATATTCATAACCCGTAATGAATCCTAAGGTATGTGA 
               
               
                   
                   
                 CTCAATTTTGGTGTAGAAAATGAGGAAAACGTAATACTAAGTTAAAGCTCGCCCTTTAAA 
               
               
                   
                   
                 GTGAATATTCCTTGACCATTTGCGCAGGCACACCCGAATTCACAAACGTTTCTTTATTAT 
               
               
                   
                   
                 ATAAAGGACCAGCTCTGCTAGTCAAATTTTTATAACTGCTTGTTCAGTTGCTGCTTCTTT 
               
               
                   
                   
                 CTTGTCAATTTATTTCTTGTACTGTTCAACTACATAAAGCAAAGAGAAAACTCTCAGAAT 
               
               
                   
                   
                 AACATAACAAAGAAGTCAACGAAAA 
               
               
                   
               
               
                 49 
                   S. bayanus  pICL1 
                 ACGAGGCTCGGCGTTTACTGCTGAATTTCCGGAAAGAAAGGGAAGGTTCCCTTTACCC 
               
               
                   
                   
                 CAGATTTCCATTCATCCGAAGGACTGCTTATCAGAATTTGACATTTTTCTCATTTTATCC 
               
               
                   
                   
                 GAGAAGATCAATTTAAGGCTAGTGACCACAAAACTAACTCTCATGCTGCGCTACCGCAA 
               
               
                   
                   
                 GTTTCGCTCACAGAAAGAAAGCAAGCACCCATAGTCCGGACTACATCCTTGTATGTGAC 
               
               
                   
                   
                 TCAAATTTTTGGCGTTGCCAATTAAACTGAAGTGTAAAGATTACTTCAAGCTCACCCTTT 
               
               
                   
                   
                 AAAGTAGAATTCCTTAACGGTTTTAAATAGACACACCGAAATTAATAAACACTTTCTTTAT 
               
               
                   
                   
                 TATATAAAGGACAGAGTTTATTACTGGAATTCTCTTAACGCCTTCCTCCCTTACTATTGT 
               
               
                   
                   
                 ATCTTTTCCTTTCACATAATCGCTACATAACTACATAGAGAAAACTCTCAGATTAACACA 
               
               
                   
                   
                 GTAACAACGAAGAAAACAAAAAA 
               
               
                   
               
               
                 50 
                   S. cerevisiae  pTDH3 
                 ACAGTTTATTCCTGGCATCCACTAAATATAATGGAGCCCGCTTTTTAAGCTGGCATCCA 
               
               
                   
                   
                 GAAAAAAAAAGAATCCCAGCACCAAAATATTGTTTTCTTCACCAACCATCAGTTCATAGG 
               
               
                   
                   
                 TCCATTCTCTTAGCGCAACTACAGAGAACAGGGGCACAAACAGGCAAAAAACGGGCAC 
               
               
                   
                   
                 AACCTCAATGGAGTGATGCAACCTGCCTGGAGTAAATGATGACACAAGGCAATTGACC 
               
               
                   
                   
                 CACGCATGTATCTATCTCATTTTCTTACACCTTCTATTACCTTCTGCTCTCTCTGATTTGG 
               
               
                   
                   
                 AAAAAGCTGAAAAAAAAGGTTGAAACCAGTTCCCTGAAATTATTCCCCTACTTGACTAAT 
               
               
                   
                   
                 AAGTATATAAAGACGGTAGGTATTGATTGTAATTCTGTAAATCTATTTCTTAAACTTCTTA 
               
               
                   
                   
                 AATTCTACTTTTATAGTTAGTCTTTTTTTTAGTTTTAAAACACCAAGAACTTAGTTTCGAAT 
               
               
                   
                   
                 AAACACACATAAACAAACAAA 
               
               
                   
               
               
                 51 
                   S. cerevisiae  pTEF1 
                 ATAGCTTCAAAATGTTTCTACTCCTTTTTTACTCTTCCAGATTTTCTCGGACTCCGCGCA 
               
               
                   
                   
                 TCGCCGTACCACTTCAAAACACCCAAGCACAGCATACTAAATTTCCCCTCTTTCTTCCT 
               
               
                   
                   
                 CTAGGGTGTCGTTAATTACCCGTACTAAAGGTTTGGAAAAGAAAAAAGAGACCGCCTC 
               
               
                   
                   
                 GTTTCTTTTTCTTCGTCGAAAAAGGCAATAAAAATTTTTATCACGTTTCTTTTTCTTGAAA 
               
               
                   
                   
                 ATTTTTTTTTTTGATTTTTTTCTCTTTCGATGACCTCCCATTGATATTTAAGTTAATAAACG 
               
               
                   
                   
                 GTCTTCAATTTCTCAAGTTTCAGTTTCATTTTTCTTGTTCTATTACAACTTTTTTTACTTCT 
               
               
                   
                   
                 TGCTCATTAGAAAGAAAGCATAGCAATCTAATCTAAGTTTTAATTACAAA 
               
               
                   
               
               
                 52 
                   S. cerevisiae  pFBA1 
                 TGGGTCATTACGTAAATAATGATAGGAATGGGATTCTTCTATTTTTCCTTTTTCCATTCTA 
               
               
                   
                   
                 GCAGCCGTCGGGAAAACGTGGCATCCTCTCTTTCGGGCTCAATTGGAGTCACGCTGCC 
               
               
                   
                   
                 GTGAGCATCCTCTCTTTCCATATCTAACAACTGAGCACGTAACCAATGGAAAAGCATGA 
               
               
                   
                   
                 GCTTAGCGTTGCTCCAAAAAAGTATTGGATGGTTAATACCATTTGTCTGTTCTCTTCTGA 
               
               
                   
                   
                 CTTTGACTCCTCAAAAAAAAAAAATCTACAATCAACAGATCGCTTCAATTACGCCCTCAC 
               
               
                   
                   
                 AAAAACTTTTTTCCTTCTTCTTCGCCCACGTTAAATTTTATCCCTCATGTTGTCTAACGGA 
               
               
                   
                   
                 TTTCTGCACTTGATTTATTATAAAAAGACAAAGACATAATACTTCTCTATCAATTTCAGTT 
               
               
                   
                   
                 ATTGTTCTTCCTTGCGTTATTCTTCTGTTCTTCTTTTTCTTTTGTCATATATAACCATAACC 
               
               
                   
                   
                 AAGTAATACATATTCAAA 
               
               
                   
               
               
                 53 
                   S. cerevisiae  pPDC1 
                 CATGCGACTGGGTGAGCATATGTTCCGCTGATGTGATGTGCAAGATAAACAAGCAAGG 
               
               
                   
                   
                 CAGAAACTAACTTCTTCTTCATGTAATAAACACACCCCGCGTTTATTTACCTATCTCTAA 
               
               
                   
                   
                 ACTTCAACACCTTATATCATAACTAATATTTCTTGAGATAAGCACACTGCACCCATACCT 
               
               
                   
                   
                 TCCTTAAAAACGTAGCTTCCAGTTTTTGGTGGTTCCGGCTTCCTTCCCGATTCCGCCCG 
               
               
                   
                   
                 CTAAACGCATATTTTTGTTGCCTGGTGGCATTTGCAAAATGCATAACCTATGCATTTAAA 
               
               
                   
                   
                 AGATTATGTATGCTCTTCTGACTTTTCGTGTGATGAGGCTCGTGGAAAAAATGAATAATT 
               
               
                   
                   
                 TATGAATTTGAGAACAATTTTGTGTTGTTACGGTATTTTACTATGGAATAATCAATCAATT 
               
               
                   
                   
                 GAGGATTTTATGCAAATATCGTTTGAATATTTTTCCGACCCTTTGAGTACTTTTCTTCATA 
               
               
                   
                   
                 ATTGCATAATATTGTCCGCTGCCCCTTTTTCTGTTAGACGGTGTCTTGATCTACTTGCTA 
               
               
                   
                   
                 TCGTTCAACACCACCTTATTTTCTAACTATTTTTTTTTTAGCTCATTTGAATCAGCTTATG 
               
               
                   
                   
                 GTGATGGCACATTTTTGCATAAACCTAGCTGTCCTCGTTGAACATAGGAAAAAAAAATAT 
               
               
                   
                   
                 ATAAACAAGGCTCTTTCACTCTCCTTGCAATCAGATTTGGGTTTGTTCCCTTTATTTTCA 
               
               
                   
                   
                 TATTTCTTGTCATATTCCTTTCTCAATTATTATTTTCTACTCATAACCTCACGCAAAATAA 
               
               
                   
                   
                 CACAGTCAAATCAATCAAA 
               
               
                   
               
               
                 54 
                   S. cerevisiae  pTPI1 
                 TATATCTAGGAACCCATCAGGTTGGTGGAAGATTACCCGTTCTAAGACTTTTCAGCTTC 
               
               
                   
                   
                 CTCTATTGATGTTACACCTGGACACCCCTTTTCTGGCATCCAGTTTTTAATCTTCAGTGG 
               
               
                   
                   
                 CATGTGAGATTCTCCGAAATTAATTAAAGCAATCACACAATTCTCTCGGATACCACCTC 
               
               
                   
                   
                 GGTTGAAACTGACAGGTGGTTTGTTACGCATGCTAATGCAAAGGAGCCTATATACCTTT 
               
               
                   
                   
                 GGCTCGGCTGCTGTAACAGGGAATATAAAGGGCAGCATAATTTAGGAGTTTAGTGAAC 
               
               
                   
                   
                 TTGCAACATTTACTATTTTCCCTTCTTACGTAAATATTTTTCTTTTTAATTCTAAATCAATC 
               
               
                   
                   
                 TTTTTCAATTTTTTGTTTGTATTCTTTTCTTGCTTAAATCTATAACTACAAAAAACACATAC 
               
               
                   
                   
                 ATAAACTAAAA 
               
               
                   
               
               
                 55 
                   S. cerevisiae  tADH2 
                 GCGGATCTOTTATGTCTTTACGATTTATAGTTTTCATTATCAAGTATGCCTATATTAGTAT 
               
               
                   
                   
                 ATAGCATCTTTAGATGACAGTGTTCGAAGTTTCACGAATAAAAGATAATATTCTACTTTTT 
               
               
                   
                   
                 GCTCCCACCGCGTTTGCTAGCACGAGTGAACACCATCCCTCGCCTGTGAGTTGTACCC 
               
               
                   
                   
                 ATTCCTCTAAACTGTAGACATGGTAGCTTCAGCAGTGTTCGTTATGTACGGCATCCTCC 
               
               
                   
                   
                 AACAAACAGTCGOTTATAGTTTGTCCTGCTCCTCTGAATCGTCTCCCTCGATATTTCTCA 
               
               
                   
                   
                 TTTTCCTTCGCATGCCAGCATTGAAATGATCGAAGTTCAATGATGAAACGGTAATTCTTC 
               
               
                   
                   
                 TGTCATTTACTCATCTCATCTCATCAAGTTATATAATTCTATACGGATGTAATTTTTCACT 
               
               
                   
                   
                 TTTCGTCTTGACGTCCACCCTATAATTTCAATTATTGAACCCTCAC 
               
               
                   
               
               
                 56 
                   S. cerevisiae  tPGI1 
                 ACAAATCGCTCTTAAATATATACCTAAAGAACATTAAAGCTATATTATAAGCAAAGATAC 
               
               
                   
                   
                 GTAAATTTTGCTTATATTATTATACACATATCATATTTCTATATTTTTAAGATTTGGTTATA 
               
               
                   
                   
                 TAATGTACGTAATGCAAAGGAAATAAATTTTATACATTATTGAACAGCGTCCAAGTAACT 
               
               
                   
                   
                 ACATTATGTGCACTAATAGTTTAGCGTCGTGAAGACTTTATTGTGTCGCGAAAAGTAAAA 
               
               
                   
                   
                 ATTTTAAAAATTAGAGCACCTTGAACTTGCGAAAAAGGTTCTCATCAACTGTTTAAAAGG 
               
               
                   
                   
                 AGGATATCAGGTCCTATTTCTGACAAACAATATACAAATTTAGTTTCAAAGATGAATCAG 
               
               
                   
                   
                 TGCGCGAAGGACATAACTCA 
               
               
                   
               
               
                 57 
                   S. cerevisiae  tENO2 
                 AGTGCTTTTAACTAAGAATTATTAGTCTTTTCTGCTTATTTTTTCATCATAGTTTAGCA 
               
               
                   
                   
                 CTTTATATTAACGAATAGTTTATGAATCTATTTAGGTTTAAAAATTGATACAGTTTTATAA 
               
               
                   
                   
                 GTTACTTTTTCAAAGACTCGTGCTGTCTATTGCATAATGCACTGGAAGGGGAAAAAAAA 
               
               
                   
                   
                 GGTGCACACGCGTGGCTTTTTCTTGAATTTGCAGTTTGAAAAATAACTACATGGATGAT 
               
               
                   
                   
                 AAGAAAACATGGAGTACAGTCACTTTGAGAACCTTCAATCAGCTGGTAACGTCTTCGTT 
               
               
                   
                   
                 AATTGGATACTCAAAAAAGATGGATAGCATGAATCACAAGATGGAAGGAAATGCGGGC 
               
               
                   
                   
                 CACGACCACAGTGATATGCATATGGGAGATGGAGATGATACCT 
               
               
                   
               
               
                 58 
                   S. cerevisiae  tTEF1 
                 GGAGATTGATAAGACTTTTCTAGTTGCATATCTTTTATATTTAAATCTTATCTATTAGTTA 
               
               
                   
                   
                 ATTTTTTGTAATTTATCCTTATATATAGTCTGGTTATTCTAAAATATCATTTCAGTATCTAA 
               
               
                   
                   
                 AAATTCCCCTCTTTTTTCAGTTATATCTTAACAGGCGACAGTCCAAATGTTGATTTATCC 
               
               
                   
                   
                 CAGTCCGATTCATCAGGGTTGTGAAGCATTTTGTCAATGGTCGAAATCACATCAGTAAT 
               
               
                   
                   
                 AGTGCCTCTTACTTGCCTCATAGAATTTCTTTCTCTTAACGTCACCGTTTGGTCTTTTAT 
               
               
                   
                   
                 AGTTTCGAAATCTATGGTGATACCAAATGGTGTTCCCAATTCATCGTTACGGGCGTATT 
               
               
                   
                   
                 TTTTACCAATTGAAGTATTGGAATCGTCAATTTTAAAGTATATCTCTCTTTTACGTAAAGC 
               
               
                   
                   
                 CTGCGAGATCCTCTTAAGTATAGCGGGGAAGCCATCGTTATTCGATATTGTCGTAACAA 
               
               
                   
                   
                 ATACTTTGATCGGCGCTAT 
               
               
                   
               
               
                 59 
                   A. tubingensis  GGPPS 
                 ATGCTGGGATTCCCAATGTTCAACCCAGCTACGCCTGATGTCTGGAAGATGAATACCC 
               
               
                   
                   
                 CTTACTTTCCATTTGTTACACCGGGGTTATTTCCTGCCTCAGCACCCCCATCGCCCACC 
               
               
                   
                   
                 AACGTAGATGCCGAAGCTGCCAGTTCCCAACAGTCGGAAGCAAGCTATCTGGATAAGG 
               
               
                   
                   
                 AGAAAATTGTTCGAGGGCCACTTGATTATCTTCTCAAATCCCCTGGAAAAGACATTCGT 
               
               
                   
                   
                 CGGAAATTCATTCACGCGTTCAATGAATGGCTGCGCATTCCTGAGGACAAGTTGAATAT 
               
               
                   
                   
                 TATCACGGAAATTGTTGGATTGCTTCACACGGCCTCCCTTCTAATCGACGATATTCAGG 
               
               
                   
                   
                 ACAATTCCAAGCTTCGACGCGGCCTCCCAGTGGCCCATAGCATATTTGGTATTGCGCA 
               
               
                   
                   
                 GACAATTAACTCTGCCAATTATGCGTACTTTCTAGCCCAGGAAAGGCTCCGCGAACTGA 
               
               
                   
                   
                 ATCATCCTGAAGCGTACGAAATATACACAGAGGAACTGCTTCGTCTGCACCGCGGTCA 
               
               
                   
                   
                 AGGTATGGACTTGTACTGGCGGGACTGCCTAACCTGTCCCACAGAGGAGGACTATATT 
               
               
                   
                   
                 GAGATGATCGCCAACAAGACTGGTGGCCTATTTCGACTGGCGATTAAGCTTATGCAGT 
               
               
                   
                   
                 TGGAAAGCACTTTGTGCAGCAATGTCATTGAACTAGCAGACTTGTTGGGCGTGATCTTT 
               
               
                   
                   
                 CAGATTCGGGATGATTACCAAAACTTACAGAGTGGACTATACGCCAAGAACAAGGGATT 
               
               
                   
                   
                 TTGCGAGGATTTGACGGAGGGAAAATTTTCCTTTCTGATTATCCACAGTATTAACAGTAA 
               
               
                   
                   
                 CCCGAACAATCACCATCTGCTAAATATACTACGGCAGCGGAGCGAGGACGATTCGGTG 
               
               
                   
                   
                 AAGAAGTATGCTGTTGATTATATCGACTCGACGGGGAGTTTTGACTACTGCCGGGAAC 
               
               
                   
                   
                 GGCTCGCTTCCTTATTGGAAGAGGCGGATCAAATGGTTAAGAAGTTGGAAAATGAGGG 
               
               
                   
                   
                 GGGACAATCAAAGGGGATCTACGATATTCTGAGCTTTCTGTCGTGA 
               
               
                   
               
               
                 60 
                   A. tubingensis  PT 
                 ATGGATGGGTTCGACCATTCTACIGCTCCACCAGGATATAACGAGCTAAAATGGCTCG 
               
               
                   
                   
                 CCGATATCTTCGTCATCGGAATGGCTGTTGGCTGGGTTGCTCACTATATGGAGATGATT 
               
               
                   
                   
                 CACACGTCGTTCAAGGACCAAACATACTGCATGACCATCGGGGGCCTTTGCATCAATTT 
               
               
                   
                   
                 TGCCTGGGAAATCATATTCTGCACAATGTATCCTGCCAAAGGATTTGTCGAGCGGGTTG 
               
               
                   
                   
                 CCTTTCTCATGGGCATTTCTCTCGACCTTGGGGTTATTTACGCGGGAATCAAGAACGCC 
               
               
                   
                   
                 CCAAATGAATGGCACCACTCTGCAATGGTGAGGGACCATATGCCCCTTGTCTTCGCAG 
               
               
                   
                   
                 CAACGACACTTTGTTGTCTGAGCGGTCATATGGCTCTTACTGCCCAGGTTGGTCCCGC 
               
               
                   
                   
                 ACAAGCCTATACGTGGGGGGCAATTGCATGCCAGCTCTTTATCAGCATAGGGAATGTG 
               
               
                   
                   
                 TTTCAATTGTTGAGTCGGGGAAACACACGAGGGGCGTCATGGACGCTATGGACCTCCA 
               
               
                   
                   
                 GGTTTTTTGGATCAACATCAGCCATTGGCTTTGCTCTTGTTCGATATATTCGCTGGTGG 
               
               
                   
                   
                 GAGGCCTTTTCTTGGTTGAACTGCCCGCTTGTGATATGGTCCGTGGCCATGTTCTTTCT 
               
               
                   
                   
                 GTTTGAAACACTCTATGGAGCCCTATTCTATTCTGTCAAGCGACAAGAAGGGAGATCCC 
               
               
                   
                   
                 AGCGTGGAATCAAGCACAAAGAGAGGTAG 
               
               
                   
               
               
                 61 
                   A. tubingensis  FMO 
                 ATGGCGGCACTTCCGGACGTTGCCTCCATTCCCATCCCTCTGGTGGCAACCCTAGGCA 
               
               
                   
                   
                 TTGCCCCTCTAATTTTCTATCTCGTCCTTGATAGAATTAGCCCCTTGTGGCCAAATTCCA 
               
               
                   
                   
                 AAGCTTTCCTGATTGGCAAGAAGACCGGAGACCGTGACATCGTTCGAGTGCCCATA 
               
               
                   
                   
                 TGCCTACATCCGTCAGATCTATGGGAAGTATCACTGGGAGCCATTCGTACAGAAGCTG 
               
               
                   
                   
                 TCTCCGAGGCTTAAGGATGAGGATCCGGCCAAATATAAGATGGTTCTGGAGATAATGG 
               
               
                   
                   
                 ATGCAATCCACCTGTGTCTGATGCTAGTTGACGATATAACTGACAATAGCGACTATCGA 
               
               
                   
                   
                 AAAGGCAAGCCAGCAGCCCACCGGATATATGGCCCTTCAGAGACAGCAAATCGCGCTT 
               
               
                   
                   
                 ACTACCGAGTCACCCAGATTCTAAACAAGACCGTGCAAAAGTTCCCCAAGCTGGCCAA 
               
               
                   
                   
                 GTTCCTGCTTCAGAATCTGGAAGAAATTCTCGAAGGCCAAGACCTGTCACTAATCTGGC 
               
               
                   
                   
                 GACGGGATGGACTGGGTAGCCTTTCGACTGTTCCTGATGAGCGAGTTGCAGCCTATCG 
               
               
                   
                   
                 CAAGATGGCGTCATTGAAAACTGGGGCGTTATTCCGGCTGCTGGGGCAATTGGTGATG 
               
               
                   
                   
                 GAGGACCAATCGATGGACGGGACGATGACTACTCTTGCGTGGTGCTCTCAGCTGCAG 
               
               
                   
                   
                 AATGACTGCAAGAATGTCTACTCATCTGAATATGCTAAGGCCAAAGGGGCGCTTGCCG 
               
               
                   
                   
                 AAGACCTCCGAAATCGAGAGCTCTCATTTCCAATTATCCTCGCGCTGGAAGCTCCTGAA 
               
               
                   
                   
                 GGGCATTGGGTCGCCAGTGCTTTGGAGACCAGCTCACCGCGCAACATTCGCAAGGCG 
               
               
                   
                   
                 CTTGCTGTGATTCAGAGTGAGAGAGTGCGCAATGCTTGTTTCAAGGAGCTCAAGTCGG 
               
               
                   
                   
                 CGAGTGCTTCGGTCCAGGACTGGTTGGCTATTTGGGGACGGAACGAGAAAATGAACTT 
               
               
                   
                   
                 GAAGAGCCAGCAGACGTAG 
               
               
                   
               
               
                 62 
                   A. tubingensis  Cyc 
                 ATGGCCAATGCCCAGCAACCCCCCTTTCGCATCCTTATTGTGGGCGGTTCTGTCGCAG 
               
               
                   
                   
                 GCCTCATCCTTGCGCACTGTCTCGAACGCGCCAATATAGAGTACCTCATACTCGAAAAA 
               
               
                   
                   
                 GGAGAAGATGTTGCTCCACAAGTTGGTGCCTCGATAGGTATCATGCCAAATGGCGGAC 
               
               
                   
                   
                 GGATCCTCGAGCAACTGGGCCTATTTGGGGAGATTGAGCGTGTGATCGAGCCGTTGC 
               
               
                   
                   
                 ATCAGGCGAATATCAGCTATCCAGATGGGTTCTGCTTTAGTAACGTCTATCCTAAGGTT 
               
               
                   
                   
                 CTTGGCGACAGGTTCGGATACCCGGTTGCATTCTTGGACCGGCAGAAGTTCCTGCAGA 
               
               
                   
                   
                 TTGCATATGAGGGGCTGAGAAAGAAGCAGAATGTTCTCACCGGTAAAAGGGTAGTTGG 
               
               
                   
                   
                 ACTGCGACAGTCGGATCAAGGGACTGCTGTTTCTGTGGCTGACGGGACAGAGTATGA 
               
               
                   
                   
                 GGCGGATCTCGTGGTTGGTGCTGATGGAGTACATAGTCGGGTGAGAAGTGAGATTTG 
               
               
                   
                   
                 GAAGATGGCGGAAGAGAATCAGCCTGCATCAGTTTCGACACGTGAAAGAAGAAGCATG 
               
               
                   
                   
                 ACTGTTGAATATGTCTGCGTTTTCGGGATTTCATCAGCCATCCCAGGGCTCGAGATAAG 
               
               
                   
                   
                 CGAACAGATCAACGGTATTTTCGACCATCTATCCATTCTAACAATCCATGGCAGACATG 
               
               
                   
                   
                 GTCGCGTGTTCTGGTTCGTGATCCAGAAGCTGGATAGGAAGTACGTCTATCCTGATGT 
               
               
                   
                   
                 CCCGCGATTCTCAGACGAGGATGCCGTACAGCTCTTCGATCGGGTCAAACACGTGCG 
               
               
                   
                   
                 GTTCTGGAAAAACATCTGTGTGGGGGACTTGTGGAAGAACAGAGAGGTGTCCTCGATG 
               
               
                   
                   
                 ACAGCGCTGGAGGAGGGAGTGTTCGAGACATGGCATCATGATAGGATGGTTTTGATTG 
               
               
                   
                   
                 GAGATAGCGTTCACAAGATGACGCCCAACTTTGGCCAAGGAGCTAATTCAGCCATCGA 
               
               
                   
                   
                 GGATGCTGCCGCGCTCTCTTCCCTTCTACATGATCTCGTCAACGCCCGTGGAGTTTGC 
               
               
                   
                   
                 AAGCCATCGAATGTCCAGATTCAGCATCTCCTCAAGCAGTATCGGGAGACCCGATACA 
               
               
                   
                   
                 CTCGCATGGTAGGCATGTGTCGCACCGCGGCTTCAGTCTCTCGGATTCAGGCCCGAG 
               
               
                   
                   
                 ATGGCATCCTCAACACCGTCTTTGGACGATATTGGGCACCTTATGCTGGCAACCTGCC 
               
               
                   
                   
                 TGCTGACCTGGCATCAAAAGTGATGGCAGATGCAGAGGTTGTTACTTTTCTGCCCTTGC 
               
               
                   
                   
                 CAGGGCGCTCAGGACCGGGCTGGGAGATGTACAGACGAAAGGGGAAGGGAGGGCAG 
               
               
                   
                   
                 GTGCAATGGGTGCTTATAATCTTAAGCTTACTTACGATTGGTGGATTGTGCATCTGGCT 
               
               
                   
                   
                 ACAAAGCAATGCGTTGAGTAGATAA 
               
               
                   
               
               
                 63 
                   H. subiculosis  hpm8 
                 ATGCCTTCTACCAGCAATCCATCTCACGTCCCTGTGGCCATCATCGGCCTGGCATGCC 
               
               
                   
                   
                 GATTCCCAGGCGAGGCCACCTCACCATCAAAATTCTGGGATCTTCTTAAGAATGGACG 
               
               
                   
                   
                 AGATGCCTACTCACCAAATACCGATCGATATAACGCTGATGCCTTTTACCATCCCAAGG 
               
               
                   
                   
                 CAAGCAACCGCCAAAACGTGCTGGCAACTAAGGGCGGCCACTTCCTCAAACAGGACC 
               
               
                   
                   
                 CATACGTTTTTGACGCCGCTTTCTTTAACATCACAGCCGCTGAGGCCATCTCCTTTGAC 
               
               
                   
                   
                 CCCAAGCAGCGAATTGCCATGGAAGTTGTCTACGAGGCTCTAGAAAATGCCGGAAAGA 
               
               
                   
                   
                 CACTACCCAAGGTGGCGGGCACACAAACTGCTTGCTATATCGGCTCTTCCATGAGTGA 
               
               
                   
                   
                 TTACCGAGACGCTGTTGTGCGTGACTTTGGAAACAGCCCCAAGTATCATATCCTGGGA 
               
               
                   
                   
                 ACATGCGAGGAGATGATTTCAAATCGTGTGTCCCATTTCTTGGATATTCACGGCCCCAG 
               
               
                   
                   
                 TGCCACCATTCATACAGCCTGCTCATCAAGTCTTGTTGCTACACACTTGGCTTGCCAAA 
               
               
                   
                   
                 GTTTGCAATCTGGAGAGTCAGAAATGGCCATCGCTGGTGGTGTTGGTATGATCATCAC 
               
               
                   
                   
                 CCCTGATGGTAATATGCATCTTACAACTTGGGATTCTTGAACCCCGAGGGCCACTCCC 
               
               
                   
                   
                 GGTCATTTGATGAGAATGCTGGTGGTTACGGTCGTGGTGAGGGTTGCGGTATCCTCAT 
               
               
                   
                   
                 CCTCAAGCGGCTAGACAGAGCTCTCGAAGATGGTGATTCCATTCGCGCCGTCATTCGA 
               
               
                   
                   
                 GCCTCTGGTGTCAACTCTGATGGCTGGACACAGGGTGTCACCATGCCCTCCAGCCAAG 
               
               
                   
                   
                 CCCAGTCTGCCCTTATCAAATACGTATACGAATCGCATGGCCTGGATTATGGTGCGACT 
               
               
                   
                   
                 CAATACGTTGAGGCTCACGGTACTGGTACCAAAGCCGGTGATCCCGCAGAGATTGGC 
               
               
                   
                   
                 GCCCTCCACCGCACAATTGGACAGGGCGCGTCCAAGTCTCGAAGGCTTTGGATTGGC 
               
               
                   
                   
                 AGTGTCAAGCCAAACATTGGCCATCTTGAAGCCGCCGCCGGTGTGGCTGGTATCATTA 
               
               
                   
                   
                 AGGGCGTCCTGTCCATGGAACACGGCATGATTCCTCCAAACATTTACTTCTCCAAGCC 
               
               
                   
                   
                 CAACCCTGCCATCCCTCTTGACGAGTGGAACATGGCCGTGCCTACCAAGTTGACTCCC 
               
               
                   
                   
                 TGGCCCGCCAGCCAAACTGGTCGCCGTATGAGTGTCAGCGGTTTCGGTATGGGTGGT 
               
               
                   
                   
                 ACCAACGGCCACGTCGTCCTTGAGGCCTACAAGCCCCAAGGAAAGCTCACCAACGGC 
               
               
                   
                   
                 CATACCAACGGCATCACCAATGGAATCCACAAGACTCGCCACAGCGGCAAGAGGCTTT 
               
               
                   
                   
                 TCGTCCTCAGCGCCCAGGATCAAGCTGGCTTCAAGCGTTTGGGTAACGCCCTGGTGG 
               
               
                   
                   
                 AGCATCTCGATGCCCTGGGCCCTGCCGCTGCCACCCCTGAGTTCCTCGCCAACCTCTC 
               
               
                   
                   
                 CCACACTCTTGCCGTTGGCAGATCTGGCTTGGCTTGGAGGTCCAGCATCATCGCTGAG 
               
               
                   
                   
                 AGCGCCCCTGATCTTCGGGAGAAGCTGGCAACTGATCCGGGTGAGGGAGCCGCTCGT 
               
               
                   
                   
                 TCTTCAGGCAGCGAGCCCCGTATTGGATTCGTCTTCACGGGTCAAGGTGCTCAGTGGG 
               
               
                   
                   
                 CCCGCATGGGCGTTGAGTTGTTGGAGCGCCCCGTCTTCAAGGCTTCCGTGATTAAGTC 
               
               
                   
                   
                 CGCGGAGACTTTGAAGGAGCTCGGCTGTGAATGGGACCCTATCGTTGAGCTTTCCAAG 
               
               
                   
                   
                 CCTCAAGCTGAGTCTCGACTTGGTGTTCCTGAAATCTCACAGCCCATCTGCACAGTCCT 
               
               
                   
                   
                 ACAAGTCGCCTTGGTTGATGAGTTGAAGCACTGGGGTGTATCACCTTCCAAGGTGGTC 
               
               
                   
                   
                 GGTCACTCCAGTGGTGAAATCGGTGCCGCATACAGCATTGGCGCTCTTTCTCACCGTG 
               
               
                   
                   
                 ACGCTGTCGCCGCTGCTTACTTCAGGGGCAAGTCTTCCAACGGAGCCAAGAAGCTTGG 
               
               
                   
                   
                 TGGTGGTATGATGGCTGTTGGGTGCTCTCGTGAGGACGCTGACAAGCTCCTCTCTGAG 
               
               
                   
                   
                 ACCAAGCTCAAGGGCGGTGTTGCTACCGTCGCATGTGTCAACTCCCCCTCCAGCGTGA 
               
               
                   
                   
                 CCATCTCAGGCGATGCCACTGCTCTCGAGGAACTCCGAGTTATTCTCGAGGAGAAGAG 
               
               
                   
                   
                 TGTGTTTGCTCGAAGACTCAAGGTCGACGTTGCCTACCACTCTGCCCACATGAACGCT 
               
               
                   
                   
                 GTCTTTGCCGAATACTCTGCTGCGATTGCCCACATTGAGCCCGCTCAGGCAGTTGAAG 
               
               
                   
                   
                 GTGGACCGATTATGGTCTCCAGTGTCACTGGTAGCGAAGTCGACTCTGAGCTTCTCGG 
               
               
                   
                   
                 CCCTTACTACTGGACCCGTAACTTGATCTCTCCCGTCTTATTCGCCGACGCTGTCAAGG 
               
               
                   
                   
                 AATTGGTTACCCCTGCTGATGGCGACGGCCAAAACACCGTCGATCTCCTGATTGAGAT 
               
               
                   
                   
                 TGGTCCTCACAGCGCTCTTGGTGGCCCTGTTGAGCAGATTCTGTCCCATAACGGCATC 
               
               
                   
                   
                 AAGAATGTTGCTTACAGATCTGCTCTTACTCGTGGCGAGAACGCTGTTGACTGCAGCCT 
               
               
                   
                   
                 CAAGCTTGCTGGCGAGCTCTTCCTTCTCGGCGTGCCCTTTGAGTTGCAAAAGGCCAAC 
               
               
                   
                   
                 GGTGACTCTGGTTCTCGCATGCTCACTAACCTACCTCCTTATCCTTGGAACCACTCCAA 
               
               
                   
                   
                 GTCATTCCGTGCCGACTCTCGTCTCCACCGTGAGCATCTGGAGCAGAAATTCCCTACT 
               
               
                   
                   
                 AGGAGTCTCATCGGTGCACCTGTCCCCATGATGGCAGAGAGCGAGTACACATGGCGC 
               
               
                   
                   
                 AACTTCATCCGTCTCGCTGACGAGCCTTGGCTCCGTGGTCACACTGTCGGTACCACCG 
               
               
                   
                   
                 TTCTGTTTCCTGGTGCCGGTATCGTGAGCATCATCTTGGAAGCTGCTCAACAGCTGGT 
               
               
                   
                   
                 GGATACCGGCAAGACCGTTCGGGGCTTCCGAATGCGCGATGTCAACCTCTTCGCCGC 
               
               
                   
                   
                 CATGGCTCTCCCCGAGGACCTGGCTACTGAGGTTATCATCCACATCCGACCTCACCTT 
               
               
                   
                   
                 ATCTCTACTGTTGGATCAACCGCCCCCGGTGGATGGTGGGAGTGGACTGTTTCCTCCT 
               
               
                   
                   
                 GCGTCGGAACTGACCAGCTGCGAGACAATGCTCGCGGTCTGGTAGCCATTGACTACG 
               
               
                   
                   
                 AAGAGAGCCGCAGCGAGCAGATCAACGCCGAGGACAAAGCGTTGGTTGCTTCTCAGG 
               
               
                   
                   
                 TCGCGGACTACCACAAGATCCTCAGCGAATGCCCTGAGCATTATGCTCATGACAAGTT 
               
               
                   
                   
                 CTACCAGCACATGACCAAGGCCTCTTGGAGCTACGGCGAGCTCTTCCAGGGTGTGGA 
               
               
                   
                   
                 GAATGTCCGTCCTGGATACGGAAAGACCATCTTTGACATCAGAGTCATTGACATTGGTG 
               
               
                   
                   
                 AGACCTTTAGCAAGGGACAACTTGAGCGACCTTTCCTCATCAACGCTGCCACTCTCGAT 
               
               
                   
                   
                 GCTGTATTCCAGAGCTGGCTCGGCAGTACCTACAACAACGGTGCTTTCGAGTTTGACA 
               
               
                   
                   
                 AGCCCTTCGTTCCCACCTCTATTGGCGAGTTGGAAATCTCTGTCAACATTCCCGGTGAT 
               
               
                   
                   
                 GGCGACTACCTCATGCCAGGCCACTGCCGCTCTGAGCGATACGGCTTCAACGAGTTGT 
               
               
                   
                   
                 CTGCTGATATTGCCATCTTCGACAAGGATCTGAAGAATGTGTTCCTTTCAGTGAAGGAT 
               
               
                   
                   
                 TTCCGAACTTCCGAGCTTGATATGGATTCCGGCAAGGGAGACGGAGATGCCGCTCACG 
               
               
                   
                   
                 TCGACCCTGCCGATATCAACTCGGAGGTTAAGTGGAACTACGCTCTTGGCCTCCTCAA 
               
               
                   
                   
                 GTCCGAGGAAATCACCGAGCTGGTCACCAAGGTCGCCAGCAATGACAAGCTCGCCGA 
               
               
                   
                   
                 GCTTCTCCGTCTGACACTTCACAACAACCCTGCTGCCACTGTCATCGAGCTTGTTTCTG 
               
               
                   
                   
                 ATGAGAGCAAGATCTCTGGCGCATCTTCTGCCAAGCTGTCCAAGGGCCTTATCCTCCC 
               
               
                   
                   
                 CAGCCAGATCCGTTACGTAGTTGTCAACCCTGAGGCAGCGGACGCCGACTCTTTCTTC 
               
               
                   
                   
                 AAATTCTTCTCCCTTGGTGAGGATGGTGCCCCTGTCGCTGCTGAAAGGGGCCCCGCC 
               
               
                   
                   
                 GAACTGTTGATCGCCTCCAGCGAAGTCACTGACGCGGCTGTCCTTGAGCGCCTGATTA 
               
               
                   
                   
                 CCTTGGCCAAGCCTGATGCCAGCATTCTTGTTGCTGTCAACAACAAGACTACCGCCGC 
               
               
                   
                   
                 TGCCCTCTCAGCCAAGGCGTTCCGTGTTGTCACCAGCATCCAGGACAGCAAGTCCATT 
               
               
                   
                   
                 GCTCTCTACACTAGCAAGAAGGCGCCTGCCGCCGACACCTCCAAGCTCGAGGCCATC 
               
               
                   
                   
                 ATCCTCAAGCCAACCACTGCTCAACCTGCCGCCCAGAATTTCGCCTCCATCCTCCAGA 
               
               
                   
                   
                 AGGCACTCGAGCTCCAGGGCTACTCTGTCGTTTCTCAGCCATGGGGCACCGACATCGA 
               
               
                   
                   
                 CGTCAACGATGCCAAGGGAAAGACCTACATTTCTCTGTTGGAGCTTGAGCAGCCTCTG 
               
               
                   
                   
                 CTCGACAACCTCTCCAAGTCCGACTTCGAGAACCTCCGCGCAGTCGTTTTGAACTGCG 
               
               
                   
                   
                 AGCGTCTCCTGTGGGTCACAGCAGGTGACAACCCATCTTTCGGCATGGTTGATGGTTT 
               
               
                   
                   
                 CGCTCGCTGCATCATGAGCGAAATTGCCAGCACCAAGTTCCAGGTCCTGCATTTGAGC 
               
               
                   
                   
                 GCTGCAACTGGTCTGAAGTACGGATCTTCTCTCGCCACCCGCATTCTCCAGTCGGATA 
               
               
                   
                   
                 GCACCGACAACGAGTACCGGGAGGTCGATGGTGCTCTCCAGGTGGCCCGTATCTTCA 
               
               
                   
                   
                 AGAGCTACAACGAGAACGAGAGTCTCCGCCACCACCTCGAGGATACCACCAGCGTTGT 
               
               
                   
                   
                 GACTCTTGCTGACCAGGAGGATGCTCTGCGCCTCACTATTGGCAAGCCTGGTCTTTTG 
               
               
                   
                   
                 GATACTTTGAAGTTTGTCCCCGATGAGCGTATGCTCCCACCTCTCCAGGATCACGAGG 
               
               
                   
                   
                 TTGAAATCCAGGTCAAGGCTACTGGTCTGAACTTCCGAGACATCATGGCTTGCATGGG 
               
               
                   
                   
                 TCTTATTCCTGTTCGATCTCTGGGCCAGGAGGCCAGTGGCATCGTCCTCAGAACCGGT 
               
               
                   
                   
                 GCGAAGGCTACCAACTTCAAGCCTGGCGACCGTGTTTGCACCATGAACGTCGGAACAC 
               
               
                   
                   
                 ATGCCACCAAGATCCGAGCCGACTACCGTGTCATGACAAAGATCCCCGACTCCATGAC 
               
               
                   
                   
                 CTTTGAAGAAGCTGCCTCGGTTGCTGTTGTTCACACCACCGCCTACTACGCCTTCATCA 
               
               
                   
                   
                 CCATCGCCAAGCTTCGCAAGGGCCAGTCCGTCTTGATCCACGCCGCCGCTGGTGGTG 
               
               
                   
                   
                 TTGGCCAAGCAGCCATTCAGTTGGCCAAGCATCTCGGCCTCATCACCTATGTTACCGT 
               
               
                   
                   
                 AGGTACTGAAGACAAGCGCCAGCTCATTCGGGAGCAGTATGGCATTCCCGACGAGCA 
               
               
                   
                   
                 CATCTTCAACTCCCGTGATGCCAGCTTCGTCAAGGGTGTCCAGCGTGTTACCAACGGT 
               
               
                   
                   
                 CGCGGTGTCGACTGCGTTCTCAACTCTCTATCCGGTGAGCTCCTGCGTGCTTCTTGGG 
               
               
                   
                   
                 GATGCCTTGCTACCTTTGGTCATTTCATCGAAATTGGTCTCCGTGATATCACCAACAAC 
               
               
                   
                   
                 ATGCGTCTTGACATGCGACCTTTCCGCAAGAGCACCTCCTTCACATTCATCAACACCCA 
               
               
                   
                   
                 CACTCTCTTCGAGGAAGACCCCGCTGCGTTGGGAGATATTCTCAACGAGTCCTTCAAG 
               
               
                   
                   
                 CTCATGTTCGCTGGCGCCCTTACCGCTCCTAGCCCCTTGAATGCCTATCCCATTGGCC 
               
               
                   
                   
                 AGGTCGAGGAGGCCTTCCGAACCATGCAGCAGGGCAAGCACCGCGGTAAGATGGTGC 
               
               
                   
                   
                 TGTCCTTCTCCGATGACGCAAAGGCTCCCGTGTTGCGCAAAGCGAAGGATTCCTTGAA 
               
               
                   
                   
                 ACTGGACCCTGACGCCACTTACCTCTTTGTTGGTGGTCTTGGTGGTCTGGGTCGCAGT 
               
               
                   
                   
                 CTTGCCAAGGAGTTTGTTGCGTCTGGCGCCCGCAACATTGCCTTCTTATCCCGATCCG 
               
               
                   
                   
                 GTGACACTACCGCCCAGGCCAAGGCTATCGTGGACGAATTGGCTGGCCAGGGTATCC 
               
               
                   
                   
                 AGGTCAAGGCCTATCGTGGTGATATCGCCAGCGAGGCATCCTTCCTCCAGGCTATGGA 
               
               
                   
                   
                 GCAATGCTCTCAGGATCTCCCGCCCGTAAAGGGTGTGATCCAGATGGCCATGGTTCTC 
               
               
                   
                   
                 CGCGATATCGTCTTTGAGAAGATGTCGTACGATGAGTGGACCGTCCCCGTTGGCCCCA 
               
               
                   
                   
                 AGGTCCAAGGTTCATGGAACTTGCACAAGTACTTCAGTCATGAGCGACCTCTTGACTTC 
               
               
                   
                   
                 ATGGTCATCTGCTCCTCAAGCTCCGGTATCTACGGTTATCCCAGTCAGGCTCAATACGC 
               
               
                   
                   
                 CGCTGGCAACACTTACCAGGATGCCTTGGCTCACTACCGTCGCTCTCAGGGCCTGAAC 
               
               
                   
                   
                 GCCATCTCCGTCAACTTGGGTATCATGCGAGATGTCGGTGTCCTGGCTGAGACGGGTA 
               
               
                   
                   
                 CCACTGGTAACATCAAGCTCTGGGAAGAGGTCTTGGGCATCCGCGAGCCTGCCTTCCA 
               
               
                   
                   
                 CGCTCTCATGAAGAGCTTGATCAACCATCAGCAGCGTGGGTCTGGGGACTACCCGGC 
               
               
                   
                   
                 GCAGGTCTGCACTGGTCTTGGTACTGCTGACATTATGGCTACTCACGGCCTGGCCCGG 
               
               
                   
                   
                 CCCGAGTATTTCAATGACCCCCGTTTTGGACCCCTTGCCGTCACCACTGTCGCGACCG 
               
               
                   
                   
                 ATGCTTCAGCTGACGGCCAGGGCTCTGCTGTCTCGCTCGCCTCTAGGCTCTCCAAGGT 
               
               
                   
                   
                 TTCCACCAAGGATGAAGCTGCCGAGATCATTACCGATGCTCTGGTCAACAAGACGGCA 
               
               
                   
                   
                 GACATCCTGCAGATGCCCCCCTCTGAAGTCGACCCCGGCCGACCTCTGTACCGTTATG 
               
               
                   
                   
                 GTGTTGACTCCCTTGTGGCGCTTGAGGTGCGAAACTGGATCACAAGGGAGATGAAGG 
               
               
                   
                   
                 CGAACATGGCGCTGCTGGAGATTCTGGCAGCCGTCCCCATTGAGAGCTTCGCTGTCAA 
               
               
                   
                   
                 GATTGCTGAGAAGAGCAAGTTGGTTACTGTTTAA 
               
               
                   
               
               
                 64 
                   H. subiculosis  hpm3 
                 ATGGTGACTGTACCACAGACTATCCTCTACTTTGGAGATCAGACAGACTCCTGGGTTGA 
               
               
                   
                   
                 TTCCCTCGATCAGCTATACAGACAAGCCGCTACGATACCATGGCTACAGACGTTTCTCG 
               
               
                   
                   
                 ACGACCTTGTAAAGGTCTTCAAGGAAGAGTCCCGGGGCATGGATCATGCGTTACAAGA 
               
               
                   
                   
                 CAGTGTTGGTGAATACTCTACACTACTCGACTTGGCGGATAGATACCGCCATGGCACC 
               
               
                   
                   
                 GACGAGATTGGTATGGTGCGTGCTGTCTTGCTACATGCCGCGAGAGGAGGCATGCTAT 
               
               
                   
                   
                 TACAATGGGTGAAGAAAGAATCACAGCTTGTGGACCTCAATGGCTCCAAGCCTGAAGC 
               
               
                   
                   
                 ACTCGGTATCTCTGGAGGACTCACCAACCTCGCAGCACTGGCGATATCCACAGACTTC 
               
               
                   
                   
                 GAGTCTCTATATGACGCAGTCATTGAGGCTGCGAGAATATTTGTCAGATTATGCCGTTT 
               
               
                   
                   
                 TACTTCGGTACGATCAAGAGCTATGGAGGACCGACCTGGCGTTTGGGGCTGGGCAGT 
               
               
                   
                   
                 GCTGGGAATTACACCAGAGGAACTGAGCAAAGTGCTTGAGCAGTTCCAATCCAGCATG 
               
               
                   
                   
                 GGGATTCCTGCCATCAAGAGAGCTAAGGTTGGCGTAACAGGAGACCGATGGAGCACC 
               
               
                   
                   
                 GTTATTGGGCCACCCTCAGTCTTGGACCTATTCATCCACCAGTGTCCCGCTGTGCGCA 
               
               
                   
                   
                 ACCTCCCCAAGAATGAATTGAGCATCCACGCCCTTCAGCACACAGTCACAGTCACAGA 
               
               
                   
                   
                 GGCTGACCTCGACTTCATTGTCGGGAGTGCTGAGCTTCTTAGTCACCCCATTGTGCCA 
               
               
                   
                   
                 GACTTCAAAGTCTGGGGAATGGATGATCCTGTGGCATCCTACCAGAACTGGGGAGAAA 
               
               
                   
                   
                 TGCTAAGAGCAATCGTCACTCAAGTTTTGTCCAAGCCTTTGGACATTACCAAGGTGATT 
               
               
                   
                   
                 GCGCAACTCAACACTCACCTCGGCCCTCGTCATGTCGACGTCCGAGTCATCGGACCTA 
               
               
                   
                   
                 GCAGCCACACCCCCTACTTGGCGAGTTCGCTCAAAGCTGCTGGCAGCAAGGCTATTTT 
               
               
                   
                   
                 CCAGACCGATAAGACTCTTGAGCAGTTACAGCCGAAGAAACTCCCCCCGGGCCGCATC 
               
               
                   
                   
                 GCCATTGTCGGTATGGCTGGCCGTGGTCCTGGCTGCGAGAATGTTGATGAGTTCTGG 
               
               
                   
                   
                 GACGTCATTATGGCGAAGCAGGATCGTTGTGAAGAGATTCCCAAAGATCGCTTCGACA 
               
               
                   
                   
                 TCAATGAGTTCTACTGTACCGAGCACGGGGAGGGTTGCACCACCACCACAAAATACGG 
               
               
                   
                   
                 CTGCTTCATGAACAAGCCTGGAAACTTTGACTCCCGCTTCTTCCACGTGTCGCCTCGTG 
               
               
                   
                   
                 AGGCGCTGTTGATGGACCCCGGTCACAGGCAGTTCATGATGAGCACTTATGAAGCTCT 
               
               
                   
                   
                 TGAGACGGCAGGATACTCTGATGGCCAGACTAGGGACGTTGATCCTAATAGGATCGCG 
               
               
                   
                   
                 GCGTTCTATGGCCAGTCCAACGATGATTGGCATATGGTGAGCCATTATACCCTGGGTT 
               
               
                   
                   
                 GTGATGCCTACACCCTGCAGGGGGCGCAAAGAGCCTTCGGCGCTGGTCGCATCGCCT 
               
               
                   
                   
                 TCCACTTCAAGTGGGAGGGCCCAACATACTCGCTCGATTCTGCATGTGCCTCCACCTC 
               
               
                   
                   
                 CTCTGCTATTCACCTGGCCTGCGTGAGTCTTCTATCCAAAGATGTGGACATGGCTGTTG 
               
               
                   
                   
                 TGGGTGCTGCCAACGTCGTCGGGTATCCTCACTCCTGGACAAGTCTTAGCAAGTCTGG 
               
               
                   
                   
                 TGTCTTGTCCGACACTGGAAACTGCAAAACCTACTGCGATGATGCTGATGGTTACTGCC 
               
               
                   
                   
                 GAGCAGACTTTGTCGGCTCAGTTGTGCTGAAGCGTCTCGAAGATGCTGTCGAGCAAAA 
               
               
                   
                   
                 CGACAACATCTTGGCTGTCGTGGCTGGTTCAGGCAGAAACCACTCCGGCAACTCTTCA 
               
               
                   
                   
                 TCCATCACCACGTCGGATGCCGGTGCCCAGGAGAGACTGTTTCACAAGATTATGCACA 
               
               
                   
                   
                 GCGCCAGAGTCTCTCCTGATGAGATCTCATATGTTGAGATGCACGGCACTGGAACTCA 
               
               
                   
                   
                 GATTGGCGATCCGGCCGAGATGAGTGCTGTTACCAATGTCTTCAGGAAGAGGAAGGC 
               
               
                   
                   
                 GAATAACCCCCTAACTGTTGGTGGAATCAAAGCGAACGTCGGGCATGCTGAAGCTTCT 
               
               
                   
                   
                 GCTGGCATGGCCTCCCTGCTCAAATGCATACAGATGTTCCAGAAAGATATTATGCCCC 
               
               
                   
                   
                 CTCAGGCTCGAATGCCCCATACTCTCAACCCAAAGTATCCGAGTCTTTCTGAGCTTAAC 
               
               
                   
                   
                 ATTCATATCCCCTCCGAGCCGAAGGAGTTCAAGGCTATCGGCGAGCGGCCACGACGC 
               
               
                   
                   
                 ATCCTCCTTAATAACTTTGACGCAGCAGGTGGCAACGCCTCTCTCATTCTGGAAGACTT 
               
               
                   
                   
                 CCCCTCCACCGTCAAGGAAAATGCGGACCCCAGGCCAAGCCATGTCATCGTTTCCTCT 
               
               
                   
                   
                 GCCAAAACACAATCCTCATATCACGCGAATAAGCGTAACCTCCTGAAGTGGCTACGCA 
               
               
                   
                   
                 AGAACAAAGATGCTAAACTCGAAGATGTTGCATACACAACCACCGCCCGCAGAATGCA 
               
               
                   
                   
                 CCACCCCCTCAGATTCTCTTGCAGTGCCTCCACAACGGAGGAGCTCATTTCCAAGCTT 
               
               
                   
                   
                 GAGGCAGACACGGCAGATGCAACTGCGTCTCGGGGCTCGCCCGTTGTCTTCGTATTC 
               
               
                   
                   
                 ACGGGACAGGGCTCTCACTACGCCGGCATGGGTGCCGAGTTGTACAAGACATGCCCT 
               
               
                   
                   
                 GCTTTCCGCGAGGAAGTCAACCTCTGTGCCAGCATCTCTGAGGAGCACGGGTTCCCC 
               
               
                   
                   
                 CCGTACGTGGATATCATCACCAACAAAGATGTTGACATAACCACCAAGGACACCATGCA 
               
               
                   
                   
                 GACACAGCTCGCTGTTGTCACGCTGGAGATCGCCCTCGCCGCATTCTGGAAGGCGTC 
               
               
                   
                   
                 TGGTATCCAGCCGTCAGCAGTCATGGGTCACTCCCTGGGCGAGTATGTGGCTCTCCAG 
               
               
                   
                   
                 GTCGCAGGGGTCCTATCTCTAGCTGATCTGCTCTACCTCGTCGGCAATCGGGCCCGTC 
               
               
                   
                   
                 TCCTGCTGGAGCGCTGCGAAGCCGACACCTGCGCTATGTTGGCAGTATCAAGCTCTGC 
               
               
                   
                   
                 TGCCTCCATCCGCGAGCTCATCGACCAGCGCCCGCAGTCATCCTTCGAGATTGCATGC 
               
               
                   
                   
                 AAGAATAGCCCCAATGCCACGGTTATCAGCGGCAGCACTGATGAGATTTCTGAGCTCC 
               
               
                   
                   
                 AGTCATCCTTCACGGCATCACGAGCCAGGGCTCTGTCTGTGCCCTATGGATTTCACTC 
               
               
                   
                   
                 CTTCCAGATGGATCCCATGCTCGAGGATTACATCGTTCTTGCGGGTGGTGTAACCTACT 
               
               
                   
                   
                 CGCCACCAAAGATTCCAGTTGCTTCAACCCTGCTCGCTTCGATTGTGGAGTCTTCAGG 
               
               
                   
                   
                 GGTCTTCAACGCTTCCTACCTCGGTCAGCAAACCCGCCAAGCTGTCGACTTCGTCGGT 
               
               
                   
                   
                 GCTCTTGGCGCCTTGAAGGAGAAGTTTGCTGACCCTCTCTGGCTGGAGATCGGACCCA 
               
               
                   
                   
                 GCCAAATCTGCAGCTCCTTTGTCCGGGCGACTCTCTCACCCTCGCCGGGCAAAATCTT 
               
               
                   
                   
                 GTCCACTTTGGAGGCAAATACCAACCCCTGGGCATCCATTTCCAAGTGCCTCGCCGGC 
               
               
                   
                   
                 GCGTACAAGGATGGTGTCGCAGTTGACTGGTTGGCGGTGCATGCTCCATTCAAGGGC 
               
               
                   
                   
                 GGCTTGAAGCTCGTGAAGTTGCCCGCCTATGCATGGGACCTCAAGGACTTCTGGATTG 
               
               
                   
                   
                 TCTACTCTGAGGCCAACAAGGCTGCTCGAGCTTTGGCTCCCGCTCCCTCGTTCGAAAC 
               
               
                   
                   
                 ACAGAGGATTTCTACATGTGCTCAACAGATTGTTGAAGAATCATCATCACCCAGCCTCC 
               
               
                   
                   
                 ATGTCTCTGCCCGAGCTGCTATCTCCGATCCTGGCTTCATGGCCTTGGTCGACGGTCA 
               
               
                   
                   
                 TCGCATGCGCGATGTGTCCATCTGCCCCGGAAGTGTCTTCTGCGAGGCAGGCCTTGC 
               
               
                   
                   
                 CGTCTCCAAGTACGCACTGAAGTACAGTGGCCGAAAGGATACCGTGGAAACAAGACTT 
               
               
                   
                   
                 ACAATCAACAACCTGTCTCTCAAGCGCCCGCTCACAAAGTCTCTTGTAGGCACCGATG 
               
               
                   
                   
                 GCGAGCTTCTCACCACGGTTGTTGCAGACAAGGCCTCCAGCGATACCTTGCAGGTTTC 
               
               
                   
                   
                 ATGGAAGGCTTCTTCCTCTCATGCATCATACGATCTTGGTAGCTGCGAGATCACCATTT 
               
               
                   
                   
                 GTGATGCCCAGACTCTTCAAACTAGCTGGAACAGAAGCTCATACTTCGTCAAGGCTCG 
               
               
                   
                   
                 TATGAACGAGTTGATCAAGAATGTCAAGAGCGGAAATGGTCACCGCATGCTCCCCAGT 
               
               
                   
                   
                 ATCCTCTACACTCTCTTCGCTAGCACAGTTGATTATGACCCTACCTTCAAGTCTGTCAA 
               
               
                   
                   
                 GGAGGCCTTCATCTCAAATGAGTTTGACGAAGCTGCTGCGGAGGTGGTGCTTCAGAAG 
               
               
                   
                   
                 AACCCGGCTGGAACTCAGTTCTTTGCGTCCCCTTACTGGGGTGAGAGCGTAGTTCATC 
               
               
                   
                   
                 TTGCCGGTTTCCTCGTGAACTCCAACCCTGCCCGCAAGACTGCTTCTCAGACGACCTT 
               
               
                   
                   
                 CATGATGCAGAGTCTTGAGAGCGTCGAGCAGACCGCTGATCTCGAGGCTGGACGCAC 
               
               
                   
                   
                 TTACTACACCTATGCTCGCGTTTTGCATGAGGAAGAAGACACAGTCAGCTGTGACTTGT 
               
               
                   
                   
                 TCGTCTTCGACTCGGAGAAGATGGTAATGCAGTGCTCGGGACTCTCATTCCATGAGGT 
               
               
                   
                   
                 CAGCAACAATGTTCTGGACAGACTTCTTGGAAAGGCATCACCGCCTGTGAAGCAAGTT 
               
               
                   
                   
                 TCCCACCAGAAGGCGCCAGTGCTTGTGCCCGCAGAGTCAAAACCGGCCCTGAAAGCT 
               
               
                   
                   
                 GCTGTCGAGGCGGCTCCCAAGGCGCCTGAGCCTGTGAAGACAGAGGTGAAGAAGATC 
               
               
                   
                   
                 TCTTCGTCGGAGAGCGAATTGTTCCACACTATTCTTGAAAGCATCGCCAAGGAGACTG 
               
               
                   
                   
                 GCACTCAGGTCTCTGACTTCACTGATGACATGGAACTGGCTGAACTTGGCGTTGATTC 
               
               
                   
                   
                 CATCATGGGTATTGAGATCGCTGCCGGCGTCAGCAGCAGAACCGGCCTCGATGTTCTC 
               
               
                   
                   
                 CTCCCCTCTTTTGTCGTAGATTATCCCACCATTGGAGATCTGCGAAACGAATTTGCGCG 
               
               
                   
                   
                 CTCCTCTACATCTACACCTCCCAGCAAGACCTTTTCCGAGTTCTCCATCGTCGATGCCA 
               
               
                   
                   
                 CTCCAGAGTCTACGCGCAGCTCGAGTCGAGCGCCTTCTGAGAAGAAGGAGCCTGCTC 
               
               
                   
                   
                 CGGCTTCAGAGAAGTCTGAGGAGCTGGTGATCGTTCCGTCCGCGGTTGTCGAGGATT 
               
               
                   
                   
                 CCTCTCCCCTCCCCAGTGCCAGAATCACCTTGATCCAGGGTCGATCTTCGAGTGGAAA 
               
               
                   
                   
                 GCAGCCTTTCTACTTGATCGCCGATGGAGCTGGTAGCATTGCTACGTATATCCACCTG 
               
               
                   
                   
                 GCTCCCTTCAAGGACAAGAGACCGGTTTATGGCATTGATTCGCCTTTCCTCCGTTGCC 
               
               
                   
                   
                 CCAGCAGGCTGACCACCCAGGTGGGCATTGAAGGCGTCGCAAAGATCATCTTTGAGG 
               
               
                   
                   
                 CGTTGATTAAGTGCCAGCCTGAGGGTCCCTTTGACTTGGGAGGATTCTCTGGCGGAGC 
               
               
                   
                   
                 TATGCTCAGCTATGAGGTGTCTCGCCAACTCGCTGCCGCCGGTCGCGTCGTCTCCAGT 
               
               
                   
                   
                 CTTCTCCTCATCGATATGTGTTCTCCCCGTCCTTTGGGTGTTGAGGACACAATCGAGGT 
               
               
                   
                   
                 CGGCTGGAAGGTCTACGAGACCATCGCTTCCCAAGATAAGCTCTGGAACGCCTCAAGT 
               
               
                   
                   
                 AACACCCAGCAGCATCTCAAGGCCGTCTTCGCCTGCGTCGCAGCCTACCACCCTCCTC 
               
               
                   
                   
                 CCATGACTCCCGCTCAACGACCCAAGCGAACAGCTATCATCTGGGCTAAAAAGGGCAT 
               
               
                   
                   
                 GGTCGACCGTTGTTCTCGCGACGAGAAGGTGATGAAGTTCCTGGCCGACAAGGGCAT 
               
               
                   
                   
                 CCCCACCGAGTCGTACCCAGGGTTCATGGAGGACCCCAAGCTGGGTGCCGTGGCGTG 
               
               
                   
                   
                 GGGCCTTCCGCACAAGTCCGCTGCGGACTTGGGACCCAACGGATGGGACAAGTTCCT 
               
               
                   
                   
                 TGGCGAGACTCTGTGCCTGTCTATCGATTCGGACCACTTGGATATGCCGATGCCGGGG 
               
               
                   
                   
                 CATGTGCACTTGCTTCAGGCGGCGATGGAGGAGTCGTTCAAATATTTCAGCGAGGCAA 
               
               
                   
                   
                 ATTAG 
               
               
                   
               
               
                 65 
                 pCHIDT-2.1 
                 TATCTAAAAATTGCCTTATGATCCGTCTCTCCGGTTACAGCCTGTGTAACTGATTAATCC 
               
               
                   
                   
                 TGCCTTTCTAATCACCATTCTAATGTTTTAATTAAGGGATTTTGTCTTCATTAACGGCTTT 
               
               
                   
                   
                 CGCTCATAAAAATGTTATGACGTTTTGCCCGCAGGCGGGAAACCATCCACTTCACGAG 
               
               
                   
                   
                 ACTGATCTCCTCTGCCGGAACACCGGGCATCTCCAACTTATAAGTTGGAGAAATAAGA 
               
               
                   
                   
                 GAATTTCAGATTGAGAGAATGAAAAAAAAAAAAAAAAAAAAGGCAGAGGAGAGCATAGA 
               
               
                   
                   
                 AATGGGGTTCACTTTTTGGTAAAGCTATAGCATGCCTATCACATATAAATAGAGTGCCA 
               
               
                   
                   
                 GTAGCGACTTTTTTCACACTCGAAATACTCTTACTACTGCTCTCTTGTTGTTTTTATCACT 
               
               
                   
                   
                 TCTTGTTTCTTCTTGGTAAATAGAATATCAAGCTACAAAAAGCATACAATCAACTATCAA 
               
               
                   
                   
                 CTATTAACTATATCGTAATACACAATGCTGGGATTCCCAATGTTCAACCCAGCTACGCC 
               
               
                   
                   
                 TGATGTCTGGAAGATGAATACCCCTTACTTTCCATTTGTTACACCGGGGTTATTTCCTG 
               
               
                   
                   
                 CCTCAGCACCCCCATCGCCCACCAACGTAGATGCCGAAGCTGCCAGTTCCCAACAGTC 
               
               
                   
                   
                 GGAAGCAAGCTATCTGGATAAGGAGAAAATTGTTCGAGGGCCACTTGATTATCTTCTCA 
               
               
                   
                   
                 AATCCCCTGGAAAAGACATTCGTCGGAAATTCATTCACGCGTTCAATGAATGGCTGCGC 
               
               
                   
                   
                 ATTCCTGAGGACAAGTTGAATATTATCACGGAAATTGTTGGATTGCTTCACACGGCCTC 
               
               
                   
                   
                 CCTTCTAATCGACGATATTCAGGACAATTCCAAGCTTCGACGCGGCCTCCCAGTGGCC 
               
               
                   
                   
                 CATAGCATATTTGGTATTGCGCAGACAATTAACTCTGCCAATTATGCGTACTTTCTAGCC 
               
               
                   
                   
                 CAGGAAAGGCTCCGCGAACTGAATCATCCTGAAGCGTACGAAATATACACAGAGGAAC 
               
               
                   
                   
                 TGCTTCGTCTGCACCGCGGTCAAGGTATGGACTTGTACTGGCGGGACTGCCTAACCTG 
               
               
                   
                   
                 TCCCACAGAGGAGGACTATATTGAGATGATCGCCAACAAGACTGGTGGCCTATTTCGA 
               
               
                   
                   
                 CTGGCGATTAAGCTTATGCAGTTGGAAAGCACTTTGTGCAGCAATGTCATTGAACTAGC 
               
               
                   
                   
                 AGACTTGTTGGGCGTGATCTTTCAGATTCGGGATGATTACCAAAACTTACAGAGTGGAC 
               
               
                   
                   
                 TATACGCCAAGAACAAGGGATTTTGCGAGGATTTGACGGAGGGAAAATTTTCCTTTCTG 
               
               
                   
                   
                 ATTATCCACAGTATTAACAGTAACCCGAACAATCACCATCTGCTAAATATACTACGGCA 
               
               
                   
                   
                 GCGGAGCGAGGACGATTCGGTGAAGAAGTATGCTGTTGATTATATCGACTCGACGGG 
               
               
                   
                   
                 GAGTTTTGACTACTGCCGGGAACGGCTCGCTTCCTTATTGGAAGAGGCGGATCAAATG 
               
               
                   
                   
                 GTTAAGAAGTTGGAAAATGAGGGGGGACAATCAAAGGGGATCTACGATATTCTGAGCT 
               
               
                   
                   
                 TTCTGTCGTGAGCGGATCTCTTATGTCTTTACGATTTATAGTTTTCATTATCAAGTATGC 
               
               
                   
                   
                 CTATATTAGTATATAGCATCTTTAGATGACAGTGTTCGAAGTTTCACGAATAAAAGATAA 
               
               
                   
                   
                 TATTCTACTTTTTGCTCCCACCGCGTTTGCTAGCACGAGTGAACACCATCCCTCGCCTG 
               
               
                   
                   
                 TGAGTTGTACCCATTCCTCTAAACTGTAGACATGGTAGCTTCAGCAGTGTTCGTTATGT 
               
               
                   
                   
                 ACGGCATCCTCCAACAAACAGTCGGTTATAGTTTGTCCTGCTCCTCTGAATCGTCTCCC 
               
               
                   
                   
                 TCGATATTTCTCATTTTCCTTCGCATGCCAGCATTGAAATGATCGAAGTTCAATGATGAA 
               
               
                   
                   
                 ACGGTAATTCTTCTGTCATTTACTCATCTCATCTCATCAAGTTATATAATTCTATACGGAT 
               
               
                   
                   
                 GTAATTTTTCACTTTTCGTCTTGACGTCCACCCTATAATTTCAATTATTGAACCCTCACG 
               
               
                   
                   
                 ATCCAGTTCTCCAGTGACACAGCCTTTATCTGGTCAAACCTTTCTTTCTAATCACCTATG 
               
               
                   
                   
                 CTGATGCTTAATTAAGGGATTTTTGTCTCCATCAACGGCATGCGCCCAAAAATGACGTT 
               
               
                   
                   
                 TTTTTTAACCCATAGACACGAAACTACCCATTTTCCACCGGCCTGACCTACCACCGGAA 
               
               
                   
                   
                 CAACGGCCATCTCCAACTTGCAAGTTGGGGAAATTAAGAGCATCGCAGGTTTAATGGA 
               
               
                   
                   
                 AGAAAAAAAAAAGGTACAGCACAGCGCAAATGGAGTTAGTTCCCTTATGTCACACACTC 
               
               
                   
                   
                 ACACACAGTCGGTCAGATCAAGCATACTGGGTGCGTATAAATAGAGTGGCCATTGCCA 
               
               
                   
                   
                 CCCTGTTTATCTCAAAATCTGTCTTGTTAGTGGTCTTCTCCCTTTTTCAGGTTACAATTCT 
               
               
                   
                   
                 CTTGTTTCTACTTAGTATATAAGTATATCAAGCTATATTAAGCATACTATCAACTGTCAAC 
               
               
                   
                   
                 TCTATCCTCAAAATACAATACAAAATGGATGGGTTCGACCATTCTACTGCTCCACCAGG 
               
               
                   
                   
                 ATATAACGAGCTAAAATGGCTCGCCGATATCTTCGTCATCGGAATGGCTGTTGGCTGG 
               
               
                   
                   
                 GTTGCTCACTATATGGAGATGATTCACACGTCGTTCAAGGACCAAACATACTGCATGAC 
               
               
                   
                   
                 CATCGGGGGCCTTTGCATCAATTTTGCCTGGGAAATCATATTCTGCACAATGTATCCTG 
               
               
                   
                   
                 CCAAAGGATTTGTCGAGCGGGTTGCCTTTCTCATGGGCATTTCTCTCGACCTTGGGGT 
               
               
                   
                   
                 TATTTACGCGGGAATCAAGAACGCCCCAAATGAATGGCACCACTCTGCAATGGTGAGG 
               
               
                   
                   
                 GACCATATGCCCCTTGTCTTCGCAGCAACGACACTTTGTTGTCTGAGCGGTCATATGG 
               
               
                   
                   
                 CTCTTACTGCCCAGGTTGGTCCCGCACAAGCCTATACGTGGGGGGCAATTGCATGCCA 
               
               
                   
                   
                 GCTCTTTATCAGCATAGGGAATGTGTTTCAATTGTTGAGTCGGGGAAACACACGAGGG 
               
               
                   
                   
                 GCGTCATGGACGCTATGGACCTCCAGGTTTTTTGGATCAACATCAGCCATTGGCTTTGC 
               
               
                   
                   
                 TCTTGTTCGATATATTCGCTGGTGGGAGGCCTTTTCTTGGTTGAACTGCCCGCTTGTGA 
               
               
                   
                   
                 TATGGTCCGTGGCCATGTTCTTTCTGTTTGAAACACTCTATGGAGCCCTATTCTATTCTG 
               
               
                   
                   
                 TCAAGCGACAAGAAGGGAGATCCCAGCGTGGAATCAAGCACAAAGAGAGGTAGACAA 
               
               
                   
                   
                 ATCGCTCTTAAATATATACCTAAAGAACATTAAAGCTATATTATAAGCAAAGATACGTAA 
               
               
                   
                   
                 ATTTTGCTTATATTATTATACACATATCATATTTCTATATTTTTAAGATTTGGTTATATAAT 
               
               
                   
                   
                 GTACGTAATGCAAAGGAAATAAATTTTATACATTATTGAACAGCGTCCAAGTAACTACAT 
               
               
                   
                   
                 TATGTGCACTAATAGTTTAGCGTCGTGAAGACTTTATTGTGTCGCGAAAAGTAAAAATTT 
               
               
                   
                   
                 TAAAAATTAGAGCACCTTGAACTTGCGAAAAAGGTTCTCATCAACTGTTTAAAAGGAGG 
               
               
                   
                   
                 ATATCAGGTCCTATTTCTGACAAACAATATACAAATTTAGTTTCAAAGATGAATCAGTGC 
               
               
                   
                   
                 GCGAAGGACATAACTCAATAGGAAAAAACCGAGCTTCCTTTCATCCGGCGCGGCTGTG 
               
               
                   
                   
                 TTCTACATATCACTGAAGCTCCGGGTATTTTAAGTTATACAAGGGAAAGATGCCGGCTA 
               
               
                   
                   
                 GACTAGCAAGTTTTAGGCTGCTTAACATTATGGATAGGCGGATAAAGGGCCCAAACAG 
               
               
                   
                   
                 GATTGTAAAGCTTAGACGCTTCTGGTTGGACAATGGTACGTTTGTGTATTAAGTAAGGC 
               
               
                   
                   
                 TTGGCTGGGGATAGCAACATTGGGCAGAGTATAGAAGACCACAAAAAAAAGGTATATA 
               
               
                   
                   
                 AGGGCAGAGAAGTCTTTGTTAATGTGTGTAACTTCTCTTCCATGTGTAATCAGTATTTCTA 
               
               
                   
                   
                 CTTACTTCTTAAATATACAGAAGTAAGACAGATAACCAACAGCCTTTCCCAGATATACAT 
               
               
                   
                   
                 ATATATCTTTATTTCAGCTTAAACAATAATTATATTTGTTTAACTCAAAAATAAAAAAAAAA 
               
               
                   
                   
                 AACCAAACTCACGCAACTAATTATTCCATAATAAAATAACAACATGGCGGCACTTCCGG 
               
               
                   
                   
                 ACGTTGCCTCCATTCCCATCCCTCTGGTGGCAACCCTAGGCATTGCCCCTCTAATTTTC 
               
               
                   
                   
                 TATCTCGTCCTTGATAGAATTAGCCCCTTGTGGCCAAATTCCAAAGCTTTCCTGATTGG 
               
               
                   
                   
                 CAAGAAGAAACCGGAGACCGTGACATCGTTCGAGTGCCCATATGCCTACATCCGTCAG 
               
               
                   
                   
                 ATCTATGGGAAGTATCACTGGGAGCCATTCGTACAGAAGCTGTCTCCGAGGCTTAAGG 
               
               
                   
                   
                 ATGAGGATCCGGCCAAATATAAGATGGTTCTGGAGATAATGGATGCAATCCACCTGTGT 
               
               
                   
                   
                 CTGATGCTAGTTGACGATATAACTGACAATAGCGACTATCGAAAAGGCAAGCCAGCAG 
               
               
                   
                   
                 CCCACCGGATATATGGCCCTTCAGAGACAGCAAATCGCGCTTACTACCGAGTCACCCA 
               
               
                   
                   
                 GATTCTAAACAAGACCGTGCAAAAGTTCCCCAAGCTGGCCAAGTTCCTGCTTCAGAATC 
               
               
                   
                   
                 TGGAAGAAATTCTCGAAGGCCAAGACCTGTCAGTAATCTGGCGACGGGATGGAGTGGG 
               
               
                   
                   
                 TAGCCTTTCGACTGTTCCTGATGAGCGAGTTGCAGCCTATCGCAAGATGGCGTCATTG 
               
               
                   
                   
                 AAAACTGGGGCGTTATTCCGGGTGCTGGGGCAATTGGTGATGGAGGACCAATCGATG 
               
               
                   
                   
                 GACGGGACGATGACTACTCTTGCGTGGTGCTCTCAGCTGCAGAATGACTGCAAGAATG 
               
               
                   
                   
                 TCTACTCATCTGAATATGCTAAGGCCAAAGGGGCGCTTGCCGAAGACCTCCGAAATCG 
               
               
                   
                   
                 AGAGCTCTCATTTCCAATTATCCTCGCGCTGGAAGCTCCTGAAGGGCATTGGGTCGCC 
               
               
                   
                   
                 AGTGCTTTGGAGACCAGCTCACCGCGCAACATTCGCAAGGCGCTTGCTGTGATTCAGA 
               
               
                   
                   
                 GTGAGAGAGTGCGCAATGCTTGTTTCAAGGAGCTCAAGTCGGCGAGTGCTTCGGTCCA 
               
               
                   
                   
                 GGACTGGTTGGCTATTTGGGGACGGAACGAGAAAATGAACTTGAAGAGCCAGCAGAC 
               
               
                   
                   
                 GTAGAGTGCTTTTAACTAAGAATTATTAGTCTTTTCTGCTTATTTTTTCATCATAGTTTAG 
               
               
                   
                   
                 AACACTTTATATTAACGAATAGTTTATGAATCTATTTAGGTTTAAAAATTGATACAGTTTT 
               
               
                   
                   
                 ATAAGTTACTTTTTCAAAGACTCGTGCTGTCTATTGCATAATGCACTGGAAGGGGAAAA 
               
               
                   
                   
                 AAAAGGTGCACACGCGTGGCTTTTTCTTGAATTTGCAGTTTGAAAAATAACTACATGGA 
               
               
                   
                   
                 TGATAAGAAAACATGGAGTACAGTCACTTTGAGAACCTTCAATCAGCTGGTAACGTCTT 
               
               
                   
                   
                 CGTTAATTGGATACTCAAAAAAGATGGATAGCATGAATCACAAGATGGAAGGAAATGCG 
               
               
                   
                   
                 GGCCACGACCACAGTGATATGCATATGGGAGATGGAGATGATACCTCCATTGGGCCGA 
               
               
                   
                   
                 TGAAGTTAGTCGACGGATAGAAGCGGTTGTCCCCTTTCCCGGCGAGCCGGCAGTCGG 
               
               
                   
                   
                 GCCGAGGTTCGGATAAATTTTGTATTGTGTTTTGATTCTGTCATGAGTATTACTTATGTT 
               
               
                   
                   
                 CTCTTTAGGTAACCCCAGGTTAATCAATCACAGTTTCATACCGGCTAGTATTCAAATTAT 
               
               
                   
                   
                 GACTTTTCTTCTGCAGTGTCAGCCTTACGACGATTATCTATGAGCTTTGAATATAGTTTG 
               
               
                   
                   
                 CCGTGATTCGTATCTTTAATTGGATAATAAAATGCGAAGGATCGATGACCCTTATTATTA 
               
               
                   
                   
                 TTTTTCTACACTGGCTACCGATTTAACTCATCTTCTTGAAAGTATATAAGTAACAGTAAAA 
               
               
                   
                   
                 TATACCGTACTTCTGCTAATGTTATTTGTCCCTTATTTTTCTTTTCTTGTCTTATGCTATA 
               
               
                   
                   
                 GTACCTAAGAATAACGACTATTGTTTTGAACTAAACAAAGTAGTAAAAGCACATAAAAGA 
               
               
                   
                   
                 ATTAAGAAAATGGCCAATGCCCAGCAACCCCCCGTTTCGCATCCTTATTGTGGGCGGTTC 
               
               
                   
                   
                 TGTCGCAGGCCTCATCCTTGCGCACTGTCTCGAACGCGCCAATATAGAGTACCTCATA 
               
               
                   
                   
                 CTCGAAAAAGGAGAAGATGTTGCTCCACAAGTTGGTGCGTCGATAGGTATCATGCCAA 
               
               
                   
                   
                 ATGGCGGACGGATCCTCGAGCAACTGGGCCTATTTGGGGAGATTGAGCGTGTGATCG 
               
               
                   
                   
                 AGCCGTTGCATCAGGCGAATATCAGCTATCCAGATGGGTTCTGCTTTAGTAACGTCTAT 
               
               
                   
                   
                 CCTAAGGTTCTTGGCGACAGGTTCGGATACCCGGTTGCATTCTTGGACCGGCAGAAGT 
               
               
                   
                   
                 TCCTGCAGATTGCATATGAGGGGCTGAGAAAGAAGCAGAATGTTCTCACCGGTAAAAG 
               
               
                   
                   
                 GGTAGTTGGACTGCGACAGTCGGATCAAGGGACTGCTGTTTCTGTGGCTGACGGGAC 
               
               
                   
                   
                 AGAGTATGAGGCGGATCTCGTGGTTGGTGCTGATGGAGTACATAGTCGGGTGAGAAGT 
               
               
                   
                   
                 GAGATTTGGAAGATGGCGGAAGAGAATCAGCCTGCATCAGTTTCGACACGTGAAAGAA 
               
               
                   
                   
                 GAAGCATGACTGTTGAATATGTCTGCGTTTTCGGGATTTCATCAGCCATCCCAGGGCTC 
               
               
                   
                   
                 GAGATAAGCGAACAGATCAACGGTATTTTCGACCATCTATCCATTCTAACAATCCATGG 
               
               
                   
                   
                 CAGACATGGTCGCGTGTTCTGGTTCGTGATCCAGAAGCTGGATAGGAAGTACGTCTAT 
               
               
                   
                   
                 CCTGATGTCCCGCGATTCTCAGACGAGGATGCCGTACAGCTCTTCGATCGGGTCAAAC 
               
               
                   
                   
                 ACGTGCGGTTCTGGAAAAACATCTGTGTGGGGGACTTGTGGAAGAACAGAGAGGTGTC 
               
               
                   
                   
                 CTCGATGACAGCGCTGGAGGAGGGAGTGTTCGAGACATGGCATCATGATAGGATGGT 
               
               
                   
                   
                 TTTGATTGGAGATAGCGTTCACAAGATGACGCCCAACTTTGGCCAAGGAGCTAATTCAG 
               
               
                   
                   
                 CCATCGAGGATGCTGCCGCGCTCTCTTCCCTTCTACATGATCTCGTCAACGCCCGTGG 
               
               
                   
                   
                 AGTTTGCAAGCCATCGAATGTCCAGATTCAGCATCTCCTCAAGCAGTATCGGGAGACC 
               
               
                   
                   
                 CGATACACTCGCATGGTAGGCATGTGTCGCACCGCGGCTTCAGTCTCTCGGATTCAGG 
               
               
                   
                   
                 CCCGAGATGGCATCCTCAACACCGTCTTTGGACGATATTGGGCACCTTATGCTGGCAA 
               
               
                   
                   
                 CCTGCCTGCTGACCTGGCATCAAAAGTGATGGCAGATGCAGAGGTTGTTACTTTTCTG 
               
               
                   
                   
                 CCCTTGCCAGGGCGCTCAGGACCGGGCTGGGAGATGTACAGACGAAAGGGGAAGGG 
               
               
                   
                   
                 AGGGCAGGTGCAATGGGTGCTTATAATCTTAAGCTTACTTACGATTGGTGGATTGTGCA 
               
               
                   
                   
                 TCTGGCTACAAAGCAATGCGTTGAGTAGATAAGGAGATTGATAAGACTTTTCTAGTTGC 
               
               
                   
                   
                 ATATCTTTTATATTTAAATCTTATCTATTAGTTAATTTTTTGTAATTTATCCTTATATATAGT 
               
               
                   
                   
                 CTGGTTATTCTAAAATATCATTTCAGTATCTAAAAATTCCCCTCTTTTTTCAGTTATATCTT 
               
               
                   
                   
                 AACAGGCGACAGTCCAAATGTTGATTTATCCCAGTCCGATTCATCAGGGTTGTGAAGCA 
               
               
                   
                   
                 TTTTGTCAATGGTCGAAATCACATCAGTAATAGTGCCTCTTACTTGCCTCATAGAATTTC 
               
               
                   
                   
                 TTTCTCTTAACGTCACCGTTTGGTCTTTTATAGTTTCGAAATCTATGGTGATACCAAATG 
               
               
                   
                   
                 GTGTTCCCAATTCATCGTTACGGGCGTATTTTTTACCAATTGAAGTATTGGAATCGTCAA 
               
               
                   
                   
                 TTTTAAAGTATATCTCTCTTTTACGTAAAGCCTGCGAGATCCTCTTAAGTATAGCGGGGA 
               
               
                   
                   
                 AGCCATCGTTATTCGATATTGTCGTAACAAATACTTTGATCGGCGCTATGCGGCCGCCA 
               
               
                   
                   
                 CCGCGGTGGAGCTCCAGCTTTTGTTCCCTTTAGTGAGGGTTAATTGCGCGCTTGGCGT 
               
               
                   
                   
                 AATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACA 
               
               
                   
                   
                 TAGGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGGTAACTCAC 
               
               
                   
                   
                 ATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTG 
               
               
                   
                   
                 CATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCC 
               
               
                   
                   
                 GCTTCCTCGCTCACTGACTCGCTGCGGTCGGTCGTTCGGCTGCGGCGAGCGGTATCA 
               
               
                   
                   
                 GCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGA 
               
               
                   
                   
                 ACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGG 
               
               
                   
                   
                 CGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCA 
               
               
                   
                   
                 GAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTC 
               
               
                   
                   
                 CCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTC 
               
               
                   
                   
                 CCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGT 
               
               
                   
                   
                 AGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCT 
               
               
                   
                   
                 GCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCC 
               
               
                   
                   
                 ACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTAC 
               
               
                   
                   
                 AGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGGACAGTATTTGGTATCT 
               
               
                   
                   
                 GCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAA 
               
               
                   
                   
                 ACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGA 
               
               
                   
                   
                 AAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAA 
               
               
                   
                   
                 CGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGA 
               
               
                   
                   
                 TCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTC 
               
               
                   
                   
                 TGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTT 
               
               
                   
                   
                 CATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACC 
               
               
                   
                   
                 ATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAGATTTA 
               
               
                   
                   
                 TCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTAT 
               
               
                   
                   
                 CCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTT 
               
               
                   
                   
                 AATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTCGTCGTT 
               
               
                   
                   
                 TGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCC 
               
               
                   
                   
                 ATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTT 
               
               
                   
                   
                 GGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGC 
               
               
                   
                   
                 CATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAG 
               
               
                   
                   
                 TGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCA 
               
               
                   
                   
                 CATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTC 
               
               
                   
                   
                 AAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGAT 
               
               
                   
                   
                 CTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAAT 
               
               
                   
                   
                 GCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCATACTCTTCCTTTT 
               
               
                   
                   
                 TCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATG 
               
               
                   
                   
                 TATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTG 
               
               
                   
                   
                 AACGAAGCATCTGTGCTTCATTTTGTAGAACAAAAATGCAACGCGAGAGCGCTAATTTT 
               
               
                   
                   
                 TCAAACAAAGAATCTGAGCTGCATTTTTACAGAACAGAAATGCAACGCGAAAGCGCTAT 
               
               
                   
                   
                 TTTACCAACGAAGAATCTGTGCTTCATTTTTGTAAAACAAAAATGCAACGCGAGAGCGC 
               
               
                   
                   
                 TAATTTTTCAAACAAAGAATCTGAGCTGCATTTTTACAGAACAGAAATGCAACGCGAGA 
               
               
                   
                   
                 GCGCTATTTTACCAACAAAGAATCTATACTTCTTTTTTGTTCTACAAAAATGCATCCCGA 
               
               
                   
                   
                 GAGCGCTATTTTTCTAACAAAGCATCTTAGATTACTTTTTTTCTCCTTTGTGCGCTCTATA 
               
               
                   
                   
                 ATGCAGTCTCTTGATAACTTTTTGCACTGTAGGTCCGTTAAGGTTAGAAGAAGGCTACT 
               
               
                   
                   
                 TTGGTGTCTATTTTCTCTTCCATAAAAAAAGCCTGACTCCACTTCCCGCGTTTACTGATT 
               
               
                   
                   
                 ACTAGCGAAGCTGCGGGTGCATTTTTTCAAGATAAAGGCATCCCCGATTATATTCTATA 
               
               
                   
                   
                 CCGATGTGGATTGCGCATACTTTGTGAACAGAAAGTGATAGCGTTGATGATTCTTCATT 
               
               
                   
                   
                 GGTCAGAAAATTATGAACGGTTTCTTCTATTTTGTCTCTATATACTACGTATAGGAAATG 
               
               
                   
                   
                 TTTACATTTTCGTATTGTTTTCGATTCACTCTATGAATAGTTCTTACTACAATTTTTTTGTC 
               
               
                   
                   
                 TAAAGAGTAATACTAGAGATAAACATAAAAAATGTAGAGGTCGAGTTTAGATGCAAGTT 
               
               
                   
                   
                 CAAGGAGCGAAAGGTGGATGGGTAGGTTATATAGGGATATAGCACAGAGATATATAGC 
               
               
                   
                   
                 AAAGAGATACTTTTGAGCAATGTTTGTGGAAGCGGTATTCGCAATATTTTAGTAGCTCG 
               
               
                   
                   
                 TTACAGTCCGGTGCGTTTTTGGTTTTTTGAAAGTGCGTCTTCAGAGCGCTTTTGGTTTTC 
               
               
                   
                   
                 AAAAGCGCTCTGAAGTTCCTATACTTTCTAGAGAATAGGAACTTCGGAATAGGAACTTC 
               
               
                   
                   
                 AAAGCGTTTCCGAAAACGAGCGCTTCCGAAAATGCAACGCGAGCTGCGCACATACAGC 
               
               
                   
                   
                 TCACTGTTCACGTCGCACCTATATCTGCGTGTTGCCTGTATATATATATACATGAGAAGA 
               
               
                   
                   
                 ACGGCATAGTGCGTGTTTATGCTTAAATGCGTACTTATATGCGTCTATTTATGTAGGATG 
               
               
                   
                   
                 AAAGGTAGTCTAGTACCTCCTGTGATATTATCCCATTCCATGCGGGGTATCGTATGCTT 
               
               
                   
                   
                 CCTTCAGCACTACCCTTTAGCTGTTCTATATGCTGCCACTCCTCAATTGGATTAGTCTCA 
               
               
                   
                   
                 TCCTTCAATGCTATCATTTCCTTTGATATTGGATCATACTAAGAAACCATTATTATCATGA 
               
               
                   
                   
                 CATTAACCTATAAAAATAGGCGTATCACGAGGCCCTTTCGTCTCGCGCGTTTCGGTGAT 
               
               
                   
                   
                 GACGGTGAAAACCTCTGACACATGCAGCTCCCGGAGACGGTCACAGCTTGTCTGTAAG 
               
               
                   
                   
                 CGGATGCCGGGAGCAGACAAGCCCGTCAGGGCGCGTCAGCGGGTGTTGGCGGGTGT 
               
               
                   
                   
                 CGGGGCTGGCTTAACTATGCGGCATCAGAGCAGATTGTACTGAGAGTGCACCATATCG 
               
               
                   
                   
                 ACTACGTCGTAAGGCCGTTTCTGACAGAGTAAAATTCTTGAGGGAACTTTCACCATTAT 
               
               
                   
                   
                 GGGAAATGCTTCAAGAAGGTATTGACTTAAACTCCATCAAATGGTCAGGTCATTGAGTG 
               
               
                   
                   
                 TTTTTTATTTGTTGTATTTTTTTTTTTTTAGAGAAAATCCTCCAATATCAAATTAGGAATCG 
               
               
                   
                   
                 TAGTTTCATGATTTTCTGTTACACCTAACTTTTTGTGTGGTGCCCTCCTCCTTGTCAATA 
               
               
                   
                   
                 TTAATGTTAAAGTGCAATTCTTTTTCCTTATCACGTTGAGCCATTAGTATCAATTTGCTTA 
               
               
                   
                   
                 CCTGTATTCCTTTACTATCCTCCTTTTTCTCCTTCTTGATAAATGTATGTAGATTGCGTAT 
               
               
                   
                   
                 ATAGTTTCGTCTACCCTATGAACATATTCCATTTTGTAATTTCGTGTCGTTTCTATTATGA 
               
               
                   
                   
                 ATTTCATTTATAAAGTTTATGTACAAATATCATAAAAAAAGAGAATCTTTTTAAGCAAGGA 
               
               
                   
                   
                 TTTTCTTAACTTCTTCGGCGACAGCATCACCGACTTCGGTGGTACTGTTGGAACCACCT 
               
               
                   
                   
                 AAATCACCAGTTCTGATACCTGCATCCAAAACCTTTTTAACTGCATCTTCAATGGCCTTA 
               
               
                   
                   
                 CCTTCTTCAGGCAAGTTCAATGACAATTTCAACATCATTGCAGCAGACAAGATAGTGGC 
               
               
                   
                   
                 GATAGGGTCAACCTTATTCTTTGGCAAATCTGGAGCAGAACCGTGGCATGGTTCGTAC 
               
               
                   
                   
                 AAACCAAATGCGGTGTTCTTGTCTGGCAAAGAGGCCAAGGACGCAGATGGCAACAAAC 
               
               
                   
                   
                 CCAAGGAACCTGGGATAACGGAGGCTTCATCGGAGATGATATCACCAAACATGTTGCT 
               
               
                   
                   
                 GGTGATTATAATACCATTTAGGTGGGTTGGGTTCTTAACTAGGATCATGGCGGCAGAAT 
               
               
                   
                   
                 CAATCAATTGATGTTGAACCTTCAATGTAGGGAATTCGTTCTTGATGGTTTCCTCCACAG 
               
               
                   
                   
                 TTTTTCTCCATAATCTTGAAGAGGCCAAAAGATTAGCTTTATCCAAGGACCAAATAGGCA 
               
               
                   
                   
                 ATGGTGGCTCATGTTGTAGGGCCATGAAAGCGGCCATTCTTGTGATTCTTTGCACTTCT 
               
               
                   
                   
                 GGAACGGTGTATTGTTCACTATCCCAAGCCACACCATCACCATCGTCTTCCTTTCTCTT 
               
               
                   
                   
                 ACCAAAGTAAATACCTCCCACTAATTCTCTGACAACAACGAAGTCAGTACCTTTAGCAA 
               
               
                   
                   
                 ATTGTGGCTTGATTGGAGATAAGTCTAAAAGAGAGTCGGATGCAAAGTTACATGGTCTT 
               
               
                   
                   
                 AAGTTGGCGTACAATTGAAGTTCTTTACGGATTTTTAGTAAACCTTGTTCAGGTCTAACA 
               
               
                   
                   
                 CTACCGGTACCCCATTTAGGACCAGCCACAGCACCTAACAAAACGGCATCAACCTTCTT 
               
               
                   
                   
                 GGAGGCTTCCAGCGCCTCATCTGGAAGTGGGACACCTGTAGCATCGATAGCAGCACC 
               
               
                   
                   
                 ACCAATTAAATGATTTTCGAAATCGAACTTGACATTGGAACGAACATCAGAAATAGCTTT 
               
               
                   
                   
                 AAGAACCTTAATGGCTTCGGCTGTGATTTCTTGACCAACGTGGTCACCTGGCAAAACGA 
               
               
                   
                   
                 CGATCTTCTTAGGGGCAGACATAGGGGCAGACATTAGAATGGTATATCCTTGAAATATA 
               
               
                   
                   
                 TATATATATTGCTGAAATGTAAAAGGTAAGAAAAGTTAGAAAGTAAGACGATTGCTAACC 
               
               
                   
                   
                 ACCTATTGGAAAAAACAATAGGTCCTTAAATAATATTGTCAACTTCAAGTATTGTGATGC 
               
               
                   
                   
                 AAGCATTTAGTCATGAACGCTTCTCTATTCTATATGAAAAGCCGGTTCCGGCCTCTCAC 
               
               
                   
                   
                 CTTTCCTTTTTCTCCCAATTTTTCAGTTGAAAAAGGTATATGCGTCAGGCGACCTCTGAA 
               
               
                   
                   
                 ATTAACAAAAAATTTCCAGTCATCGAATTTGATTCTGTGCGATAGCGCCCCTGTGTGTTC 
               
               
                   
                   
                 TCGTTATGTTGAGGAAAAAAATAATGGTTGCTAAGAGATTCGAACTCTTGCATCTTACGA 
               
               
                   
                   
                 TACCTGAGTATTCCCACAGTTAACTGCGGTCAAGATATTTCTTGAATCAGGCGCCTTAG 
               
               
                   
                   
                 ACCGCTCGGCCAAACAACCAATTACTTGTTGAGAAATAGAGTATAATTATCCTATAAATA 
               
               
                   
                   
                 TAACGTTTTTGAACACACATGAACAAGGAAGTACAGGACAATTGATTTTGAAGAGAATG 
               
               
                   
                   
                 TGGATTTTGATGTAATTGTTGGGATTCCATTTTTAATAAGGCAATAATATTAGGTATGTG 
               
               
                   
                   
                 GATATACTAGAAGTTCTCCTCGACCGTCGATATGCGGTGTGAAATACCGCACAGATGC 
               
               
                   
                   
                 GTAAGGAGAAAATACCGCATCAGGAAATTGTAAACGTTAATATTTTGTTAAAATTCGCGT 
               
               
                   
                   
                 TAAATTTTTGTTAAATCAGCTCATTTTTTAACCAATAGGCCGAAATCGGCAAAATCCCTT 
               
               
                   
                   
                 ATAAATCAAAAGAATAGACCGAGATAGGGTTGAGTGTTGTTCCAGTTTGGAACAAGAGT 
               
               
                   
                   
                 CCACTATTAAAGAACGTGGACTCCAACGTCAAAGGGCGAAAAACCGTCTATCAGGGCG 
               
               
                   
                   
                 ATGGCCCACTACGTGAACCATCACCCTAATCAAGTTTTTTGGGGTCGAGGTGCCGTAA 
               
               
                   
                   
                 AGCACTAAATCGGAACCCTAAAGGGAGCCCCCGATTTAGAGCTTGACGGGGAAAGCC 
               
               
                   
                   
                 GGCGAACGTGGCGAGAAAGGAAGGGAAGAAAGCGAAAGGAGCGGGCGCTAGGGCGC 
               
               
                   
                   
                 TGGCAAGTGTAGCGGTCACGCTGCGCGTAACCACCACACCCGCCGCGCTTAATGCGC 
               
               
                   
                   
                 CGCTACAGGGCGCGTCGCGCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGC 
               
               
                   
                   
                 GATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAA 
               
               
                   
                   
                 GGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACGACGTTGTAAAACGACGGC 
               
               
                   
                   
                 CAGTGAGCGCGCGTAATACGACTCACTATAGGGCGAATTGGGTACCGGGCCCCCCCT 
               
               
                   
                   
                 CGAGGTCGACGGTATCGATAAGCTTGATATCGAATTCCTGCAGCCCGGGGGATCCACT 
               
               
                   
                   
                 AGTTCTAGATTAATTAA 
               
               
                   
               
               
                 66 
                 pCHIDT-2c 
                 ATAGCTTCAAAATGTTTCTACTCCTTTTTTACTCTTCCAGATTTTCTCGGACTCCGCGCA 
               
               
                   
                   
                 TCGCCGTACCACTTCAAAACACCCAAGCACAGCATACTAAATTTCCCCTCTTTCTTCCT 
               
               
                   
                   
                 CTAGGGTGTCGTTAATTACCCGTACTAAAGGTTTGGAAAAGAAAAAAGAGACCGCCTC 
               
               
                   
                   
                 GTTTCTTTTTCTTCGTCGAAAAAGGCAATAAAAATTTTTATCACGTTTCTTTTTCTTGAAA 
               
               
                   
                   
                 ATTTTTTTTTTTGATTTTTTTCTCTTTCGATGACCTCCCATTGATATTTAAGTTAATAAACG 
               
               
                   
                   
                 GTCTTCAATTTCTCAAGTTTCAGTTTCATTTTTCTTGTTCTATTACAACTTTTTTTACTTCT 
               
               
                   
                   
                 TGCTCATTAGAAAGAAAGCATAGCAATCTAATCTAAGTTTTAATTACAAAATGCTGGGAT 
               
               
                   
                   
                 TCCCAATGTTCAACCCAGCTACGCCTGATGTCTGGAAGATGAATACCCCTTACTTTCCA 
               
               
                   
                   
                 TTTGTTACACCGGGGTTATTTCCTGCCTCAGCACCCCCATCGCCCACCAACGTAGATG 
               
               
                   
                   
                 CCGAAGCTGCCAGTTCCCAACAGTCGGAAGCAAGCTATCTGGATAAGGAGAAAATTGT 
               
               
                   
                   
                 TCGAGGGCCACTTGATTATCTTCTCAAATCCCCTGGAAAAGACATTCGTCGGAAATTCA 
               
               
                   
                   
                 TTCACGCGTTCAATGAATGGCTGCGCATTCCTGAGGACAAGTTGAATATTATCACGGAA 
               
               
                   
                   
                 ATTGTTGGATTGCTTCACACGGCCTCCCTTCTAATCGACGATATTCAGGACAATTCCAA 
               
               
                   
                   
                 GCTTCGACGCGGCCTCCCAGTGGCCCATAGCATATTTGGTATTGCGCAGACAATTAAC 
               
               
                   
                   
                 TCTGCCAATTATGCGTACTTTCTAGCCCAGGAAAGGCTCCGCGAACTGAATCATCCTGA 
               
               
                   
                   
                 AGCGTACGAAATATACACAGAGGAACTGCTTCGTCTGCACCGCGGTCAAGGTATGGAC 
               
               
                   
                   
                 TTGTACTGGCGGGACTGCCTAACCTGTCCCACAGAGGAGGACTATATTGAGATGATCG 
               
               
                   
                   
                 CCAACAAGACTGGTGGCCTATTTCGACTGGCGATTAAGCTTATGCAGTTGGAAAGCAC 
               
               
                   
                   
                 TTTGTGCAGCAATGTCATTGAACTAGCAGACTTGTTGGGCGTGATCTTTTAGATTCGGG 
               
               
                   
                   
                 ATGATTACCAAAACTTACAGAGTGGACTATACGCCAAGAACAAGGGATTTTGCGAGGAT 
               
               
                   
                   
                 TTGACGGAGGGAAAATTTTCCTTTCTGATTATCCACAGTATTAACAGTAACCCGAACAAT 
               
               
                   
                   
                 CACCATCTGCTAAATATACTACGGCAGCGGAGCGAGGACGATTCGGTGAAGAAGTATG 
               
               
                   
                   
                 CTGTTGATTATATCGACTCGACGGGGAGTTTTGACTACTGCCGGGAACGGCTCGCTTC 
               
               
                   
                   
                 CTTATTGGAAGAGGCGGATCAAATGGTTAAGAAGTTGGAAAATGAGGGGGGACAATCA 
               
               
                   
                   
                 AAGGGGATCTACGATATTCTGAGCTTTCTGTCGTGAGCGGATCTCTTATGTCTTTACGA 
               
               
                   
                   
                 TTTATAGTTTTCATTATCAAGTATGCCTATATTAGTATATAGCATCTTTAGATGACAGTGT 
               
               
                   
                   
                 TCGAAGTTTCACGAATAAAAGATAATATTCTACTTTTTGCTCCCACCGCGTTTGCTAGCA 
               
               
                   
                   
                 CGAGTGAACACCATCCCTCGCCTGTGAGTTGTACCCATTCCTCTAAACTGTAGACATGG 
               
               
                   
                   
                 TAGCTTCAGCAGTGTTCGTTATGTACGGCATCCTCCAACAAACAGTCGGTTATAGTTTG 
               
               
                   
                   
                 TCCTGCTCCTCTGAATCGTCTCCCTCGATATTTCTCATTTTCCTTCGCATGCCAGCATTG 
               
               
                   
                   
                 AAATGATCGAAGTTCAATGATGAAACGGTAATTCTTCTGTCATTTACTCATCTCATCTCA 
               
               
                   
                   
                 TCAAGTTATATAATTCTATACGGATGTAATTTTTCACTTTTCGTCTTGACGTCCACCCTAT 
               
               
                   
                   
                 AATTTCAATTATTGAACCCTCACTGGGTCATTACGTAAATAATGATAGGAATGGGATTCT 
               
               
                   
                   
                 TCTATTTTTCCTTTTTCCATTCTAGCAGCCGTCGGGAAAACGTGGCATCCTCTCTTTCG 
               
               
                   
                   
                 GGCTCAATTGGAGTCACGCTGCCGTGAGCATCCTCTCTTTCCATATCTAACAACTGAGC 
               
               
                   
                   
                 ACGTAACCAATGGAAAAGCATGAGCTTAGCGTTGCTCCAAAAAAGTATTGGATGGTTAA 
               
               
                   
                   
                 TACCATTTGTCTGTTCTCTTCTGACTTTGACTCCTCAAAAAAAAAAAATCTACAATCAACA 
               
               
                   
                   
                 GATCGCTTCAATTACGCCCTCACAAAAACTTTTTTCCTTCTTCTTCGCCCACGTTAAATT 
               
               
                   
                   
                 TTATCCCTCATGTTGTCTAACGGATTTCTGCACTTGATTTATTATAAAAAGACAAAGACA 
               
               
                   
                   
                 TAATACTTCTCTATCAATTTCAGTTATTGTTCTTCCTTGCGTTATTCTTCTGTTCTTCTTTT 
               
               
                   
                   
                 TCTTTTGTCATATATAACCATAACCAAGTAATACATATTCAAAATGGATGGGTTCGACCA 
               
               
                   
                   
                 TTCTACTGCTCCACCAGGATATAACGAGCTAAAATGGCTCGCCGATATCTTCGTCATCG 
               
               
                   
                   
                 GAATGGCTGTTGGCTGGGTTGCTCACTATATGGAGATGATTCACACGTCGTTCAAGGA 
               
               
                   
                   
                 CCAAACATACTGCATGACCATCGGGGGCCTTTGCATCAATTTTGCCTGGGAAATCATAT 
               
               
                   
                   
                 TCTGCACAATGTATCCTGCCAAAGGATTTGTCGAGCGGGTTGCCTTTCTCATGGGCATT 
               
               
                   
                   
                 TCTCTCGACCTTGGGGTTATTTACGCGGGAATCAAGAACGCCCCAAATGAATGGCACC 
               
               
                   
                   
                 ACTCTGCAATGGTGAGGGACCATATGCCCCTTGTCTTCGCAGCAACGACACTTTGTTGT 
               
               
                   
                   
                 CTGAGCGGTCATATGGCTCTTACTGCCCAGGTTGGTCCCGCACAAGCCTATACGTGGG 
               
               
                   
                   
                 GGGCAATTGCATGCCAGCTCTTTATCAGCATAGGGAATGTGTTTCAATTGTTGAGTCGG 
               
               
                   
                   
                 GGAAACACACGAGGGGCGTCATGGACGCTATGGACCTCCAGGTTTTTTGGATCAACAT 
               
               
                   
                   
                 CAGCCATTGGCTTTGCTCTTGTTCGATATATTCGCTGGTGGGAGGCCTTTTCTTGGTTG 
               
               
                   
                   
                 AACTGCCCGCTTGTGATATGGTCCGTGGCCATGTTCTTTCTGTTTGAAACACTCTATGG 
               
               
                   
                   
                 AGCCCTATTCTATTCTGTCAAGCGACAAGAAGGGAGATCCCAGCGTGGAATCAAGCAC 
               
               
                   
                   
                 AAAGAGAGGTAGACAAATCGCTCTTAAATATATACCTAAAGAACATTAAAGCTATATTAT 
               
               
                   
                   
                 AAGCAAAGATACGTAAATTTTGCTTATATTATTATACACATATCATATTTCTATATTTTTAA 
               
               
                   
                   
                 GATTTGGTTATATAATGTACGTAATGCAAAGGAAATAAATTTTATACATTATTGAACAGC 
               
               
                   
                   
                 GTCCAAGTAACTACATTATGTGCACTAATAGTTTAGCGTCGTGAAGACTTTATTGTGTCG 
               
               
                   
                   
                 CGAAAAGTAAAAATTTTAAAAATTAGAGCACCTTGAACTTGCGAAAAAGGTTCTCATCAA 
               
               
                   
                   
                 CTGTTTAAAAGGAGGATATCAGGTCCTATTTCTGACAAACAATATACAAATTTAGTTTCA 
               
               
                   
                   
                 AAGATGAATCAGTGCGCGAAGGACATAACTCAACAGTTTATTCCTGGCATCCACTAAAT 
               
               
                   
                   
                 ATAATGGAGCCCGCTTTTTAAGCTGGCATCCAGAAAAAAAAAGAATCCCAGCACCAAAA 
               
               
                   
                   
                 TATTGTTTTCTTCACCAACCATCAGTTCATAGGTCCATTCTCTTAGCGCAACTACAGAGA 
               
               
                   
                   
                 ACAGGGGCACAAACAGGCAAAAAACGGGCACAACCTCAATGGAGTGATGCAACCTGC 
               
               
                   
                   
                 CTGGAGTAAATGATGACACAAGGCAATTGACCCACGCATGTATCTATCTCATTTTCTTA 
               
               
                   
                   
                 CACCTTCTATTACCTTCTGCTCTCTCTGATTTGGAAAAAGCTGAAAAAAAAGGTTGAAAC 
               
               
                   
                   
                 CAGTTCCCTGAAATTATTCCCCTACTTGACTAATAAGTATATAAAGACGGTAGGTATTGA 
               
               
                   
                   
                 TTGTAATTCTGTAAATCTATTTCTTAAACTTCTTAAATTCTACTTTTATAGTTAGTCTTTTT 
               
               
                   
                   
                 TTTAGTTTTAAAACACCAAGAACTTAGTTTCGAATAAACACACATAAACAAACAAAATGG 
               
               
                   
                   
                 CGGCACTTCCGGACGTTGCCTCCATTCCCATCCCTCTGGTGGCAACCCTAGGCATTGC 
               
               
                   
                   
                 CCCTCTAATTTTCTATCTCGTCCTTGATAGAATTAGCCCCTTGTGGCCAAATTCCAAAGC 
               
               
                   
                   
                 TTTCCTGATTGGCAAGAAGAAACCGGAGACCGTGACATCGTTCGAGTGCCCATATGCC 
               
               
                   
                   
                 TACATCCGTCAGATCTATGGGAAGTATCACTGGGAGCCATTCGTACAGAAGCTGTCTC 
               
               
                   
                   
                 CGAGGCTTAAGGATGAGGATCCGGCCAAATATAAGATGGTTCTGGAGATAATGGATGC 
               
               
                   
                   
                 AATCCACCTGTGTCTGATGCTAGTTGACGATATAACTGACAATAGCGACTATCGAAAAG 
               
               
                   
                   
                 GCAAGCCAGCAGCCCACCGGATATATGGCCCTTCAGAGACAGCAAATCGCGCTTACTA 
               
               
                   
                   
                 CCGAGTCACCCAGATTCTAAACAAGACCGTGCAAAAGTTCCCCAAGCTGGCCAAGTTC 
               
               
                   
                   
                 CTGCTTCAGAATCTGGAAGAAATTCTCGAAGGCCAAGACCTGTCACTAATCTGGCGAC 
               
               
                   
                   
                 GGGATGGACTGGGTAGCCTTTCGACTGTTCCTGATGAGCGAGTTGCAGCCTATCGCAA 
               
               
                   
                   
                 GATGGCGTCATTGAAAACTGGGGCGTTATTCCGGCTGCTGGGGCAATTGGTGATGGA 
               
               
                   
                   
                 GGACCAATCGATGGACGGGACGATGACTACTCTTGCGTGGTGCTCTCAGCTGCAGAAT 
               
               
                   
                   
                 GACTGCAAGAATGTCTACTCATCTGAATATGCTAAGGCCAAAGGGGCGCTTGCCGAAG 
               
               
                   
                   
                 ACCTCCGAAATCGAGAGCTCTCATTTCCAATTATCCTCGCGCTGGAAGCTCCTGAAGG 
               
               
                   
                   
                 GCATTGGGTCGCCAGTGCTTTGGAGACCAGCTCACCGCGCAACATTCGCAAGGCGCT 
               
               
                   
                   
                 TGCTGTGATTCAGAGTGAGAGAGTGCGCAATGCTTGTTTCAAGGAGCTCAAGTCGGCG 
               
               
                   
                   
                 AGTGCTTCGGTCCAGGACTGGTTGGCTATTTGGGGACGGAACGAGAAAATGAACTTGA 
               
               
                   
                   
                 AGAGCCAGCAGACGTAGAGTGCTTTTAACTAAGAATTATTAGTCTTTTCTGCTTATTTTT 
               
               
                   
                   
                 TCATCATAGTTTAGAACACTTTATATTAACGAATAGTTTATGAATCTATTTAGGTTTAAAA 
               
               
                   
                   
                 ATTGATACAGTTTTATAAGTTACTTTTTCAAAGACTCGTGCTGTCTATTGCATAATGCACT 
               
               
                   
                   
                 GGAAGGGGAAAAAAAAGGTGCACACGCGTGGCTTTTTCTTGAATTTGCAGTTTGAAAAA 
               
               
                   
                   
                 TAACTACATGGATGATAAGAAAACATGGAGTACAGTCACTTTGAGAACCTTCAATCAGC 
               
               
                   
                   
                 TGGTAACGTCTTCGTTAATTGGATACTCAAAAAAGATGGATAGCATGAATCACAAGATG 
               
               
                   
                   
                 GAAGGAAATGCGGGCCACGACCACAGTGATATGCATATGGGAGATGGAGATGATACCT 
               
               
                   
                   
                 TATATCTAGGAACCCATCAGGTTGGTGGAAGATTACCCGTTCTAAGACTTTTCAGCTTC 
               
               
                   
                   
                 CTCTATTGATGTTACACCTGGACACCCCTTTTCTGGCATCCAGTTTTTAATCTTCAGTGG 
               
               
                   
                   
                 CATGTGAGATTCTCCGAAATTAATTAAAGCAATCACATTCTCTCGGATACCACCTC 
               
               
                   
                   
                 GGTTGAAACTGACAGGTGGTFTGTTACGCATGCTAATGCAAAGGAGCCTATATACCTTT 
               
               
                   
                   
                 GGCTCGGCTGCTGTAACAGGGAATATAAAGGGCAGCATAATTTAGGAGTTTAGTGAAC 
               
               
                   
                   
                 TTGCAACATTTACTATTTTCCCTTCTTACGTAAATATTTTTCTTTTTAATTCTAAATCAATC 
               
               
                   
                   
                 TTTTTCAATTTTTTGTTTGTATTCTTTTCTTGCTTAAATCTATAACTACAAAAAACACATAC 
               
               
                   
                   
                 ATAAACTAAAAATGGCCAATGCCCAGCAACCCCCCTTTCGCATCCTTATTGTGGGCGGT 
               
               
                   
                   
                 TCTGTCGCAGGCCTCATCCTTGCGCACTGTCTCGAACGCGCCAATATAGAGTACCTCA 
               
               
                   
                   
                 TACTCGAAAAAGGAGAAGATGTTGCTCCACAAGTTGGTGCCTCGATAGGTATCATGCC 
               
               
                   
                   
                 AAATGGCGGACGGATCCTCGAGCAACTGGGCCTATTTGGGGAGATTGAGCGTGTGAT 
               
               
                   
                   
                 CGAGCCGTTGCATCAGGCGAATATCAGCTATCCAGATGGGTTCTGCTTTAGTAACGTCT 
               
               
                   
                   
                 ATCCTAAGGTTCTTGGCGACAGGTTCGGATACCCGGTTGCATTCTTGGACCGGCAGAA 
               
               
                   
                   
                 GTTCCTGCAGATTGCATATGAGGGGCTGAGAAAGAAGCAGAATGTTCTCACCGGTAAA 
               
               
                   
                   
                 AGGGTAGTTGGACTGCGACAGTCGGATCAAGGGACTGCTGTTTCTGTGGCTGACGGG 
               
               
                   
                   
                 ACAGAGTATGAGGCGGATCTCGTGGTTGGTGCTGATGGAGTACATAGTCGGGTGAGAA 
               
               
                   
                   
                 GTGAGATTTGGAAGATGGCGGAAGAGAATCAGCCTGCATCAGTTTCGACACGTGAAAG 
               
               
                   
                   
                 AAGAAGCATGACTGTTGAATATGTCTGCGTTTTCGGGATTTCATCAGCCATCCCAGGGC 
               
               
                   
                   
                 TCGAGATAAGCGAACAGATCAACGGTATTTTCGACCATCTATCCATTCTAACAATCCAT 
               
               
                   
                   
                 GGCAGACATGGTCGCGTGTTCTGGTTCGTGATCCAGAAGCTGGATAGGAAGTACGTCT 
               
               
                   
                   
                 ATCCTGATGTCCCGCGATTCTCAGACGAGGATGCCGTACAGCTCTTCGATCGGGTCAA 
               
               
                   
                   
                 ACACGTGCGGTTCTGGAAAAACATCTGTGTGGGGGACTTGTGGAAGAACAGAGAGGT 
               
               
                   
                   
                 GTCCTCGATGACAGCGCTGGAGGAGGGAGTGTTCGAGACATGGCATCATGATAGGAT 
               
               
                   
                   
                 GGTTTTGATTGGAGATAGCGTTCACAAGATGACGCCCAACTTTGGCCAAGGAGCTAATT 
               
               
                   
                   
                 CAGCCATCGAGGATGCTGCCGCGCTCTCTTCCCTTCTACATGATCTCGTCAACGCCCG 
               
               
                   
                   
                 TGGAGTTTGCAAGCCATCGAATGTCCAGATTCAGCATCTCCTCAAGCAGTATCGGGAG 
               
               
                   
                   
                 ACCCGATACACTCGCATGGTAGGCATGTGTCGCACCGCGGCTTCAGTCTCTCGGATTC 
               
               
                   
                   
                 AGGCCCGAGATGGCATCCTCAACACCGTCTTTGGACGATATTGGGCACCTTATGCTGG 
               
               
                   
                   
                 CAACCTGCCTGCTGACCTGGCATCAAAAGTGATGGCAGATGCAGAGGTTGTTACTTTT 
               
               
                   
                   
                 CTGCCCTTGCCAGGGCGCTCAGGACCGGGCTGGGAGATGTACAGACGAAAGGGGAA 
               
               
                   
                   
                 GGGAGGGCAGGTGCAATGGGTGCTTATAATCTTAAGCTTACTTACGATTGGTGGATTG 
               
               
                   
                   
                 TGCATCTGGCTACAAAGCAATGCGTTGAGTAGATAAGGAGATTGATAAGACTTTTCTAG 
               
               
                   
                   
                 TTGCATATCTTTTATATTTAAATCTTATCTATTAGTTAATTTTTTGTAATTTATCCTTATATA 
               
               
                   
                   
                 TAGTCTGGTTATTCTAAAATATCATTTCAGTATCTAAAAATTCCCCTCTTTTTTCAGTTAT 
               
               
                   
                   
                 ATCTTAACAGGCGACAGTCCAAATGTTGATTTATCCCAGTCCGATTCATCAGGGTTGTG 
               
               
                   
                   
                 AAGCATTTTGTCAATGGTCGAAATCACATCAGTAATAGTGCCTCTTACTTGCCTCATAGA 
               
               
                   
                   
                 ATTTCTTTCTCTTAACGTCACCGTTTGGTCTTTTATAGTTTCGAAATCTATGGTGATACCA 
               
               
                   
                   
                 AATGGTGTTCCCAATTCATCGTTACGGGCGTATTTTTTACCAATTGAAGTATTGGAATCG 
               
               
                   
                   
                 TCAATTTTAAAGTATATCTCTCTTTTACGTAAAGCCTGCGAGATCCTCTTAAGTATAGCG 
               
               
                   
                   
                 GGGAAGCCATCGTTATTCGATATTGTCGTAACAAATACTTTGATCGGCGCTATGCGGCC 
               
               
                   
                   
                 GCCACCGCGGTGGAGCTCCAGCTTTTGTTCCCTTTAGTGAGGGTTAATTGCGCGCTTG 
               
               
                   
                   
                 GCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACA 
               
               
                   
                   
                 CAACATAGGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGGTAA 
               
               
                   
                   
                 CTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCC 
               
               
                   
                   
                 AGCTGCATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCT 
               
               
                   
                   
                 CTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGG 
               
               
                   
                   
                 TATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGG 
               
               
                   
                   
                 AAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTT 
               
               
                   
                   
                 GCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCA 
               
               
                   
                   
                 AGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAA 
               
               
                   
                   
                 GCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTT 
               
               
                   
                   
                 TCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCG 
               
               
                   
                   
                 GTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGAC 
               
               
                   
                   
                 CGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTAT 
               
               
                   
                   
                 CGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTG 
               
               
                   
                   
                 CTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGGACAGTATTTGGT 
               
               
                   
                   
                 ATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCG 
               
               
                   
                   
                 GCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCG 
               
               
                   
                   
                 CAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGT 
               
               
                   
                   
                 GGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACC 
               
               
                   
                   
                 TAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTT 
               
               
                   
                   
                 GGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTT 
               
               
                   
                   
                 CGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATACGGGAGGGCT 
               
               
                   
                   
                 TACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCTCCAG 
               
               
                   
                   
                 ATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAA 
               
               
                   
                   
                 CTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCG 
               
               
                   
                   
                 CCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTC 
               
               
                   
                   
                 GTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGAT 
               
               
                   
                   
                 CCCCCATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAG 
               
               
                   
                   
                 TAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTG 
               
               
                   
                   
                 TCATGCCATCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGA 
               
               
                   
                   
                 GAATAGTGTATGCGGCGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCG 
               
               
                   
                   
                 CGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAA 
               
               
                   
                   
                 CTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAA 
               
               
                   
                   
                 CTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGC 
               
               
                   
                   
                 AAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCATACTCTTC 
               
               
                   
                   
                 CTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTT 
               
               
                   
                   
                 GAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCC 
               
               
                   
                   
                 ACCTGAACGAAGCATCTGTGCTTCATTTTGTAGAACAAAAATGCAACGCGAGAGCGCTA 
               
               
                   
                   
                 ATTTTTCAAACAAAGAATCTGAGCTGCATTTTTACAGAACAGAAATGCAACGCGAAAGC 
               
               
                   
                   
                 GCTATTTTACCAACGAAGAATCTGTGCTTCATTTTTGTAAAACAAAAATGCAACGCGAGA 
               
               
                   
                   
                 GCGCTAATTTTTCAAACAAAGAATCTGAGCTGCATTTTTACAGAACAGAAATGCAACGC 
               
               
                   
                   
                 GAGAGCGCTATTTTACCAACAAAGAATCTATACTTCTTTTTTGTTCTACAAAAATGCATC 
               
               
                   
                   
                 CCGAGAGCGCTATTTTTCTAACAAAGCATCTTAGATTACTTTTTTTCTCCTTTGTGCGCT 
               
               
                   
                   
                 CTATAATGCAGTCTCTTGATAACTTTTTGCACTGTAGGTCCGTTAAGGTTAGAAGAAGG 
               
               
                   
                   
                 CTACTTTGGTGTCTATTTTCTCTTCCATAAAAAAAGCCTGACTCCACTTCCCGCGTTTAC 
               
               
                   
                   
                 TGATTACTAGCGAAGCTGCGGGTGCATTTTTTCAAGATAAAGGCATCCCCGATTATATT 
               
               
                   
                   
                 CTATACCGATGTGGATTGCGCATACTTTGTGAACAGAAAGTGATAGCGTTGATGATTCT 
               
               
                   
                   
                 TCATTGGTCAGAAAATTATGAACGGTTTCTTCTATTTTGTCTCTATATACTACGTATAGG 
               
               
                   
                   
                 AAATGTTTACATTTTCGTATTGTTTTCGATTCACTCTATGAATAGTTCTTACTACAATTTTT 
               
               
                   
                   
                 TTGTCTAAAGAGTAATACTAGAGATAAACATAAAAAATGTAGAGGTCGAGTTTAGATGC 
               
               
                   
                   
                 AAGTTCAAGGAGCGAAAGGTGGATGGGTAGGTTATATAGGGATATAGCACAGAGATAT 
               
               
                   
                   
                 ATAGCAAAGAGATACTTTTGAGCAATGTTTGTGGAAGCGGTATTCGCAATATTTTAGTA 
               
               
                   
                   
                 GCTCGTTACAGTCCGGTGCGTTTTTGGTTTTTTGAAAGTGCGTCTTCAGAGCGCTTTTG 
               
               
                   
                   
                 GTTTTCAAAAGCGCTCTGAAGTTCCTATACTTTCTAGAGAATAGGAACTTCGGAATAGG 
               
               
                   
                   
                 AACTTCAAAGCGTTTCCGAAAACGAGCGCTTCCGAAAATGCAACGCGAGCTGCGCACA 
               
               
                   
                   
                 TACAGCTCACTGTTCACGTCGCACCTATATCTGCGTGTTGCCTGTATATATATATACATG 
               
               
                   
                   
                 AGAAGAACGGCATAGTGCGTGTTTATGCTTAAATGCGTACTTATATGCGTCTATTTATGT 
               
               
                   
                   
                 AGGATGAAAGGTAGTCTTAGTACCTCCTGTGATATTATCCCATTCCATGCGGGGTATCGT 
               
               
                   
                   
                 ATGCTTCCTTCAGCACTACCCTTTAGCTGTTCTATATGCTGCCACTCCTCAATTGGATTA 
               
               
                   
                   
                 GTCTCATCCTTCAATGCTATCATTTCCTTTGATATTGGATCATACTAAGAAACCATTATTA 
               
               
                   
                   
                 TCATGACATTAACCTATAAAAATAGGCGTATCACGAGGCCCTTTCGTCTCGCGCGTTTC 
               
               
                   
                   
                 GGTGATGACGGTGAAAACCTCTGACACATGCAGCTCCCGGAGACGGTCACAGCTTGTC 
               
               
                   
                   
                 TGTAAGCGGATGCCGGGAGCAGACAAGCCCGTCAGGGCGCGTCAGCGGGTGTTGGC 
               
               
                   
                   
                 GGGTGTCGGGGCTGGCTTAACTATGCGGCATCAGAGCAGATTGTACTGAGAGTGCAC 
               
               
                   
                   
                 CATATCGACTACGTCGTAAGGCCGTTTCTGACAGAGTAAAATTCTTGAGGGAACTTTCA 
               
               
                   
                   
                 CCATTATGGGAAATGCTTCAAGAAGGTATTGACTTAAACTCCATCAAATGGTCAGGTCA 
               
               
                   
                   
                 TTGAGTGTTTTTTATTTGTTGTATTTTTTTTTTTTTAGAGAAAATCCTCCAATATCAAATTA 
               
               
                   
                   
                 GGAATCGTAGTTTCATGATTTTCTGTTACACCTAACTTTTTGTGTGGTGCCCTCCTCCTT 
               
               
                   
                   
                 GTCAATATTAATGTTAAAGTGCAATTCTTTTTCCTTATCACGTTGAGCCATTAGTATCAAT 
               
               
                   
                   
                 TTGCTTACCTGTATTCCTTTACTATCCTCCTTTTTCTCCTTCTTGATAAATGTATGTAGAT 
               
               
                   
                   
                 TGCGTATATAGTTTCGTCTACCCTATGAACATATTCCATTTTGTAATTTCGTGTCGTTTCT 
               
               
                   
                   
                 ATTATGAATTTCATTTATAAAGTTTATGTACAAATATCATAAAAAAAGAGAATCTTTTTAA 
               
               
                   
                   
                 GCAAGGATTTTCTTAACTTCTTCGGCGACAGCATCACCGACTTCGGTGGTACTGTTGGA 
               
               
                   
                   
                 ACCACCTAAATCACCAGTTCTGATACCTGCATCCAAAACCTTTTTAACTGCATCTTCAAT 
               
               
                   
                   
                 GGCCTTACCTTCTTCAGGCAAGTTCAATGACAATTTCAACATCATTGCAGCAGACAAGA 
               
               
                   
                   
                 TAGTGGCGATAGGGTCAACCTTATTCTTTGGCAAATCTGGAGCAGAACCGTGGCATGG 
               
               
                   
                   
                 TTCGTACAAACCAAATGCGGTGTTCTTGTCTGGCAAAGAGGCCAAGGACGCAGATGGC 
               
               
                   
                   
                 AACAAACCCAAGGAACCTGGGATAACGGAGGCTTCATCGGAGATGATATCACCAAACA 
               
               
                   
                   
                 TGTTGCTGGTGATTATAATACCATTTAGGTGGGTTGGGTTCTTAACTAGGATCATGGCG 
               
               
                   
                   
                 GCAGAATCAATCAATTGATGTTGAACCTTCAATGTAGGGAATTCGTTCTTGATGGTTTCC 
               
               
                   
                   
                 TCCACAGTTTTTCTCCATAATCTTGAAGAGGCCAAAAGATTAGCTTTATCCAAGGACCAA 
               
               
                   
                   
                 ATAGGCAATGGTGGCTCATGTTGTAGGGCCATGAAAGCGGCCATTCTTGTGATTCTTTG 
               
               
                   
                   
                 CACTTCTGGAACGGTGTATTGTTCACTATCCCAAGCGACACCATCACCATCGTCTTCCT 
               
               
                   
                   
                 TTCTCTTACCAAAGTAAATACCTCCCACTAATTCTCTGACAACAACGAAGTCAGTACCTT 
               
               
                   
                   
                 TAGCAAATTGTGGCTTGATTGGAGATAAGTCTAAAAGAGAGTCGGATGCAAAGTTACAT 
               
               
                   
                   
                 GGTCTTAAGTTGGCGTACAATTGAAGTTCTTTACGGATTTTTAGTAAACCTTGTTCAGGT 
               
               
                   
                   
                 CTAACACTACCGGTACCCCATTTAGGACCAGCCACAGCACCTAACAAAACGGCATCAA 
               
               
                   
                   
                 CCTTCTTGGAGGCTTCCAGCGCCTCATCTGGAAGTGGGACACCTGTAGCATCGATAGC 
               
               
                   
                   
                 AGCACCACCAATTAAATGATTTTCGAAATCGAACTTGACATTGGAACGAACATCAGAAA 
               
               
                   
                   
                 TAGCTTTAAGAACCTTAATGGCTTCGGCTGTGATTTCTTGACCAACGTGGTCACCTGGC 
               
               
                   
                   
                 AAAACGACGATCTTCTTAGGGGCAGACATAGGGGCAGACATTAGAATGGTATATCCTT 
               
               
                   
                   
                 GAAATATATATATATATTGCTGAAATGTAAAAGGTAAGAAAAGTTAGAAAGTAAGACGAT 
               
               
                   
                   
                 TGCTAACCACCTATTGGAAAAAACAATAGGTCCTTAAATAATATTGTCAACTTCAAGTAT 
               
               
                   
                   
                 TGTGATGCAAGCATTTAGTCATGAACGCTTCTTCTATTCTTATATGAAAAGCCGGTTCCGG 
               
               
                   
                   
                 CCTCTCACCTTTCCTTTTTCTCCCAATTTTTCAGTTGAAAAAGGTATATGCGTCAGGCGA 
               
               
                   
                   
                 CCTCTGAAATTAACAAAAAATTTCCAGTCATCGAATTTGATTCTGTGCGATAGCGCCCCT 
               
               
                   
                   
                 GTGTGTTCTCGTTATGTTGAGGAAAAAAATAATGGTTGCTAAGAGATTCGAACTCTTGC 
               
               
                   
                   
                 ATCTTACGATACCTGAGTATTCCCACAGTTAACTGCGGTCAAGATATTTCTTGAATCAG 
               
               
                   
                   
                 GCGCCTTAGACCGCTCGGCCAAACAACCAATTACTTGTTGAGAAATAGAGTATAATTAT 
               
               
                   
                   
                 CCTATAAATATAACGTTTTTGAACACACATGAACAAGGAAGTACAGGACAATTGATTTTG 
               
               
                   
                   
                 AAGAGAATGTGGATTTTGATGTAATTGTTGGGATTCCATTTTTAATAAGGCAATAATATT 
               
               
                   
                   
                 AGGTATGTGGATATACTAGAAGTTCTCCTCGACCGTCGATATGCGGTGTGAAATACCG 
               
               
                   
                   
                 CACAGATGCGTAAGGAGAAAATACCGCATCAGGAAATTGTAAACGTTAATATTTTGTTA 
               
               
                   
                   
                 AAATTCGCGTTAAATTTTTGTTAAATCAGCTCATTTTTTAACCAATAGGCCGAAATCGGC 
               
               
                   
                   
                 AAAATCCCTTATAAATCAAAAGAATAGACCGAGATAGGGTTGAGTGTTGTTCCAGTTTG 
               
               
                   
                   
                 GAACAAGAGTCCACTATTAAAGAACGTGGACTCCAACGTCAAAGGGCGAAAAACCGTC 
               
               
                   
                   
                 TATCAGGGCGATGGCCCACTACGTGAACCATCACCCTAATCAAGTTTTTTGGGGTCGA 
               
               
                   
                   
                 GGTGCCGTAAAGCACTAAATCGGAACCCTAAAGGGAGCCCCCGATTTAGAGCTTGACG 
               
               
                   
                   
                 GGGAAAGCCGGCGAACGTGGCGAGAAAGGAAGGGAAGAAAGCGAAAGGAGCGGGCG 
               
               
                   
                   
                 CTAGGGCGCTGGCAAGTGTAGCGGTCACGCTGCGCGTAACCACCACACCCGCCGCGC 
               
               
                   
                   
                 TTAATGCGCCGCTACAGGGCGCGTCGCGCCATTCGCCATTCAGGCTGCGCAACTGTT 
               
               
                   
                   
                 GGGAAGGGCGATCGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGAT 
               
               
                   
                   
                 GTGCTGCAAGGCGATTAAGTTGGGTAACGCCAGGGTTTTCCCAGTCACGACGTTGTAA 
               
               
                   
                   
                 AACGACGGCCAGTGAGCGCGCGTAATACGACTCACTATAGGGCGAATTGGGTACCGG 
               
               
                   
                   
                 GCCCCCCCTCGAGGTCGACGGTATCGATAAGCTTGATATCGAATTCCTGCAGCCCGGG 
               
               
                   
                   
                 GGATCCACTAGTTCTAGATTAATTAA 
               
               
                   
               
            
           
         
       
     
     Doctrine of Equivalents 
     While the above description contains many specific embodiments of the invention, these should not be construed as limitations on the scope of the invention, but rather as an example of one embodiment thereof. Accordingly, the scope of the invention should be determined not by the embodiments illustrated, but by the appended claims and their equivalents.