Patent Publication Number: US-2022220454-A1

Title: Thermostable glucose oxidase

Description:
TECHNICAL FIELD 
     The present invention belongs to the field of protein engineering, and specifically relates to a glucose oxidase derived from filamentous fungi, especially an  Aspergillus niger  glucose oxidase. The thermal stability of the  Aspergillus niger  glucose oxidase is improved after modification by introducing disulfide bonds. 
     BACKGROUND 
     A glucose oxidase (GOD, E.C 1.1.3.4) is an aerobic dehydrogenase, its enzyme molecule is a dimer containing two subunits and having a molecular weight of about 160 kDa, and each subunit is combined with an FAD molecule. The glucose oxidase can be used for specifically catalyzing β-D-glucose to produce gluconic acid and hydrogen peroxide by using molecular oxygen as an electron acceptor. GOD is widely distributed in animals, plants and microorganisms, but there are certain limitations in extracting GOD from animal and plant tissues, the enzyme production is not high, and the GOD production of bacteria is also low. A microbial fermentation method is a main method for producing GOD. At present, most of commercial products on the market are produced by fermenting  Pichia pastoris  and filamentous fungi, such as  Aspergillus niger  and  Aspergillus oryzae.    
     Due to the advantages of catalytic specificity and high efficiency, GOD is widely used in the fields of food, chemical engineering, medicine, agriculture and feeds and has received more and more attention in recent years, and market demands are also increasing. Due to the effects of deoxidation and oxidation resistance, GOD is widely used in the fields of food, medicine and feeds. As a food preservative in the food industry, GOD has significant effects in preventing aging of beers, maintaining original flavors of products and prolonging the shelf life and can also be used as a flour improver and a bread quality improver to improve food quality. In the medical field, a GOD electrode method and a GOD-peroxidase coupling method are commonly used to detect the content of glucose in blood and serum. As a new feed additive, GOD can improve intestinal environments of animals, so that the feed utilization rate is increased, and the growth of the animals is promoted. Since GOD is widely used in various fields, higher and higher requirements are put forward for existing performance of the GOD in industry, especially the feed industry. For example, the enzyme activity is not reduced at room temperature for a long time, and the GOD has resistance to heat, extreme pH conditions and digestive enzymes. The thermal stability is very important in application of GOD, and GOD with high heat resistance has higher advantages in preparation of GOD under extreme reaction conditions (high temperature). Therefore, improvement of the thermal stability of GOD has an important practical significance in wide promotion and application of the GOD. 
     SUMMARY 
     The inventor found that the stability can be improved by introducing one or more pairs of disulfide bonds to specific positions in an amino acid sequence of a wild-type  Aspergillus niger  glucose oxidase (for example, those having sequence identity higher than 80% with a wild-type  Aspergillus niger  glucose oxidase set forth in SEQ ID NO: 1) or a mutant  Aspergillus niger  glucose oxidase (for example, those having sequence identity higher than 75% with a mutant  Aspergillus niger  glucose oxidase set forth in SEQ ID NO: 8 or SEQ ID NO: 10). 
     In some embodiments, one or more pairs of disulfide bonds shown in Table 1 are introduced to specific positions in an amino acid sequence of a mutant  Aspergillus niger  glucose oxidase having sequence identity higher than 80% with the wild-type  Aspergillus niger  glucose oxidase set forth in SEQ ID NO: 1. In some preferred embodiments, one or more pairs of disulfide bonds shown in Table 1 are introduced to specific positions in an amino acid sequence of an  Aspergillus niger  glucose oxidase having sequence identity higher than 85%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% with the wild-type  Aspergillus niger  glucose oxidase set forth in SEQ ID NO: 1. 
     In other embodiments, one or more pairs of disulfide bonds shown in Table 1 are introduced to specific positions in an amino acid sequence of a mutant  Aspergillus niger  glucose oxidase having sequence identity higher than 75% with the mutant  Aspergillus niger  glucose oxidase set forth in SEQ ID NO: 8 or SEQ ID NO: 10. In some preferred embodiments, one or more pairs of disulfide bonds shown in Table 1 are introduced to specific positions in an amino acid sequence of a mutant  Aspergillus niger  glucose oxidase having sequence identity higher than 78%, 79%, 80%, 82%, 84%, 86%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% with the mutant  Aspergillus niger  glucose oxidase set forth in SEQ ID NO: 8 or SEQ ID NO: 10. 
     Specifically, the inventor found that the thermal stability can be improved by separately introducing one pair or a combination of more pairs of disulfide bonds in Table 1 one or more pairs of disulfide bonds shown in Table 1 are introduced the  Aspergillus niger  glucose oxidase mutant set forth in SEQ ID NO: 8 or SEQ ID NO: 10. 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 Names and positions of introduced disulfide bonds (the  
               
               
                 amino acid position number is based on SEQ ID NO: 1) 
               
            
           
           
               
               
               
            
               
                   
                 Names of disulfide bonds 
                 Positions of disulfide bonds 
               
               
                   
                   
               
               
                   
                 A 
                 S53/T246 
               
               
                   
                 B 
                 A25/V250 
               
               
                   
                 C 
                 V20/S45 
               
               
                   
                 D 
                 T39/L242 
               
               
                   
                 E 
                 T87/P508 
               
               
                   
                   
               
            
           
         
       
     
     In order to achieve an objective of the present invention, “introduction” does not limit formation of the disulfide bonds to any particular way. For example, “introduction” of the disulfide bonds may include replacing an amino acid residue at a corresponding position in a glucose oxidase sequence into which the disulfide bonds are to be introduced with an amino acid residue capable of forming disulfide bonds (including, for example, a cysteine residue Cys, a homocysteine residue Hcy, and the like) and/or inserting an amino acid residue capable of forming disulfide bonds at a corresponding position. Such substitution and/or insertion may be achieved, for example, by using a site-directed mutagenesis method known in the art. “Introduction” also includes the situation that any one or two amino acid residues forming the disulfide bonds are produced by natural mutation. In order to produce such modified mutants, microbial bacteria such as  Escherichia coli , fungi such as yeast ( Pichia pastoris, Schizosaccharomyces pombe  and the like), filamentous fungi (such as  Aspergillus niger, Aspergillus oryzae  and  Trichoderma reesei ) and plants (such as corn, soybeans and wheat) can be used as hosts for expression. 
     In order to construct the mutants above, a conventional site-directed mutagenesis method can be used on the basis of a wild-type nucleic acid sequence, and a gene synthesis method can also be used for synthesizing the mutants from zero. A promoter and a terminator are ligated, introduced into a host cell and then expressed under suitable culture conditions. The methods above are conventional methods in the art. 
     Based on this discovery, this application provides the following technical solutions. 
     An objective of the present invention is to provide a thermostable glucose oxidase, containing at least one pair of introduced disulfide bonds in an amino acid sequence of a wild-type  Aspergillus niger  glucose oxidase or a mutant  Aspergillus niger  glucose oxidase, where the amino acid sequence of the wild-type glucose oxidase is set forth in SEQ ID NO: 1; compared with the wild-type  Aspergillus niger  glucose oxidase set forth in SEQ ID NO: 1, the mutant  Aspergillus niger  glucose oxidase has mutants in at least one position; and the introduced disulfide bonds are selected from: 
     (A) disulfide bonds formed between an amino acid residue at a position corresponding position 53 of SEQ ID NO: 1 and an amino acid residue at a position corresponding to position 246 of SEQ ID NO: 1; 
     (B) disulfide bonds formed between an amino acid residue at a position corresponding position 25 of SEQ ID NO: 1 and an amino acid residue at a position corresponding to position 250 of SEQ ID NO: 1; 
     (C) disulfide bonds formed between an amino acid residue at a position corresponding position 20 of SEQ ID NO: 1 and an amino acid residue at a position corresponding to position 45 of SEQ ID NO: 1; 
     (D) disulfide bonds formed between an amino acid residue at a position corresponding to position 39 of SEQ ID NO: 1 and an amino acid residue at a position corresponding to position 242 of SEQ ID NO: 1; 
     (E) disulfide bonds formed between an amino acid residue at a position corresponding to position 87 of SEQ ID NO: 1 and an amino acid residue at a position corresponding to position 508 of SEQ ID NO: 1. 
     In some embodiments of the present invention, compared with the wild-type  Aspergillus niger  glucose oxidase set forth in SEQ ID NO: 1, the mutant  Aspergillus niger  glucose oxidase has mutants in at least one of the following positions: 14, 16, 25, 30, 34, 37, 43, 45, 53, 67, 84, 90, 92, 94, 96, 106, 121, 135, 141, 142, 162, 167, 204, 246, 259, 315, 332, 362, 405, 406, 420, 446, 449, 453, 477, 501, 504, 506, 509, 510, 521, 526, 528, 536, 554, 560, 572, 575 and 577. 
     In some embodiments of the present invention, compared with the wild-type  Aspergillus niger  glucose oxidase set forth in SEQ ID NO: 1, the mutant  Aspergillus niger  glucose oxidase has at least one of the following mutants: D14E, S16A, A25V, T30V, T34V, R37K, N43D, S45T, S53C, A67Y, E84C, Q90R, A92Q, I94V, S96F, V106I, S121A, N135S, L141K, Q142K, A162T, V167I, F204L, T246C, G259A, D315K, A332S, S362T, N405K, H406D, V420E, H446R, A449M, Q453N, S477Y, S501R, T504V, Y506W, Y509E, H510N, C521A, K526R, M528L, A536L, T554M, V560L, S572A, I575V and E577A. 
     In some embodiments of the present invention, compared with the wild-type  Aspergillus niger  glucose oxidase set forth in SEQ ID NO: 1, the mutant  Aspergillus niger  glucose oxidase has mutants in at least one of the following positions: 14, 16, 30, 34, 37, 43, 45, 53, 67, 84, 90, 94, 106, 135, 162, 167, 204, 246, 259, 315, 332, 362, 405, 406, 420, 446, 501, 504, 509, 510, 554, 572, 575 and 577. 
     In some embodiments of the present invention, compared with the wild-type  Aspergillus niger  glucose oxidase set forth in SEQ ID NO: 1, the mutant  Aspergillus niger  glucose oxidase has at least one of the following mutants: D14E, S16A, T30V, T34V, R37K, N43D, S45T, S53C, A67Y, E84C, Q90R, I94V, V106I, N135S, A162T, V167I, F204L, T246C, G259A, D315K, A332S, S362T, N405K, H406D, V420E, H446R, S501R, T504V, Y509E, H510N, T554M, 5572A, I575V and E577A. 
     In some embodiments of the present invention, compared with the wild-type  Aspergillus niger  glucose oxidase set forth in SEQ ID NO: 1, the mutant  Aspergillus niger  glucose oxidase has mutants in at least one of the following positions: 14, 30, 37, 43, 45, 53, 67, 84, 90, 94, 106, 135, 162, 167, 204, 246, 259, 315, 406, 420, 446, 501, 509, 572 and 577. 
     In some embodiments of the present invention, compared with the wild-type  Aspergillus niger  glucose oxidase set forth in SEQ ID NO: 1, the mutant  Aspergillus niger  glucose oxidase has at least one of the following mutants: D14E, T30V, R37K, N43D, S45T, S53C, A67Y, E84C, Q90R, I94V, V106I, N135S, A162T, V167I, F204L, T246C, G259A, D315K, H406D, V420E, H446R, S501R, Y509E, S572A and E577A. 
     In some embodiments of the present invention, compared with the wild-type  Aspergillus niger  glucose oxidase set forth in SEQ ID NO: 1, the mutant  Aspergillus niger  glucose oxidase has mutants in at least one of the following positions: 14, 30, 37, 43, 53, 67, 84, 90, 94, 106, 135, 162, 204, 246, 315, 446, 501, 509 and 554. 
     In some embodiments of the present invention, compared with the wild-type  Aspergillus niger  glucose oxidase set forth in SEQ ID NO: 1, the mutant  Aspergillus niger  glucose oxidase has at least one of the following mutants: D14E, T30V, R37K, N43D, S53C, A67Y, E84C, Q90R, I94V, V106I, N135S, A162T, F204L, T246C, D315K, H446R, S501R, Y509E and T554M. 
     In some embodiments of the present invention, the amino acid sequence of the mutant  Aspergillus niger  glucose oxidase is set forth in SEQ ID NO. 8 or SEQ ID NO. 10. 
     In some embodiments of the present invention, the amino acid sequence of the thermostable glucose oxidase satisfies at least one of the items (A), (B), (C) and (E). 
     In some embodiments of the present invention, the amino acid sequence of the thermostable glucose oxidase satisfies any two, three or all of the items (A), (B), (C) and (E). 
     In some embodiments of the present invention, the amino acid sequence of the thermostable glucose oxidase satisfies the item (A), (B) or (C). 
     In some embodiments of the present invention, the amino acid sequence of the thermostable glucose oxidase satisfies the item (A). 
     In some embodiments of the present invention, the amino acid sequence of the thermostable glucose oxidase satisfies the item (B). 
     In some embodiments of the present invention, the amino acid sequence of the thermostable glucose oxidase satisfies the item (C). 
     In some embodiments of the present invention, the thermostable glucose oxidase includes any amino acid sequence selected from the following group consisting of SEQ ID NOs: 11-15, 17, 19, 21 or 23. 
     In some embodiments of the present invention, the thermostable glucose oxidase is obtained by heterologous expression in a  Pichia pastoris  host. 
     In some embodiments of the present invention, the amino acid residue capable of forming the disulfide bonds is a cysteine residue or a homocysteine residue. 
     Another objective of the present invention is to provide a polynucleotide encoding the thermostable glucose oxidase. 
     In some embodiments of the present invention, a sequence of the polynucleotide encoding the thermostable glucose oxidase is codon-optimized for expression in  Pichia pastoris.    
     In some embodiments of the present invention, the polynucleotide includes a nucleotide sequence set forth in any one of SEQ ID NO: 3-7, 16, 18, 20 or 22. 
     Another objective of the present invention is to provide a host cell, which contains the polynucleotide encoding the thermostable glucose oxidase. 
     In some embodiments of the present invention, the host cell is a fungal cell, a bacterial cell or a plant cell. 
     In some embodiments of the present invention, the host cell is a yeast cell or a filamentous fungal cell. 
     In some embodiments of the present invention, the host cell is a  Pichia pastoris  cell or an  Aspergillus niger  cell. 
     A fourth objective of the present invention is to provide application of the thermostable glucose oxidase in the fields of food, chemical engineering, medicine, agriculture or feeds. 
     As used herein, A, R, C, Q, N, L, K, M, F, P, S, T, W, Y, V, G and E are abbreviations of alanine (Ala), arginine (Arg), cysteine (Cys), glutamine (Gln), asparagine (Asn), leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), proline (Pro), serine (Ser), threonine (Thr), tryptophan (Trp), tyrosine (Tyr), valine (Val), glycine (Gly) and glutamic acid (Glu) respectively. 
     As used herein, the term “glucose oxidase mutant”, “mutant” or “mutant glucose oxidase” refers to a polypeptide having glucose oxidase activity and comprising a change such as substitution, insertion and/or deletion of one or more (several) amino acid residues at one or more (several) positions. Substitution refers to replacing an amino acid at a certain position with a different amino acid; deletion refers to removing an amino acid at a certain position; insertion refers to adding 1-5 amino acids to a position adjacent to and behind an amino acid at a certain position. Mutation of the wild-type glucose oxidase also refers to substitution, insertion and/or deletion of an amino acid in at least one position compared with the wild-type glucose oxidase, and preferably refers to substitution of an amino acid in at least one position; for example, T30V refers to substitution of threonine at the position 30 in the wild-type glucose oxidase with valine. 
     As used herein, the term “thermal stability” means that certain enzyme activity of the glucose oxidase mutant of the present invention is still maintained at a specific temperature after a given period of time. When properties such as thermal stability are involved, the term “improved thermal stability” means that after a period of time, the enzyme activity of the glucose oxidase mutant is higher than that of other glucose oxidase mutants and/or wild-type glucose oxidases. 
     As used herein, the terms “polynucleotide” and “nucleic acid” can be used interchangeably and refer to a polymerization form of nucleotides including ribonucleotides or deoxyribonucleotides in any length. Such terms include but are not limited to single-stranded, double-stranded or triple-stranded DNA, genomic DNA, cDNA, RNA, DNA-RNA hybrids or polymers containing purines, pyrimidine bases or other naturally, chemically or biochemically modified, non-nature or derived nucleotide bases. 
     As used herein, the term “vector” refers to a polynucleotide construct designed to introduce nucleic acid into one or more cell types. The vector includes a cloning vector, an expression vector, a shuttle vector, a plasmid, a kit and the like. 
     As used herein, the term “gene” refers to a polynucleotide encoding a polypeptide, including regions before and after a coding region and an intervening sequence (an intron) located between individual coding segments (exons). 
     As used herein, the term “percent (%) sequence identity” is defined as the percentage of amino acid residues in a candidate sequence the same as amino acid residues in a specific peptide or polypeptide sequence after the sequences are compared, gaps are introduced when necessary to obtain the maximum percent sequence identity and any conservative substitutions are not taken as a part of the sequence identity. Sequence comparisons can be performed in various ways within the technical scope of the field to determine percent amino acid sequence identity. For example, publicly available computer software, such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software is used. Those skilled in the art can determine appropriate parameters for measuring comparison, including any algorithm required to obtain the maximum comparison over the full length of the compared sequences. 
     As used herein, the term “host cell” refers to a host suitable for an expression vector containing the DNA according to the present invention. 
     The present invention has the following beneficial effects: 
     In the present invention, one or more pairs of disulfide bonds are introduced into a wild-type glucose oxidase and treated at 70° C. for 3 minutes, and the thermal stability is significantly improved than that of the wild-type glucose oxidase. Preferably, the enzyme activity of the glucose oxidase mutant is improved by 70% or above. More preferably, the enzyme activity of the glucose oxidase mutant is improved by 120% or above. Particularly preferably, the enzyme activity of the glucose oxidase mutant is improved by 180%. In the present invention, one or more pairs of disulfide bonds are introduced into the glucose oxidase mutant and treated at 70° C. for 3 minutes, and the enzyme activity is improved by 34% or above than that of the mutant. After treatment at 80° C. for 3 minutes, the enzyme activity is greatly improved from zero. In the present invention, one or more pairs of disulfide bonds are introduced into a glucose oxidase mutant derived from other  Aspergillus niger  and treated at 80° C. for 3 minutes, and the enzyme activity is improved by 350% or above than that of the mutant and is significantly higher than that of the existing wild-type glucose oxidase. Therefore, according to the technical solutions of the present invention, the enzyme activity of the glucose oxidase can be improved. Especially, due to the thermal stability, the glucose oxidase is suitable for application in industrial production, for example, application in the fields of food, chemical engineering, medicine, agriculture, and feeds. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a pPIC9K-GOD-wt plasmid profile. 
         FIG. 2  is a diagram showing determination results of thermal stability of a wild-type glucose oxidase and disulfide bond mutants. 
     
    
    
     DETAILED DESCRIPTION 
     Technical solutions of the present invention are further described in detail below with reference to the specific examples. It should be noted that, the examples described herein are merely used for explaining the present invention, instead limiting the scope of the present invention. 
     Example 1 Construction of Disulfide Bond Mutants 
     The 3D structure of a wild-type  Aspergillus niger  glucose oxidase is published (see Wohlfahrt, G et al, (1999) Acta Crystallogr., Sect. D55: 969-977), a 3D structure file PDB ID 1CF3 is taken as a reference, and disulfide bonds shown in the following table are designed and introduced. 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 Names and positions of introduced disulfide bonds (the amino  
               
               
                 acid position number is based on SEQ ID NO: 1) 
               
            
           
           
               
               
               
            
               
                   
                 Names of disulfide bonds 
                 Positions of disulfide bonds 
               
               
                   
                   
               
               
                   
                 A 
                 S53C/T246C 
               
               
                   
                 B 
                 A25C/V250C 
               
               
                   
                 C 
                 V20C/S45C 
               
               
                   
                 D 
                 T39C/L242C 
               
               
                   
                 E 
                 T87C/P508C 
               
               
                   
                 F 
                 L9C/L245C 
               
               
                   
                 G 
                 G52C/G99C 
               
               
                   
                 H 
                 S56C/R230C 
               
               
                   
                 I 
                 S45C/N241C 
               
               
                   
                 J 
                 E63C/V224C 
               
               
                   
                 K 
                 Y182C/G346C 
               
               
                   
                 L 
                 G251C/P443C 
               
               
                   
                 M 
                 S191C/A479C 
               
               
                   
                   
               
            
           
         
       
     
     The amino acid sequence of the wild-type glucose oxidase was set forth in SEQ ID NO: 1, pPIC9K was used as an expression vector, a  Saccharomyces cerevisiae  Alpha factor was used as a signal peptide, a synthetic wild-type glucose oxidase gene sequence GOD-wt (the sequence contains EcoR I and Not I digestion sites at two ends) and pPIC9K were digested with EcoR I and Not I respectively and then ligated and transferred into  Escherichia coli  DH5 α competent cells, transformants were picked for sequencing verification, and a wild-type glucose oxidase expression plasmid pPIC9K-GOD-wt shown in  FIG. 1  was obtained. Mutant sequences were named GOD-A to GOD-M according to names of the disulfide bonds in the table above. A glucose oxidase gene GOD-wt (set forth in SEQ ID NO: 2) and the mutant sequences GOD-A to GOD-M were synthesized by using a whole gene synthesis method, the mutant sequences GOD-A to GOD-E were set forth in SEQ ID NO: 3 to SEQ ID NO: 7, and gene synthesis was completed by Nanjing GenScript Biotechnology Co., Ltd. The synthetic gene have EcoR I and Not I restriction sites at two ends. 
     In order to express the glucose oxidase and the mutants, operations were performed on  Pichia pastoris  GS115 and the plasmid with reference to instructions of a Pichia expression kit (Invitrogen). Specifically, after the  Pichia pastoris  GS115 strain was cultured on a YPD culture plate (1% yeast extract, 2% proteins, 2% glucose and 1.5% agar) at 30° C. for 48 hours, single clones were picked and cultured in 4 mL of a YPD liquid culture medium (1% yeast extract, 2% proteins, and 2% glucose) at 30° C. and 200 rpm for 12 hours and then transferred into a triangular flask containing 30 mL of a YPD liquid culture medium and cultured at 30° C. and 220 rpm for 4-5 hours, the culture solution was centrifuged at 4° C. and 9,000 rpm for 2 minutes after it was detected that the OD600 value was in a range of 1.1-1.3, 4 mL of bacterial cells were collected into a sterilized EP tube, a supernatant was slightly removed, the remaining supernatant was absorbed with sterilized filter paper, the bacterial cells were resuspended in 1 mL of precooled sterilized water and centrifuged at 4° C., and 9,000 rpm for 2 minutes, and the supernatant was removed. The steps above were repeated, the bacterial cells were resuspended in 1 mL of precooled sorbitol (1 mol/L) and centrifuged at 4° C. and 9,000 rpm for 2 minutes, the supernatant was removed, and the bacterial cells were resuspended in 100-150 μl of precooled sorbitol (1 mol/L) to prepare competent cells. The expression plasmid pPIC9K-GOD-wt and the remaining 13 disulfide bond mutants were linearized with PmeI, linearized fragments were purified, recovered and then transferred into the  Pichia pastoris  GS115 competent cells by using an electroporation method, a mixture was uniformly coated on an MDH plate and invert-cultured at 30° C. for 2-3 days, all colonies on the plate were washed off with sterile water and then coated on YPD plates (0.5-8 mg/mL) containing different concentrations of geneticin, and multi-copy transformants were screened. Recombinant  Pichia pastoris  strains screened on the MDH plate were named GOD-A, GOD-B, GOD-C, GOD-D, GOD-E, GOD-F, GOD-G, GOD-H, GOD-I, GOD-J, GOD-K, GOD-L and GOD-M. The clones obtained after screening were separately transferred into a BMGY culture medium and cultured in an oscillating shaker at 30° C. and 250 rpm for 24 hours, then transferred into a BMMY culture medium for induced expression at 30° C. and 250 rpm for 120 hours with addition of 0.5% methanol every day, and finally centrifuged at 9,000-12,000 rpm for 10 minutes to remove the bacterial cells, a fermentation supernatant containing the glucose oxidase GOD-wt and 13 mutants thereof was obtained, and SDS-PAGE results show that GOD-G, GOD-I, GOD-K and GOD-L mutants were not expressed and the remaining 9 mutants were all expressed. 
     Example 2 Detection of Enzyme Activity of Glucose Oxidase 
     Under aerobic conditions, dehydrogenation of glucose was catalyzed by GOD to produce H2O2, and under the action of a horseradish peroxidase (POD), an oxygen donor o-dianisidine (DH2) was oxidized to obtain a brown product. The activity of GOD can be calculated according to a change of an absorbance at 540 nm and a standard curve. An enzyme activity determination system containing 2.5 mL of an o-dianisidine solution, 0.3 mL of 18% glucose and 0.1 mL of a 90 U/mL horseradish peroxidase was kept at 35° C. for 2 minutes, 0.1 mL of a diluted enzyme solution sample was added into a test tube for reaction for 3 minutes, 2 mol/L sulfuric acid was added to stop the reaction, the test tube was taken out, an absorbance at OD540 was determined, and a heat-inactivated enzyme solution was used as a blank control. According to results of the standard curve, an activity unit of the glucose oxidase was calculated. 
     Reagents and Solutions 
     A 0.1 mol/L disodium hydrogen phosphate-sodium citrate buffer with a pH of 5.5: 14.32 g of disodium hydrogen phosphate and 8.4056 g of citric acid monohydrate were accurately weighed and dissolved in 400 ml of distilled water, the pH was adjusted to 5.5 with disodium hydrogen phosphate, and the buffer was obtained for later use. 
     An o-dianisidine solution: 0.1 g of o-dianisidine was accurately weighed and dissolved in 10 ml of methanol to obtain a stock solution with effective storage time of 3 days at 4° C. Before an experiment, 0.1 ml of the stock solution was taken and dissolved in 12 ml of the 0.1 mol/L phosphate buffer with a pH of 5.5 to obtain the o-dianisidine solution. 
     18% glucose: 9.0000 g of glucose (AR) dried to a constant weight was accurately weighed and dissolved in a small amount of distilled water, and the solution was made to 50 ml with distilled water and stored at 4° C. 
     2 mol/L H2SO4: 40.00 g of H2SO4 was accurately weighed and slowly added into 160 mL of distilled water, and the solution was made to 200 mL for later use. 
     A GOD standard product: a sigma glucose oxidase standard product with an enzyme activity of 10,000 units was purchased, 5 mL of distilled water was accurately added and mixed, and the solution was stored at −20° C. for later use. 
     A 90 U/mL horseradish peroxidase: a horseradish peroxidase standard product (enzyme activity &gt;250 units/mg, 100 mg) was purchased, 1 mL of distilled water was accurately added to fully dissolve the horseradish peroxidase, and the solution was stored at −20° C. for later use. An appropriate amount of the standard product was taken and diluted to an enzyme activity of 90 U/ml before use, and the standard product needs to be used immediately after dilution. 
     Determination of Enzyme Activity 
     (1) Drawing of a Standard Curve 
     GOD standard products were diluted to 0.4, 0.8, 1.2, 1.6, 2.0 and 2.4 U/mL respectively, 2.5 mL of the o-dianisidine solution, 0.3 mL of 18% glucose solution and 0.1 mL of the 90 U/mL horseradish peroxidase solution were added into a test tube and preheated at 35° C. for 2 minutes, 0.1 mL of the diluted GOD standard product was added at an interval of 15 seconds and accurately reacted for 3 minutes, then 2 ml of 2 mol/L H2SO4 was immediately added to stop the reaction, the mixture was taken out and mixed uniformly, an absorbance value at 540 nm was determined, and a standard curve y=Kx+b was drawn with the absorbance value as the abscissa and a standard enzyme activity as the ordinate. 
     (2) Determination of Samples 
     2.5 mL of the o-dianisidine solution, 0.3 mL of 18% glucose solution and 0.1 mL of the 90 U/mL horseradish peroxidase solution were added into a test tube and preheated at 35° C. for 2 minutes, 0.1 mL of a diluted to-be-detected sample (a dilution standard is that the detected absorbance of the sample was within a linear range) was added at an interval of 15 seconds and accurately subjected to a reaction for 3 minutes, 2 ml of 2 mol/L H2SO4 was immediately added to stop the reaction, the mixture was taken out and mixed uniformly, the absorbance value A at 540 nm was detected, and the enzyme activity was calculated. 
     (3) Calculation of Enzyme Activity 
         X =( K*A+b )* n    
     in the formula, 
     X represents an enzyme activity of a sample U/ml, A represents a determined absorbance value of the sample, 
     n represents a dilution multiple of an enzyme solution, K represents a slope of a standard curve, 
     and b represents an intercept of the standard curve. 
     Example 3 Determination of Thermal Stability of Glucose Oxidase and Mutants Thereof 
     The fermentation supernatant obtained in Example 1 was diluted to about 100 U/mL with distilled water and treated at 70° C. for 3 minutes, a residual enzyme activity was determined, and a relative enzyme activity was calculated with an enzyme activity of an untreated sample as 100%. Thermal stability data are shown in  FIG. 2  and the table below. The results show that introduction of disulfide bonds has significant influence on the mutants, the introduction of some disulfide bonds such as GOD-G, GOD-I, GOD-K and GOD-L causes that the mutants cannot be expressed normally, such as GOD-G, GOD-I, GOD-K and GOD-L. The introduction of some specific disulfide bonds such as GOD-F, GOD-H, GOD-J and GOD-M causes that the thermal stability of the mutants is lower than that of the wild-type glucose oxidase. In addition, the introduction of other disulfide bonds causes that the thermal stability of the mutants is significantly improved. For example, the thermal stability of GOD-A, GOD-B, GOD-C, GOD-D and GOD-E is significantly improved. Preferably, the residual enzyme activity of the glucose oxidase mutants is improved by 70% or above in comparison with that of the wild-type glucose oxidase. More preferably, the enzyme activity of the glucose oxidase mutants is improved by 120% or above. Particularly preferably, the enzyme activity of the glucose oxidase mutants is improved by 180%. The results above that the mutants with higher thermal stability can be obtained by introducing suitable disulfide bond combinations. 
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Results of residual enzyme activity at 70° C. 
               
            
           
           
               
               
               
               
            
               
                   
                 Names of  
                 Residual enzyme 
                 Improvement in comparison 
               
               
                   
                 mutants 
                 activity at 70° C. 
                 with wild type (%) 
               
               
                   
                   
               
               
                   
                 GOD-wt 
                 30% 
                 / 
               
               
                   
                 GOD-A 
                 84% 
                 180% 
               
               
                   
                 GOD-B 
                 51% 
                  70% 
               
               
                   
                 GOD-C 
                 68% 
                 126% 
               
               
                   
                 GOD-D 
                 51% 
                  70% 
               
               
                   
                 GOD-E 
                 54% 
                  80% 
               
               
                   
                 GOD-F 
                 10% 
                 / 
               
               
                   
                 GOD-H 
                  8% 
                 / 
               
               
                   
                 GOD-J 
                  4% 
                 / 
               
               
                   
                 GOD-M 
                 16% 
                 / 
               
               
                   
                   
               
            
           
         
       
     
     Example 4 
     As a heat-resistant excellent mutant obtained by mutation screening of a wild-type glucose oxidase (as described in US2016/0068824), F91 has 5 mutants introduced on the basis of a wild type thereof, and a specific sequence is set forth in SEQ ID NO: 8. In order to detect whether or not the disulfide bond mutants described in Example 1 can also achieve functions on the glucose oxidase mutant, and further improve the stability, disulfide bonds A and B were respectively introduced on the basis of a sequence F91 by using the method in Example 1 and named F19-A and F19-B, the two mutants were expressed by using  Pichia pastoris  and separately incubated at 70° C. and 80° C. for 3 minutes, and then thermal stability was determined by using the method in Example 3. The results are as shown in Table 2 that the thermal stability of the mutants is further improved by introducing the disulfide bonds A and B, improved by 34% and 35% at 70° C. in comparison with that of the mutant F91 respectively, and especially the thermal stability of the mutants at 80° C. is improved. F91 has no residual enzyme activity at 80° C., and residual enzyme activities after addition of the disulfide bonds can reach 12% and 7% respectively, realizing great improvement from zero. It can be seen that as proposed by the inventor, the thermal stability of the glucose oxidase mutant can be more effectively improved by introducing the disulfide bonds. 
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 Results of residual enzyme activity of F91 before and after  
               
               
                 introduction of disulfide bonds 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Residual 
                 Improvement in 
                   
                 Improvement in 
               
               
                 Names of 
                 enzyme activity 
                 comparison with the 
                 Residual enzyme 
                 comparison with the 
               
               
                 mutants 
                 at 70° C. 
                 mutant at 70° C. (%) 
                 activity at 80° C. 
                 mutant at 80° C. (%) 
               
               
                   
               
               
                 F91 
                 70% 
                 / 
                 0 
                 / 
               
               
                 F91-A 
                 94% 
                 34% 
                 12% 
                 — 
               
               
                 F91-B 
                 95% 
                 35% 
                  7% 
                 — 
               
               
                   
               
            
           
         
       
     
     Example 5 Determination of Thermal Stability of Glucose Oxidase Mutants Derived from Other  Aspergillus niger  after Introduction of Disulfide Bonds 
     A wild-type glucose oxidase sequence derived from other  Aspergillus niger  is set forth in SEQ ID NO: 9, and has a similarity of 97% with SEQ ID NO: 1. As a heat-resistant excellent mutant obtained by mutation screening of a wild-type glucose oxidase derived from other  Aspergillus niger  (as described in 108893453), GOD-M5 has 5 mutants introduced on the basis of the wild type, and a specific sequence is set forth in SEQ ID NO: 10. In order to detect whether or not the disulfide bond mutants described in Example 1 can also achieve functions on the glucose oxidase mutant derived from other  Aspergillus niger , and further improve the thermal stability, disulfide bonds A and B were respectively introduced on the basis of a sequence GOD-M5 by using the method in Example 1 and named GOD-M5-A and GOD-M5-B, the two mutants were expressed by using  Pichia pastoris  and separately incubated at 70° C. and 80° C. for 3 minutes, and then thermal stability was determined by using the method in Example 3. The results are as shown in Table 3 that the thermal stability of the mutants is further improved by introducing the disulfide bonds A and B, improved by 350% and 400% especially at 80° C. in comparison with that of the mutant GOD-M5 respectively. It can be seen that as proposed by the inventor, the thermal stability of the glucose oxidase mutant derived from different  Aspergillus niger  can be improved by introducing the disulfide bonds. 
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                 Results of residual enzyme activity of GOD-M5 before  
               
               
                 and after introduction of disulfide bonds 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                   
                   
                 Improvement  
               
               
                   
                 Residual 
                   
                 Residual 
                 in comparison  
               
               
                   
                 enzyme  
                 Improvement in 
                 enzyme 
                 with the 
               
               
                 Names of 
                 activity  
                 comparison with the 
                 activity  
                 mutant 
               
               
                 mutants 
                 at 70° C. 
                 mutant at 70° C. (%) 
                 at 80° C. 
                 at 80° C. (%) 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 GOD-M5 
                   94% 
                 / 
                  4% 
                 / 
               
               
                 GOD-M5-A 
                 97.8% 
                 4% 
                 18% 
                 350% 
               
               
                 GOD-M5-B 
                 96.3% 
                 2% 
                 20% 
                 400% 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
            
               
                   
                 GOD-wt 
               
               
                   
                 SEQ ID NO: 1 
               
               
                   
                 SNGIEASLLTDPKDVSGRTVDYTTAGGGLTGLTTA 
               
               
                   
               
               
                   
                 ARLTENPNISVLVIESGSYESDRGPIIEDLNAYGD 
               
               
                   
               
               
                   
                 IFGSSVDHAYETVELATNNQTALIRSGNGLGGSTL 
               
               
                   
               
               
                   
                 VNGGTWTRPHKAQVDSWETVFGNEGWNWDNVAAYS 
               
               
                   
               
               
                   
                 LQAERARAPNAKQIAAGHYFNASCHGVNGTVHAGP 
               
               
                   
               
               
                   
                 RDTGDDYSPIVKALMSAVEDRGVPTKKDFGCGDPH 
               
               
                   
               
               
                   
                 GVSMFPNTEHFDQVRSDAAREWLLPNYQRPNLQVL 
               
               
                   
               
               
                   
                 TGQYVGKVLLSQNGTTPRAVGVEFGTHKGNTIINV 
               
               
                   
               
               
                   
                 YAKIIEVLLAAGSAVSPTILEYSGIGMKSILEPLG 
               
               
                   
               
               
                   
                 IDTVVDLPVGLNLQDQTTATVRSRITSAGAGQGQA 
               
               
                   
               
               
                   
                 AWFATFNETFGDYSEKAHELLNTKLEQWAEEAVAR 
               
               
                   
               
               
                   
                 GGFHNTTALLIQYENYRDWIVNHNVAYSELFLDTA 
               
               
                   
               
               
                   
                 GV 
               
               
                   
               
               
                   
                 GOD-wt 
               
               
                   
                 SEQ ID NO: 2 
               
               
                   
                 GAATTCAGCAATGGCATTGAAGCCAGCCTCCTGAC 
               
               
                   
               
               
                   
                 TGATCCCAAGGATGTCTCCGGCCGCACGGTCGACT 
               
               
                   
               
               
                   
                 ACATCATCGCTGGTGGAGGTCTGACTGGACTCACC 
               
               
                   
               
               
                   
                 ACCGCTGCTCGTCTGACGGAGAACCCCAACATCAG 
               
               
                   
               
               
                   
                 TGTGCTCGTCATCGAAAGTGGCTCCTACGAGTCGG 
               
               
                   
               
               
                   
                 ACAGAGGTCCTATCATTGAGGACCTGAACGCCTAC 
               
               
                   
               
               
                   
                 GGCGACATCTTTGGCAGCAGTGTAGACCACGCCTA 
               
               
                   
               
               
                   
                 CGAGACCGTGGAGCTCGCTACCAACAATCAAACCG 
               
               
                   
               
               
                   
                 CGCTGATCCGCTCCGGAAATGGTCTCGGTGGCTCT 
               
               
                   
               
               
                   
                 ACTCTAGTGAATGGTGGCACCTGGACTCGCCCCCA 
               
               
                   
               
               
                   
                 CAAGGCACAGGTTGACTCTTGGGAGACTGTCTTTG 
               
               
                   
               
               
                   
                 GAAATGAGGGCTGGAACTGGGACAATGTGGCCGCC 
               
               
                   
               
               
                   
                 TACTCCCTCCAGGCTGAGCGTGCTCGCGCACCAAA 
               
               
                   
               
               
                   
                 TGCCAAACAGATCGCTGCTGGCCACTACTTCAACG 
               
               
                   
               
               
                   
                 CATCCTGCCATGGTGTTAATGGTACTGTCCATGCC 
               
               
                   
               
               
                   
                 GGACCCCGCGACACCGGCGATGACTATTCTCCCAT 
               
               
                   
               
               
                   
                 CGTCAAGGCTCTCATGAGCGCTGTCGAAGACCGGG 
               
               
                   
               
               
                   
                 GCGTTCCCACCAAGAAAGACTTCGGATGCGGTGAC 
               
               
                   
               
               
                   
                 CCCCATGGTGTGTCCATGTTCCCCAACACCTTGCA 
               
               
                   
               
               
                   
                 CGAAGACCAAGTGCGCTCCGATGCCGCTCGCGAAT 
               
               
                   
               
               
                   
                 GGCTACTTCCCAACTACCAACGTCCCAACCTGCAA 
               
               
                   
               
               
                   
                 GTCCTGACCGGACAGTATGTTGGTAAGGTGCTCCT 
               
               
                   
               
               
                   
                 TAGCCAGAACGGCACCACCCCTCGTGCCGTTGGCG 
               
               
                   
               
               
                   
                 TGGAATTCGGCACCCACAAGGGCAACACCCACAAC 
               
               
                   
               
               
                   
                 GTTTACGCTAAGCACGAGGTCCTCCTGGCCGCGGG 
               
               
                   
               
               
                   
                 CTCCGCTGTCTCTCCCACAATCCTCGAATATTCCG 
               
               
                   
               
               
                   
                 GTATCGGAATGAAGTCCATCCTGGAGCCCCTTGGT 
               
               
                   
               
               
                   
                 ATCGACACCGTCGTTGACCTGCCCGTCGGCTTGAA 
               
               
                   
               
               
                   
                 CCTGCAGGACCAGACCACCGCTACCGTCCGCTCCC 
               
               
                   
               
               
                   
                 GCATCACCTCTGCTGGTGCAGGACAGGGACAGGCC 
               
               
                   
               
               
                   
                 GCTTGGTTCGCCACCTTCAACGAGACCTTTGGTGA 
               
               
                   
               
               
                   
                 CTATTCCGAAAAGGCACACGAGCTGCTCAACACCA 
               
               
                   
               
               
                   
                 AGCTGGAGCAGTGGGCCGAAGAGGCCGTCGCCCGT 
               
               
                   
               
               
                   
                 GGCGGATTCCACAACACCACCGCCTTGCTCATCCA 
               
               
                   
               
               
                   
                 GTACGAGAACTACCGCGACTGGATTGTCAACCACA 
               
               
                   
               
               
                   
                 ACGTCGCGTACTCGGAACTCTTCCTCGACACTGCC 
               
               
                   
               
               
                   
                 GGAGTAGCCAGCTTCGATGTGTGGGACCTTCTGCC 
               
               
                   
               
               
                   
                 CTTCACCCGAGGATACGTTCACATCCTCGACAAGG 
               
               
                   
               
               
                   
                 ACCCCTACCTTCACCACTTCGCCTACGACCCTCAG 
               
               
                   
               
               
                   
                 TACTTCCTCAACGAGCTGGACCTGCTCGGTCAGGC 
               
               
                   
               
               
                   
                 TGCCGCTACTCAACTGGCCCGCAACATCTCCAACT 
               
               
                   
               
               
                   
                 CCGGTGCCATGCAGACCTACTTCGCTGGGGAGACT 
               
               
                   
               
               
                   
                 ATCCCCGGTGATAACCTCGCGTATGATGCCGATTT 
               
               
                   
               
               
                   
                 GAGCGCCTGGACTGAGTACATCCCGTACCACTTCC 
               
               
                   
               
               
                   
                 GTCCTAACTACCATGGCGTGGGTACTTGCTCCATG 
               
               
                   
               
               
                   
                 ATGCCGAAGGAGATGGGCGGTGTTGTTGATAATGC 
               
               
                   
               
               
                   
                 TGCCCGTGTGTATGGTGTGCAGGGACTGCGTGTCA 
               
               
                   
               
               
                   
                 TTGATGGTTCTATTCCTCCTACGCAAATGTCGTCC 
               
               
                   
               
               
                   
                 CATGTCATGACGGTGTTCTATGCCATGGCGCTAAA 
               
               
                   
               
               
                   
                 AATTTCGGATGCTATCTTGGAAGATTATGCTTCCA 
               
               
                   
               
               
                   
                 TGCAGTGAGAGGAAGA 
               
               
                   
               
               
                   
                 GOD-A 
               
               
                   
                 SEQ ID NO: 3 
               
               
                   
                 GAATTCAGCAATGGCATTGAAGCCAGCCTCCTGAC 
               
               
                   
               
               
                   
                 TGATCCCAAGGATGTCTCCGGCCGCACGGTCGACT 
               
               
                   
               
               
                   
                 ACATCATCGCTGGTGGAGGTCTGACTGGACTCACC 
               
               
                   
               
               
                   
                 ACCGCTGCTCGTCTGACGGAGAACCCCAACATCAG 
               
               
                   
               
               
                   
                 TGTGCTCGTCATCGAAAGTGGCTGCTACGAGTCGG 
               
               
                   
               
               
                   
                 ACAGAGGTCCTATCATTGAGGACCTGAACGCCTAC 
               
               
                   
               
               
                   
                 GGCGACATCTTTGGCAGCAGTGTAGACCACGCCTA 
               
               
                   
               
               
                   
                 CGAGACCGTGGAGCTCGCTACCAACAATCAAACCG 
               
               
                   
               
               
                   
                 CGCTGATCCGCTCCGGAAATGGTCTCGGTGGCTCT 
               
               
                   
               
               
                   
                 ACTCTAGTGAATGGTGGCACCTGGACTCGCCCCCA 
               
               
                   
               
               
                   
                 CAAGGCACAGGTTGACTCTTGGGAGACTGTCTTTG 
               
               
                   
               
               
                   
                 GAAATGAGGGCTGGAACTGGGACAATGTGGCCGCC 
               
               
                   
               
               
                   
                 TACTCCCTCCAGGCTGAGCGTGCTCGCGCACCAAA 
               
               
                   
               
               
                   
                 TGCCAAACAGATCGCTGCTGGCCACTACTTCAACG 
               
               
                   
               
               
                   
                 CATCCTGCCATGGTGTTAATGGTACTGTCCATGCC 
               
               
                   
               
               
                   
                 GGACCCCGCGACACCGGCGATGACTATTCTCCCAT 
               
               
                   
               
               
                   
                 CGTCAAGGCTCTCATGAGCGCTGTCGAAGACCGGG 
               
               
                   
               
               
                   
                 GCGTTCCCACCAAGAAAGACTTCGGATGCGGTGAC 
               
               
                   
               
               
                   
                 CCCCATGGTGTGTCCATGTTCCCCAACACCTTGCA 
               
               
                   
               
               
                   
                 CGAAGACCAAGTGCGCTCCGATGCCGCTCGCGAAT 
               
               
                   
               
               
                   
                 GGCTACTTCCCAACTACCAACGTCCCAACCTGCAA 
               
               
                   
               
               
                   
                 GTCCTGTGCGGACAGTATGTTGGTAAGGTGCTCCT 
               
               
                   
               
               
                   
                 TAGCCAGAACGGCACCACCCCTCGTGCCGTTGGCG 
               
               
                   
               
               
                   
                 TGGAATTCGGCACCCACAAGGGCAACACCCACAAC 
               
               
                   
               
               
                   
                 GTTTACGCTAAGCACGAGGTCCTCCTGGCCGCGGG 
               
               
                   
               
               
                   
                 CTCCGCTGTCTCTCCCACAATCCTCGAATATTCCG 
               
               
                   
               
               
                   
                 GTATCGGAATGAAGTCCATCCTGGAGCCCCTTGGT 
               
               
                   
               
               
                   
                 ATCGACACCGTCGTTGACCTGCCCGTCGGCTTGAA 
               
               
                   
               
               
                   
                 CCTGCAGGACCAGACCACCGCTACCGTCCGCTCCC 
               
               
                   
               
               
                   
                 GCATCACCTCTGCTGGTGCAGGACAGGGACAGGCC 
               
               
                   
               
               
                   
                 GCTTGGTTCGCCACCTTCAACGAGACCTTTGGTGA 
               
               
                   
               
               
                   
                 CTATTCCGAAAAGGCACACGAGCTGCTCAACACCA 
               
               
                   
               
               
                   
                 AGCTGGAGCAGTGGGCCGAAGAGGCCGTCGCCCGT 
               
               
                   
               
               
                   
                 GGCGGATTCCACAACACCACCGCCTTGCTCATCCA 
               
               
                   
               
               
                   
                 GTACGAGAACTACCGCGACTGGATTGTCAACCACA 
               
               
                   
               
               
                   
                 ACGTCGCGTACTCGGAACTCTTCCTCGACACTGCC 
               
               
                   
               
               
                   
                 GGAGTAGCCAGCTTCGATGTGTGGGACCTTCTGCC 
               
               
                   
               
               
                   
                 CTTCACCCGAGGATACGTTCACATCGCGACAAGGA 
               
               
                   
               
               
                   
                 CCCCTACCTTCACCACTTCGCCTACGACCCTCAGT 
               
               
                   
               
               
                   
                 ACTTCCTCAACGAGCTGGACCTGCTCGGTCAGGCT 
               
               
                   
               
               
                   
                 GCCGCTACTCAACTGGCCCGCAACATCTCCAACTC 
               
               
                   
               
               
                   
                 CGGTGCCATGCAGACCTACTTCGCTGGGGAGACTA 
               
               
                   
               
               
                   
                 TCCCCGGTGATAACCTCGCGTATGATGCCGATTTG 
               
               
                   
               
               
                   
                 AGCGCCTGGACTGAGTACATCCCGTACCACTTCCG 
               
               
                   
               
               
                   
                 TCCTAACTACCATGGCGTGGGTACTTGCTCCATGA 
               
               
                   
               
               
                   
                 TGCCGAAGGAGATGGGCGGTGTTGTTGATAATGCT 
               
               
                   
               
               
                   
                 GCCCGTGTGTATGGTGTGCAGGGACTGCGTGTCAT 
               
               
                   
               
               
                   
                 TGATGGTTCTATTCCTCCTACGCAAATGTCGTCCC 
               
               
                   
               
               
                   
                 ATGTCATGACGGTGTTCTATGCCATGGCGCTAAAA 
               
               
                   
               
               
                   
                 ATTTCGGATGCTATCTTGGAAGATTATGCTTCCAT 
               
               
                   
               
               
                   
                 GCAGTGAGAGGAAGA 
               
               
                   
               
               
                   
                 GOD-B 
               
               
                   
                 SEQ ID NO: 4 
               
               
                   
                 GAATTCAGCAATGGCATTGAAGCCAGCCTCCTGAC 
               
               
                   
               
               
                   
                 TGATCCCAAGGATGTCTCCGGCCGCACGGTCGACT 
               
               
                   
               
               
                   
                 ACATCATCTGCGGTGGAGGTCTGACTGGACTCACC 
               
               
                   
               
               
                   
                 ACCGCTGCTCGTCTGACGGAGAACCCCAACATCAG 
               
               
                   
               
               
                   
                 TGTGCTCGTCATCGAAAGTGGCTCCTACGAGTCGG 
               
               
                   
               
               
                   
                 ACAGAGGTCCTATCATTGAGGACCTGAACGCCTAC 
               
               
                   
               
               
                   
                 GGCGACATCTTTGGCAGCAGTGTAGACCACGCCTA 
               
               
                   
               
               
                   
                 CGAGACCGTGGAGCTCGCTACCAACAATCAAACCG 
               
               
                   
               
               
                   
                 CGCTGATCCGCTCCGGAAATGGTCTCGGTGGCTCT 
               
               
                   
               
               
                   
                 ACTCTAGTGAATGGTGGCACCTGGACTCGCCCCCA 
               
               
                   
               
               
                   
                 CAAGGCACAGGTTGACTCTTGGGAGACTGTCTTTG 
               
               
                   
               
               
                   
                 GAAATGAGGGCTGGAACTGGGACAATGTGGCCGCC 
               
               
                   
               
               
                   
                 TACTCCCTCCAGGCTGAGCGTGCTCGCGCACCAAA 
               
               
                   
               
               
                   
                 TGCCAAACAGATCGCTGCTGGCCACTACTTCAACG 
               
               
                   
               
               
                   
                 CATCCTGCCATGGTGTTAATGGTACTGTCCATGCC 
               
               
                   
               
               
                   
                 GGACCCCGCGACACCGGCGATGACTATTCTCCCAT 
               
               
                   
               
               
                   
                 CGTCAAGGCTCTCATGAGCGCTGTCGAAGACCGGG 
               
               
                   
               
               
                   
                 GCGTTCCCACCAAGAAAGACTTCGGATGCGGTGAC 
               
               
                   
               
               
                   
                 CCCCATGGTGTGTCCATGTTCCCCAACACCTTGCA 
               
               
                   
               
               
                   
                 CGAAGACCAAGTGCGCTCCGATGCCGCTCGCGAAT 
               
               
                   
               
               
                   
                 GGCTACTTCCCAACTACCAACGTCCCAACCTGCAA 
               
               
                   
               
               
                   
                 GTCCTGACCGGACAGTATTGCGGTAAGGTGCTCCT 
               
               
                   
               
               
                   
                 TAGCCAGAACGGCACCACCCCTCGTGCCGTTGGCG 
               
               
                   
               
               
                   
                 TGGAATTCGGCACCCACAAGGGCAACACCCACAAC 
               
               
                   
               
               
                   
                 GTTTACGCTAAGCACGAGGTCCTCCTGGCCGCGGG 
               
               
                   
               
               
                   
                 CTCCGCTGTCTCTCCCACAATCCTCGAATATTCCG 
               
               
                   
               
               
                   
                 GTATCGGAATGAAGTCCATCCTGGAGCCCCTTGGT 
               
               
                   
               
               
                   
                 ATCGACACCGTCGTTGACCTGCCCGTCGGCTTGAA 
               
               
                   
               
               
                   
                 CCTGCAGGACCAGACCACCGCTACCGTCCGCTCCC 
               
               
                   
               
               
                   
                 GCATCACCTCTGCTGGTGCAGGACAGGGACAGGCC 
               
               
                   
               
               
                   
                 GCTTGGTTCGCCACCTTCAACGAGACCTTTGGTGA 
               
               
                   
               
               
                   
                 CTATTCCGAAAAGGCACACGAGCTGCTCAACACCA 
               
               
                   
               
               
                   
                 AGCTGGAGCAGTGGGCCGAAGAGGCCGTCGCCCGT 
               
               
                   
               
               
                   
                 GGCGGATTCCACAACACCACCGCCTTGCTCATCCA 
               
               
                   
               
               
                   
                 GTACGAGAACTACCGCGACTGGATTGTCAACCACA 
               
               
                   
               
               
                   
                 ACGTCGCGTACTCGGAACTCTTCCTCGACACTGCC 
               
               
                   
               
               
                   
                 GGAGTAGCCAGCTTCGATGTGTGGGACCTTCTGCC 
               
               
                   
               
               
                   
                 CTTCACCCGAGGATACGTTCACATCCTCGACAAGG 
               
               
                   
               
               
                   
                 ACCCCTACCTTCACCACTTCGCCTACGACCCTCAG 
               
               
                   
               
               
                   
                 TACTTCCTCAACGAGCTGGACCTGCTCGGTCAGGC 
               
               
                   
               
               
                   
                 TGCCGCTACTCAACTGGCCCGCAACATCTCCAACT 
               
               
                   
               
               
                   
                 CCGGTGCCATGCAGACCTACTTCGCTGGGGAGACT 
               
               
                   
               
               
                   
                 ATCCCCGGTGATAACCTCGCGTATGATGCCGATTT 
               
               
                   
               
               
                   
                 GAGCGCCTGGACTGAGTACATCCCGTACCACTTCC 
               
               
                   
               
               
                   
                 GTCCTAACTACCATGGCGTGGGTACTTGCTCCATG 
               
               
                   
               
               
                   
                 ATGCCGAAGGAGATGGGCGGTGTTGTTGATAATGC 
               
               
                   
               
               
                   
                 TGCCCGTGTGTATGGTGTGCAGGGACTGCGTGTCA 
               
               
                   
               
               
                   
                 TTGATGGTTCTATTCCTCCTACGCAAATGTCGTCC 
               
               
                   
               
               
                   
                 CATGTCATGACGGTGTTCTATGCCATGGCGCTAAA 
               
               
                   
               
               
                   
                 AATTTCGGATGCTATCTTGGAAGATTATGCTTCCA 
               
               
                   
               
               
                   
                 TGCAGTGAGAGGAAGA 
               
               
                   
               
               
                   
                 GOD-C 
               
               
                   
                 SEQ ID NO: 5 
               
               
                   
                 GAATTCAGCAATGGCATTGAAGCCAGCCTCCTGAC 
               
               
                   
               
               
                   
                 TGATCCCAAGGATGTCTCCGGCCGCACGTGCGACT 
               
               
                   
               
               
                   
                 ACATCATCGCTGGTGGAGGTCTGACTGGACTCACC 
               
               
                   
               
               
                   
                 ACCGCTGCTCGTCTGACGGAGAACCCCAACATCTG 
               
               
                   
               
               
                   
                 CGTGCTCGTCATCGAAAGTGGCTCCTACGAGTCGG 
               
               
                   
               
               
                   
                 ACAGAGGTCCTATCATTGAGGACCTGAACGCCTAC 
               
               
                   
               
               
                   
                 GGCGACATCTTTGGCAGCAGTGTAGACCACGCCTA 
               
               
                   
               
               
                   
                 CGAGACCGTGGAGCTCGCTACCAACAATCAAACCG 
               
               
                   
               
               
                   
                 CGCTGATCCGCTCCGGAAATGGTCTCGGTGGCTCT 
               
               
                   
               
               
                   
                 ACTCTAGTGAATGGTGGCACCTGGACTCGCCCCCA 
               
               
                   
               
               
                   
                 CAAGGCACAGGTTGACTCTTGGGAGACTGTCTTTG 
               
               
                   
               
               
                   
                 GAAATGAGGGCTGGAACTGGGACAATGTGGCCGCC 
               
               
                   
               
               
                   
                 TACTCCCTCCAGGCTGAGCGTGCTCGCGCACCAAA 
               
               
                   
               
               
                   
                 TGCCAAACAGATCGCTGCTGGCCACTACTTCAACG 
               
               
                   
               
               
                   
                 CATCCTGCCATGGTGTTAATGGTACTGTCCATGCC 
               
               
                   
               
               
                   
                 GGACCCCGCGACACCGGCGATGACTATTCTCCCAT 
               
               
                   
               
               
                   
                 CGTCAAGGCTCTCATGAGCGCTGTCGAAGACCGGG 
               
               
                   
               
               
                   
                 GCGTTCCCACCAAGAAAGACTTCGGATGCGGTGAC 
               
               
                   
               
               
                   
                 CCCCATGGTGTGTCCATGTTCCCCAACACCTTGCA 
               
               
                   
               
               
                   
                 CGAAGACCAAGTGCGCTCCGATGCCGCTCGCGAAT 
               
               
                   
               
               
                   
                 GGCTACTTCCCAACTACCAACGTCCCAACCTGCAA 
               
               
                   
               
               
                   
                 GTCCTGACCGGACAGTATGTTGGTAAGGTGCTCCT 
               
               
                   
               
               
                   
                 TAGCCAGAACGGCACCACCCCTCGTGCCGTTGGCG 
               
               
                   
               
               
                   
                 TGGAATTCGGCACCCACAAGGGCAACACCCACAAC 
               
               
                   
               
               
                   
                 GTTTACGCTAAGCACGAGGTCCTCCTGGCCGCGGG 
               
               
                   
               
               
                   
                 CTCCGCTGTCTCTCCCACAATCCTCGAATATTCCG 
               
               
                   
               
               
                   
                 GTATCGGAATGAAGTCCATCCTGGAGCCCCTTGGT 
               
               
                   
               
               
                   
                 ATCGACACCGTCGTTGACCTGCCCGTCGGCTTGAA 
               
               
                   
               
               
                   
                 CCTGCAGGACCAGACCACCGCTACCGTCCGCTCCC 
               
               
                   
               
               
                   
                 GCATCACCTCTGCTGGTGCAGGACAGGGACAGGCC 
               
               
                   
               
               
                   
                 GCTTGGTTCGCCACCTTCAACGAGACCTTTGGTGA 
               
               
                   
               
               
                   
                 CTATTCCGAAAAGGCACACGAGCTGCTCAACACCA 
               
               
                   
               
               
                   
                 AGCTGGAGCAGTGGGCCGAAGAGGCCGTCGCCCGT 
               
               
                   
               
               
                   
                 GGCGGATTCCACAACACCACCGCCTTGCTCATCCA 
               
               
                   
               
               
                   
                 GTACGAGAACTACCGCGACTGGATTGTCAACCACA 
               
               
                   
               
               
                   
                 ACGTCGCGTACTCGGAACTCTTCCTCGACACTGCC 
               
               
                   
               
               
                   
                 GGAGTAGCCAGCTTCGATGTGTGGGACCTTCTGCC 
               
               
                   
               
               
                   
                 CTTCACCCGAGGATACGTTCACATCCTCGACAAGG 
               
               
                   
               
               
                   
                 ACCCCTACCTTCACCACTTCGCCTACGACCCTCAG 
               
               
                   
               
               
                   
                 TACTTCCTCAACGAGCTGGACCTGCTCGGTCAGGC 
               
               
                   
               
               
                   
                 TGCCGCTACTCAACTGGCCCGCAACATCTCCAACT 
               
               
                   
               
               
                   
                 CCGGTGCCATGCAGACCTACTTCGCTGGGGAGACT 
               
               
                   
               
               
                   
                 ATCCCCGGTGATAACCTCGCGTATGATGCCGATTT 
               
               
                   
               
               
                   
                 GAGCGCCTGGACTGAGTACATCCCGTACCACTTCC 
               
               
                   
               
               
                   
                 GTCCTAACTACCATGGCGTGGGTACTTGCTCCATG 
               
               
                   
               
               
                   
                 ATGCCGAAGGAGATGGGCGGTGTTGTTGATAATGC 
               
               
                   
               
               
                   
                 TGCCCGTGTGTATGGTGTGCAGGGACTGCGTGTCA 
               
               
                   
               
               
                   
                 TTGATGGTTCTATTCCTCCTACGCAAATGTCGTCC 
               
               
                   
               
               
                   
                 CATGTCATGACGGTGTTCTATGCCATGGCGCTAAA 
               
               
                   
               
               
                   
                 AAATTTCGGATGCTATCTTGGAAGATTATGCTTCC 
               
               
                   
               
               
                   
                 ATGCAGTGAGAGGAAGA 
               
               
                   
               
               
                   
                 GOD-D 
               
               
                   
                 SEQ ID NO: 6 
               
               
                   
                 GAATTCAGCAATGGCATTGAAGCCAGCCTCCTGAC 
               
               
                   
               
               
                   
                 TGATCCCAAGGATGTCTCCGGCCGCACGGTCGACT 
               
               
                   
               
               
                   
                 ACATCATCGCTGGTGGAGGTCTGACTGGACTCACC 
               
               
                   
               
               
                   
                 ACCGCTGCTCGTCTGTGCGAGAACCCCAACATCAG 
               
               
                   
               
               
                   
                 TGTGCTCGTCATCGAAAGTGGCTCCTACGAGTCGG 
               
               
                   
               
               
                   
                 ACAGAGGTCCTATCATTGAGGACCTGAACGCCTAC 
               
               
                   
               
               
                   
                 GGCGACATCTTTGGCAGCAGTGTAGACCACGCCTA 
               
               
                   
               
               
                   
                 CGAGACCGTGGAGCTCGCTACCAACAATCAAACCG 
               
               
                   
               
               
                   
                 CGCTGATCCGCTCCGGAAATGGTCTCGGTGGCTCT 
               
               
                   
               
               
                   
                 ACTCTAGTGAATGGTGGCACCTGGACTCGCCCCCA 
               
               
                   
               
               
                   
                 CAAGGCACAGGTTGACTCTTGGGAGACTGTCTTTG 
               
               
                   
               
               
                   
                 GAAATGAGGGCTGGAACTGGGACAATGTGGCCGCC 
               
               
                   
               
               
                   
                 TACTCCCTCCAGGCTGAGCGTGCTCGCGCACCAAA 
               
               
                   
               
               
                   
                 TGCCAAACAGATCGCTGCTGGCCACTACTTCAACG 
               
               
                   
               
               
                   
                 CATCCTGCCATGGTGTTAATGGTACTGTCCATGCC 
               
               
                   
               
               
                   
                 GGACCCCGCGACACCGGCGATGACTATTCTCCCAT 
               
               
                   
               
               
                   
                 CGTCAAGGCTCTCATGAGCGCTGTCGAAGACCGGG 
               
               
                   
               
               
                   
                 GCGTTCCCACCAAGAAAGACTTCGGATGCGGTGAC 
               
               
                   
               
               
                   
                 CCCCATGGTGTGTCCATGTTCCCCAACACCTTGCA 
               
               
                   
               
               
                   
                 CGAAGACCAAGTGCGCTCCGATGCCGCTCGCGAAT 
               
               
                   
               
               
                   
                 GGCTACTTCCCAACTACCAACGTCCCAACTGCCAA 
               
               
                   
               
               
                   
                 GTCCTGACCGGACAGTATGTTGGTAAGGTGCTCCT 
               
               
                   
               
               
                   
                 TAGCCAGAACGGCACCACCCCTCGTGCCGTTGGCG 
               
               
                   
               
               
                   
                 TGGAATTCGGCACCCACAAGGGCAACACCCACAAC 
               
               
                   
               
               
                   
                 GTTTACGCTAAGCACGAGGTCCTCCTGGCCGCGGG 
               
               
                   
               
               
                   
                 CTCCGCTGTCTCTCCCACAATCCTCGAATATTCCG 
               
               
                   
               
               
                   
                 GTATCGGAATGAAGTCCATCCTGGAGCCCCTTGGT 
               
               
                   
               
               
                   
                 ATCGACACCGTCGTTGACCTGCCCGTCGGCTTGAA 
               
               
                   
               
               
                   
                 CCTGCAGGACCAGACCACCGCTACCGTCCGCTCCC 
               
               
                   
               
               
                   
                 GCATCACCTCTGCTGGTGCAGGACAGGGACAGGCC 
               
               
                   
               
               
                   
                 GCTTGGTTCGCCACCTTCAACGAGACCTTTGGTGA 
               
               
                   
               
               
                   
                 CTATTCCGAAAAGGCACACGAGCTGCTCAACACCA 
               
               
                   
               
               
                   
                 AGCTGGAGCAGTGGGCCGAAGAGGCCGTCGCCCGT 
               
               
                   
               
               
                   
                 GGCGGATTCCACAACACCACCGCCTTGCTCATCCA 
               
               
                   
               
               
                   
                 GTACGAGAACTACCGCGACTGGATTGTCAACCACA 
               
               
                   
               
               
                   
                 ACGTCGCGTACTCGGAACTCTTCCTCGACACTGCC 
               
               
                   
               
               
                   
                 GGAGTAGCCAGCTTCGATGTGTGGGACCTTCTGCC 
               
               
                   
               
               
                   
                 CTTCACCCGAGGATACGTTCACATCCTCGACAAGG 
               
               
                   
               
               
                   
                 ACCCCTACCTTCACCACTTCGCCTACGACCCTCAG 
               
               
                   
               
               
                   
                 TACTTCCTCAACGAGCTGGACCTGCTCGGTCAGGC 
               
               
                   
               
               
                   
                 TGCCGCTACTCAACTGGCCCGCAACATCTCCAACT 
               
               
                   
               
               
                   
                 CCGGTGCCATGCAGACCTACTTCGCTGGGGAGACT 
               
               
                   
               
               
                   
                 ATCCCCGGTGATAACCTCGCGTATGATGCCGATTT 
               
               
                   
               
               
                   
                 GAGCGCCTGGACTGAGTACATCCCGTACCACTTCC 
               
               
                   
               
               
                   
                 GTCCTAACTACCATGGCGTGGGTACTTGCTCCATG 
               
               
                   
               
               
                   
                 ATGCCGAAGGAGATGGGCGGTGTTGTTGATAATGC 
               
               
                   
               
               
                   
                 TGCCCGTGTGTATGGTGTGCAGGGACTGCGTGTCA 
               
               
                   
               
               
                   
                 TTGATGGTTCTATTCCTCCTACGCAAATGTCGTCC 
               
               
                   
               
               
                   
                 CATGTCATGACGGTGTTCTATGCCATGGCGCTAAA 
               
               
                   
               
               
                   
                 AATTTCGGATGCTATCTTGGAAGATTATGCTTCCA 
               
               
                   
               
               
                   
                 TGCAGTGAGAGGAAGA 
               
               
                   
               
               
                   
                 GOD-E 
               
               
                   
                 SEQ ID NO: 7 
               
               
                   
                 GAATTCAGCAATGGCATTGAAGCCAGCCTCCTGAC 
               
               
                   
               
               
                   
                 TGATCCCAAGGATGTCTCCGGCCGCACGGTCGACT 
               
               
                   
               
               
                   
                 ACATCATCGCTGGTGGAGGTCTGACTGGACTCACC 
               
               
                   
               
               
                   
                 ACCGCTGCTCGTCTGACGGAGAACCCCAACATCAG 
               
               
                   
               
               
                   
                 TGTGCTCGTCATCGAAAGTGGCTCCTACGAGTCGG 
               
               
                   
               
               
                   
                 ACAGAGGTCCTATCATTGAGGACCTGAACGCCTAC 
               
               
                   
               
               
                   
                 GGCGACATCTTTGGCAGCAGTGTAGACCACGCCTA 
               
               
                   
               
               
                   
                 CGAGACCGTGGAGCTCGCTTGCAACAATCAAACCG 
               
               
                   
               
               
                   
                 CGCTGATCCGCTCCGGAAATGGTCTCGGTGGCTCT 
               
               
                   
               
               
                   
                 ACTCTAGTGAATGGTGGCACGGGACTCGCCCCCAC 
               
               
                   
               
               
                   
                 AAGGCACAGGTTGACTCTTGGGAGACTGTCTTTGG 
               
               
                   
               
               
                   
                 AAATGAGGGCTGGAACTGGGACAATGTGGCCGCCT 
               
               
                   
               
               
                   
                 ACTCCCTCCAGGCTGAGCGTGCTCGCGCACCAAAT 
               
               
                   
               
               
                   
                 GCCAAACAGATCGCTGCTGGCCACTACTTCAACGC 
               
               
                   
               
               
                   
                 ATCCTGCCATGGTGTTAATGGTACTGTCCATGCCG 
               
               
                   
               
               
                   
                 GACCCCGCGACACCGGCGATGACTATTCTCCCATC 
               
               
                   
               
               
                   
                 GTCAAGGCTCTCATGAGCGCTGTCGAAGACCGGGG 
               
               
                   
               
               
                   
                 CGTTCCCACCAAGAAAGACTTCGGATGCGGTGACC 
               
               
                   
               
               
                   
                 CCCATGGTGTGTCCATGTTCCCCAACACCTTGCAC 
               
               
                   
               
               
                   
                 GAAGACCAAGTGCGCTCCGATGCCGCTCGCGAATG 
               
               
                   
               
               
                   
                 GCTACTTCCCAACTACCAACGTCCCAACCTGCAAG 
               
               
                   
               
               
                   
                 TCCTGACCGGACAGTATGTTGGTAAGGTGCTCCTT 
               
               
                   
               
               
                   
                 AGCCAGAACGGCACCACCCCTCGTGCCGTTGGCGT 
               
               
                   
               
               
                   
                 GGAATTCGGCACCCACAAGGGCAACACCCACAACG 
               
               
                   
               
               
                   
                 TTTACGCTAAGCACGAGGTCCTCCTGGCCGCGGGC 
               
               
                   
               
               
                   
                 TCCGCTGTCTCTCCCACAATCCTCGAATATTCCGG 
               
               
                   
               
               
                   
                 TATCGGAATGAAGTCCATCCTGGAGCCCCTTGGTA 
               
               
                   
               
               
                   
                 TCGACACCGTCGTTGACCTGCCCGTCGGCTTGAAC 
               
               
                   
               
               
                   
                 CTGCAGGACCAGACCACCGCTACCGTCCGCTCCCG 
               
               
                   
               
               
                   
                 CATCACCTCTGCTGGTGCAGGACAGGGACAGGCCG 
               
               
                   
               
               
                   
                 CTTGGTTCGCCACCTTCAACGAGACCTTTGGTGAC 
               
               
                   
               
               
                   
                 TATTCCGAAAAGGCACACGAGCTGCTCAACACCAA 
               
               
                   
               
               
                   
                 GCTGGAGCAGTGGGCCGAAGAGGCCGTCGCCCGTG 
               
               
                   
               
               
                   
                 GCGGATTCCACAACACCACCGCCTTGCTCATCCAG 
               
               
                   
               
               
                   
                 TACGAGAACTACCGCGACTGGATTGTCAACCACAA 
               
               
                   
               
               
                   
                 CGTCGCGTACTCGGAACTCTTCCTCGACACTGCCG 
               
               
                   
               
               
                   
                 GAGTAGCCAGCTTCGATGTGTGGGACCTTCTGCCC 
               
               
                   
               
               
                   
                 TTCACCCGAGGATACGTTCACATCCTCGACAAGGA 
               
               
                   
               
               
                   
                 CCCCTACCTTCACCACTTCGCCTACGACCCTCAGT 
               
               
                   
               
               
                   
                 ACTTCCTCAACGAGCTGGACCTGCTCGGTCAGGCT 
               
               
                   
               
               
                   
                 GCCGCTACTCAACTGGCCCGCAACATCTCCAACTC 
               
               
                   
               
               
                   
                 CGGTGCCATGCAGACCTACTTCGCTGGGGAGACTA 
               
               
                   
               
               
                   
                 TCCCCGGTGATAACCTCGCGTATGATGCCGATTTG 
               
               
                   
               
               
                   
                 AGCGCCTGGACTGAGTACATCTGCTACCACTTCCG 
               
               
                   
               
               
                   
                 TCCTAACTACCATGGCGTGGGTACTTGCTCCATGA 
               
               
                   
               
               
                   
                 TGCCGAAGGAGATGGGCGGTGTTGTTGATAATGCT 
               
               
                   
               
               
                   
                 GCCCGTGTGTATGGTGTGCAGGGACTGCGTGTCAT 
               
               
                   
               
               
                   
                 TGATGGTTCTATTCCTCCTACGCAAATGTCGTCCC 
               
               
                   
               
               
                   
                 ATGTCATGACGGTGTTCTATGCCATGGCGCTAAAA 
               
               
                   
               
               
                   
                 ATTTCGGATGCTATCTTGGAAGATTATGCTTCCAT 
               
               
                   
               
               
                   
                 GCAGTGAGAGGAAGA 
               
               
                   
               
               
                   
                 F19 
               
               
                   
                 SEQ ID NO: 8 
               
               
                   
                 SNGIEASLLTDPKDVSGRTVDYIIAGGGLVGLTTA 
               
               
                   
               
               
                   
                 AKLTENPNISVLVIESGSYESDRGPIIEDLNAYGD 
               
               
                   
               
               
                   
                 IFGSSVDHAYETVELATNNQTALVRSGNGLGGSTI 
               
               
                   
               
               
                   
                 INGGTWTRPHKAQVDSWETVFGNEGWNWDNVAAYS 
               
               
                   
               
               
                   
                 LQAERARAPNAKQIAAGHYFNTSCHGVNGTVHAGP 
               
               
                   
               
               
                   
                 RDTGDDYSPIVKALMSAVEDRGVPIKKDFGCGDPH 
               
               
                   
               
               
                   
                 GVSMFPNTLHEDQVRSDAAREWLLPNYQRPNLQVL 
               
               
                   
               
               
                   
                 TGQYVGKVLLSQNGTTPRAVGVEFGTHKGNTHNVY 
               
               
                   
               
               
                   
                 AKHEVLLAAGSAVSPTILEYSGIGMKSILEPLGID 
               
               
                   
               
               
                   
                 TVVDLPVGLNLQDQTTATVRSRITSAGAGQGQAAW 
               
               
                   
               
               
                   
                 FATFNETFGDYSEKAHELLNTKLEQWAEEAVARGG 
               
               
                   
               
               
                   
                 FHNTTALLIQYENYRDWIVNHNVAYSELFLDTAGV 
               
               
                   
               
               
                   
                 ASFDVWDLLPFTRGYVHILDKDPYLEHFAYDPQYF 
               
               
                   
               
               
                   
                 LNELDLLGQAAATQLARNISNSGAMQTYFAGETIP 
               
               
                   
               
               
                   
                 GDNLAYDADLSAWTEYIPYHFRPNYHGVGTCSMMP 
               
               
                   
               
               
                   
                 KEIVIGGVVDNAARVYGVQGLRVIDGSIPPTQMSS 
               
               
                   
               
               
                   
                 HVMTVFYAMALKISDAILEDYASMQ 
               
               
                   
               
               
                   
                 SEQ ID NO: 9 
               
               
                   
                 SNGIEASLLTDPKEVAGRTVDYIIAGGGLIGLITA 
               
               
                   
               
               
                   
                 ARLTENPDITVLVIESGSYESDRGPIIEDLNAYGD 
               
               
                   
               
               
                   
                 IFGSSVDHAYETVELATNNQTALIRSGNGLGGSTL 
               
               
                   
               
               
                   
                 VNGGTWTRPHKAQVDSWETVFGNEGWNWDSVAAYS 
               
               
                   
               
               
                   
                 LQAERARAPNAKQIAAGHYFNASCHGINGTVHAGP 
               
               
                   
               
               
                   
                 RDTGDDYSPIVKALMSAVEDRGVPIKKDLGCGDPH 
               
               
                   
               
               
                   
                 GVSMFPNTLEIEDQVRSDAAREWLLPNYQRPNLQV 
               
               
                   
               
               
                   
                 LTGQYVGKVLLSQNATTPRAVGVEFGTHKGNTHNV 
               
               
                   
               
               
                   
                 YAKHEVLLAAGSAVSPTILEYSGIGMKSILEPLGI 
               
               
                   
               
               
                   
                 DTVVDLPVGLNLQDQTTSTVRSRITSAGAGQGQAA 
               
               
                   
               
               
                   
                 WFATFNETFGDYTEKAHELLNTKLEQWAEEAVARG 
               
               
                   
               
               
                   
                 GFHNTTALLIQYENYRDWIVKDNVAYSELFLDTAG 
               
               
                   
               
               
                   
                 VASFDVWDLLPFTRGYVHILDKDPYLRHFAYDPQY 
               
               
                   
               
               
                   
                 FLNELDLLGQAAATQLARNISNSGAMQTYFAGETI 
               
               
                   
               
               
                   
                 PGDNLAYDADLRAWVEYIPYNFRPNYHGVGTCSMI 
               
               
                   
               
               
                   
                 MPKEMGGVVDNAARVYGVQGLRVIDGSIPPTQMSS 
               
               
                   
               
               
                   
                 HVMTVFYAMALKIADAVLADYASMQ 
               
               
                   
               
               
                   
                 GOD-M5 
               
               
                   
                 SEQ ID NO: 10 
               
               
                   
                 SNGIEASLLTDPKEVAGRTVDYIIAGGGLTGLTVA 
               
               
                   
               
               
                   
                 ARLTENPDITVLVIESGSYESDRGPIIEDLNAYGD 
               
               
                   
               
               
                   
                 WGSSVDHAYETVCLATNNQTALIRSGNGLGGSTLV 
               
               
                   
               
               
                   
                 NGGTWTRPHKAQVDSWETVFGNEGWNWDSVAAYSL 
               
               
                   
               
               
                   
                 QAERARAPNAKQIAAGHYFNASCHGINGTVHAGPR 
               
               
                   
               
               
                   
                 DTGDDYSPIVKALMSAVEDRGVPIKKDLGCGDPHG 
               
               
                   
               
               
                   
                 VSMFPNTLHEDQVRSDAAREWLLPNYQRPNLQVLT 
               
               
                   
               
               
                   
                 GQYVGKVLLSQNATTPRAVGVEFGTHKGNTHNVYA 
               
               
                   
               
               
                   
                 KHEVLLAAGSAVSPTILEYSGIGMKSTLEPLGIKT 
               
               
                   
               
               
                   
                 VVDLPVGLNLQDQTTSTVRSRITSAGAGQGQAAWF 
               
               
                   
               
               
                   
                 ATFNETFGDYTEKAHELLNTKLEQWAEEAVARGGF 
               
               
                   
               
               
                   
                 HNTTALLIQYENYRDWIVKDNVAYSELFLDTAGEA 
               
               
                   
               
               
                   
                 SFDVWDLLPFTRGYVHILDKDPYLRHFAYDPQYFL 
               
               
                   
               
               
                   
                 NELDLLGQAAATQLARNISNSGAMQTYFAGETIPG 
               
               
                   
               
               
                   
                 DNLAYDADLRAWVEYIPYHFRPNYHGVGTCSMMPK 
               
               
                   
               
               
                   
                 EMGGVVDNAARVYGVQGLRVIDGSIPPTQMSSHVM 
               
               
                   
               
               
                   
                 TVFYAMALKIADAVLADYASMQ 
               
               
                   
               
               
                   
                 GOD-A 
               
               
                   
                 SEQ ID NO: 11 
               
               
                   
                 SNGIEASLLTDPKDVSGRTVDYIIAGGGLTGLTTA 
               
               
                   
               
               
                   
                 ARLTENPNISVLVIESGCYESDRGPIIEDLNAYGD 
               
               
                   
               
               
                   
                 IFGSSVDHAYETVELATNNQTALIRSGNGLGGSTL 
               
               
                   
               
               
                   
                 VNGGTWTRPHKAQVDSWETVFGNEGWNWDNVAAYS 
               
               
                   
               
               
                   
                 LQAERARAPNAKQIAAGHYFNASCHGVNGTVHAGP 
               
               
                   
               
               
                   
                 RDTGDDYSPIVKALMSAVEDRGVPTKKDFGCGDPH 
               
               
                   
               
               
                   
                 GVSMFPNTLHEDQVRSDAAREWLLPNYQRPNLQVL 
               
               
                   
               
               
                   
                 CGQYVGKVLLSQNGTTPRAVGVEFGTHKGNTHNVY 
               
               
                   
               
               
                   
                 AKHEVLLAAGSAVSPTILEYSGIGMKSILEPLGID 
               
               
                   
               
               
                   
                 TVVDLPVGLNLQDQTTATVRSRITSAGAGQGQAAW 
               
               
                   
               
               
                   
                 FATFNETFGDYSEKAHELLNTKLEQWAEEAVARGG 
               
               
                   
               
               
                   
                 FHNTTALLIQYENYRDWIVNHNVAYSELFLDTAGV 
               
               
                   
               
               
                   
                 ASFDVWDLLPFTRGYVHILDKDPYLHHFAYDPQYF 
               
               
                   
               
               
                   
                 LNELDLLGQAAATQLARNISNSGAMQTYFAGETIP 
               
               
                   
               
               
                   
                 GDNLAYDADLSAWTEYIPYHFRPNYHGVGICSMIM 
               
               
                   
               
               
                   
                 PKEMGGVVDNAARVYGVQGLRVIDGSIPPTQMSSH 
               
               
                   
               
               
                   
                 VMTVFYAMALKISDAILEDYASMQ 
               
               
                   
               
               
                   
                 GOD-B 
               
               
                   
                 SEQ ID NO: 12 
               
               
                   
                 SNGILASLLTDPKDVSGRTVDYIICGGGLTGLTTA 
               
               
                   
               
               
                   
                 ARLTENPNISVLVIESGSYESDRGPIIEDLNAYGD 
               
               
                   
               
               
                   
                 WGSSVDHAYETVELATNNQTALIRSGNGLGGSTLV 
               
               
                   
               
               
                   
                 NGGTWTRPHKAQVDSWETVFGNEGWNWDNVAAYSL 
               
               
                   
               
               
                   
                 QAERARAPNAKQIAAGHYFNASCHGVNGTVHAGPR 
               
               
                   
               
               
                   
                 DTGDDYSPIVKALMSAVEDRGVPTKKDFGCGDPHG 
               
               
                   
               
               
                   
                 VSNIFPNTLHEDQVRSDAAREWLLPNYQRPNLQVL 
               
               
                   
               
               
                   
                 TGQYCGKVLLSQNGTTPRAVGVEFGTHKGNTHNVY 
               
               
                   
               
               
                   
                 AKHEVLLAAGSAVSPTILEYSGIGMKSILEPLGID 
               
               
                   
               
               
                   
                 TVVDLPVGLNLQDQTTATVRSRITSAGAGQGQAAW 
               
               
                   
               
               
                   
                 FATFNETFGDYSEKAHELLNTKLEQWAEEAVARGG 
               
               
                   
               
               
                   
                 FHNTTALLIQYENYRDWIVNHNVAYSFLFLDTAGV 
               
               
                   
               
               
                   
                 ASFDVWDLLPFTRGYVHILDKDPYLHHFAYDPQYF 
               
               
                   
               
               
                   
                 LNELDLLGQAAATQLARNISNSGAMQTYFAG 
               
               
                   
               
               
                   
                 ETIPGDNLAYDADLSAWTEYIPYHFRPNYHGVGTC 
               
               
                   
               
               
                   
                 SMMPKEMGGVVDNAARVYGVQGLRVIDGSIPPTQM 
               
               
                   
               
               
                   
                 SSHVMTVFYAMALKISDAILEDYASMQ 
               
               
                   
               
               
                   
                 GOD-C 
               
               
                   
                 SEQ ID NO: 13 
               
               
                   
                 SNGIEASLLTDPKDVSGRTCDYIIAGGGLTGLTTA 
               
               
                   
               
               
                   
                 ARLIENPNICVLVIESGSYESDRGPIIEDLNAYGD 
               
               
                   
               
               
                   
                 WGSSVDHAYETVELATNNQTALIRSGNGLGGSTLV 
               
               
                   
               
               
                   
                 NGGTWTRPHKAQVDSWETVFGNEGWNWDNVAAYSL 
               
               
                   
               
               
                   
                 QAERARAPNAKQIAAGHYFNASCHGVNGTVHAGPR 
               
               
                   
               
               
                   
                 DTGDDYSPIVKALMSAVEDRGVPTKKDFGCGDPHG 
               
               
                   
               
               
                   
                 VSNIFPNTLHEDQVRSDAAREWLLPNYQRPNLQVL 
               
               
                   
               
               
                   
                 TGQYVGKVLLSQNGTTPRAVGVEFGTHKGNTHNVY 
               
               
                   
               
               
                   
                 AKHEVLLAAGSAVSPTILEYSGIGMKSILEPLGID 
               
               
                   
               
               
                   
                 TVVDLPVGLNLQDQTTATVRSRITSAGAGQGQAAW 
               
               
                   
               
               
                   
                 FATFNETFGDYSEKAHELLNTKLEQWAEEAVARGG 
               
               
                   
               
               
                   
                 FHNTTALLIQYENYRDWIVNHNVAYSELFLDTAGV 
               
               
                   
               
               
                   
                 ASFDVWDLLPFTRGYVHILDKDPYLHIWAYDPQYF 
               
               
                   
               
               
                   
                 LNELDLLGQAAATQLARNISNSGAMQTYFAGETIP 
               
               
                   
               
               
                   
                 GDNLAYDADLSAWTEYIPYHFRPNYHGVGTCSMIM 
               
               
                   
               
               
                   
                 PKEMGGVVDNAARVYGVQGLRVIDGSIPPTQMSSH 
               
               
                   
               
               
                   
                 VMTVFYAMALKISDAILEDYASMQ 
               
               
                   
               
               
                   
                 GOD-D 
               
               
                   
                 SEQ ID NO: 14 
               
               
                   
                 SNGIEASLLTDPKDVSGRTVDYIIAGGGLTGLTTA 
               
               
                   
               
               
                   
                 ARLCENPNISVLVIESGSYESDRGPIIEDLNAYGD 
               
               
                   
               
               
                   
                 IFGSSVDHAYETVELATNNQTALIRSGNGLGGSTL 
               
               
                   
               
               
                   
                 VNGGTWTRPHKAQVDSWETVFGNEGWNWDNVAAYS 
               
               
                   
               
               
                   
                 LQAERARAPNAKQIAAGHYFNASCHGVNGTVHAGP 
               
               
                   
               
               
                   
                 RDTGDDYSPIVKALMSAVEDRGVPTKKDFGCGDPH 
               
               
                   
               
               
                   
                 GVSMFPNTLHEDQVRSDAAREWLLPNYQRPNCQVL 
               
               
                   
               
               
                   
                 TGQYVGKVLLSQNGTTPRAVGVEFGTHKGNTHNVY 
               
               
                   
               
               
                   
                 AKHEVLLAAGSAVSPTILEYSGIGMKSILEPLGID 
               
               
                   
               
               
                   
                 TVVDLPVGLNLQDQTTATVRSRITSAGAGQGQAAW 
               
               
                   
               
               
                   
                 FATFNETFGDYSEKAHELLNTKLEQWAEEAVARGG 
               
               
                   
               
               
                   
                 FHNTTALLIQYENYRDWIVNHNVAYSELFLDTAGV 
               
               
                   
               
               
                   
                 ASFDVWDLLPFTRGYVHILDKDPYLITHFAYDPQY 
               
               
                   
               
               
                   
                 FLNELDLLGQAAATQLARNISNSGAMQTYFAGETI 
               
               
                   
               
               
                   
                 PGDNLAYDADLSAWTEYIPYHFRPNYHGVGTCSMM 
               
               
                   
               
               
                   
                 PKEMGGVVDNAARVYGVQGLRVIDGSIPPTQMSSH 
               
               
                   
               
               
                   
                 VMTVFYAMALKISDAILEDYASMQ 
               
               
                   
               
               
                   
                 GOD-E 
               
               
                   
                 SEQ ID NO: 15 
               
               
                   
                 SNGIEASLLTDPKDVSGRTVDYIIAGGGLTGLTTA 
               
               
                   
               
               
                   
                 ARLTENPNISVLVIESGSYESDRGPIIEDLNAYGD 
               
               
                   
               
               
                   
                 IFGSSVDHAYETVELACNNQTALIRSGNGLGGSTL 
               
               
                   
               
               
                   
                 VNGGIWTRPIIKAQVDSWETVFGNEGWNWDNVAAY 
               
               
                   
               
               
                   
                 SLQAERARAPNAKQIAAGHYFNASCHGVNGTVHAG 
               
               
                   
               
               
                   
                 PRDTGDDYSPIVKALMSAVEDRGVPTKKDFGCGDP 
               
               
                   
               
               
                   
                 HGVSMFPNTLHEDQVRSDAAREWLLPNYQRPNLQV 
               
               
                   
               
               
                   
                 LTGQYVGKVLLSQNGTTPRAVGVEFGTHKGNTHNV 
               
               
                   
               
               
                   
                 YAKHEVLLAAGSAVSPTILEYSGIGMKSILEPLGI 
               
               
                   
               
               
                   
                 DTVVDLPVGLNLQDQTTATVRSRITSAGAGQGQAA 
               
               
                   
               
               
                   
                 WFATFNETFGDYSEKAHELLNTKLEQWAEEAVARG 
               
               
                   
               
               
                   
                 GFHNTTALLIQYENYRDWIVNHNVAYSELFLDTAG 
               
               
                   
               
               
                   
                 VASFDVWDLLPFTRGYVHILDKOPYLFITIFAYDP 
               
               
                   
               
               
                   
                 QYFLNELDLLGQAAATQLARNISNSGAMQTYFAGE 
               
               
                   
               
               
                   
                 TIPGDNLAYDADLSAWTEYICYHFRPNYHGVGTCS 
               
               
                   
               
               
                   
                 MMPKEMGGVVDNAARVYGVQGLRVIDGSIPPTQMS 
               
               
                   
               
               
                   
                 SHVMTVFYAMALKISDAILEDYASMQ 
               
               
                   
               
               
                   
                 F19-A 
               
               
                   
                 SEQ ID NO: 16 
               
               
                   
                 GAATTCAGCAATGGCATTGAAGCCAGCCTCCTGAC 
               
               
                   
               
               
                   
                 TGATCCCAAGGATGMTCCGGCCGCACGGTCGACTA 
               
               
                   
               
               
                   
                 CATCATCGCTGGTGGAGGTCTGGTGGGACTCACCA 
               
               
                   
               
               
                   
                 CCGCTGCTAAGCTGACGGAGAACCCCAACATCAGT 
               
               
                   
               
               
                   
                 GTGCTCGTCATCGAAAGTGGCTGCTACGAGTCGGA 
               
               
                   
               
               
                   
                 CAGAGGTCGATCATTGAGGACCTGAACGCCTACGG 
               
               
                   
               
               
                   
                 CGACATCTTTGGCAGCAGTGTAGACCACGCCTACG 
               
               
                   
               
               
                   
                 AGACCGTGGAGCTCGCTACCAACAATCAAACCGCG 
               
               
                   
               
               
                   
                 CTGGTGCGCTCCGGAAATGGTCTCGGTGGCTCTAC 
               
               
                   
               
               
                   
                 TCTAATCAATGGTGGCACCTGGACTCGCCCCCACA 
               
               
                   
               
               
                   
                 AGGCACAGGTTGACTCTTGGGAGACTGTCTTTGGA 
               
               
                   
               
               
                   
                 AATGAGGGCTGGAACTGGGACAATGTGGCCGCCTA 
               
               
                   
               
               
                   
                 CTCCCTCCAGGCTGAGCGTGCTCGCGCACCAAATG 
               
               
                   
               
               
                   
                 CCAAACAGATCGCTGCTGGCCACTACTTCAACACC 
               
               
                   
               
               
                   
                 TCCTGCCATGGTGTTAATGGTACTGTCCATGCCGG 
               
               
                   
               
               
                   
                 ACCCCGCGACACCGGCGATGACTATTCTCCCATCG 
               
               
                   
               
               
                   
                 TCAAGGCTCTCATGAGCGCTGTCGAAGACCGGGGC 
               
               
                   
               
               
                   
                 GTTCCCACCAAGAAAGACTTCGGATGCGGTGACCC 
               
               
                   
               
               
                   
                 CCATGGTGTGTCCATGTTCCCCAACACCTTGCACG 
               
               
                   
               
               
                   
                 AAGACCAAGTGCGCTCCGATGCCGCTCGCGAATGG 
               
               
                   
               
               
                   
                 CTACTTCCCAACTACCAACGTCCCAACCTGCAAGT 
               
               
                   
               
               
                   
                 CCTGTGCGGACAGTATGTTGGTAAGGTGCTCCTTA 
               
               
                   
               
               
                   
                 GCCAGAACGGCACCACCCCTCGTGCCGTTGGCGTG 
               
               
                   
               
               
                   
                 GAATTCGGCACCCACAAGGGCAACACCCACAACGT 
               
               
                   
               
               
                   
                 TTACGCTAAGCACGAGGTCCTCCTGGCCGCGGGCT 
               
               
                   
               
               
                   
                 CCGCTGTCTCTCCCACAATCCTCGAATATTCCGGT 
               
               
                   
               
               
                   
                 ATCGGAATGAAGTCCATCCTGGAGCCCCTTGGTAT 
               
               
                   
               
               
                   
                 CGACACCGTCGTTGACCTGCCCGTCGGCTTGAACC 
               
               
                   
               
               
                   
                 TGCAGGACCAGACCACCGCTACCGTCCGCTCCCGC 
               
               
                   
               
               
                   
                 ATCACCTCTGCTGGTGCAGGACAGGGACAGGCCGC 
               
               
                   
               
               
                   
                 TTGGTTCGCCACCTTCAACGAGACCTTTGGTGACT 
               
               
                   
               
               
                   
                 ATTCCGAAAAGGCACACGAGCTGCTCAACACCAAG 
               
               
                   
               
               
                   
                 CTGGAGCAGTGGGCCGAAGAGGCCGTCGCCCGTGG 
               
               
                   
               
               
                   
                 CGGATTCCACAACACCACCGCCTTGCTCATCCAGT 
               
               
                   
               
               
                   
                 ACGAGAACTACCGCGACTGGATTGTCAACCACAAC 
               
               
                   
               
               
                   
                 GTCGCGTACTCGGAACTCTTCCTCGACACTGCCGG 
               
               
                   
               
               
                   
                 AGTAGCCAGCTTCGATGTGTGGGACCTTCTGCCCT 
               
               
                   
               
               
                   
                 TCACCCGAGGATACGTTCACATCCTCGACAAGGAC 
               
               
                   
               
               
                   
                 CCCTACCTTCACCACTTCGCCTACGACCCTCAGTA 
               
               
                   
               
               
                   
                 CTTCCTCAACGAGCTGGACCTGCTCGGTCAGGCTG 
               
               
                   
               
               
                   
                 CCGCTACTCAACTGGCCCGCAACATCTCCAACTCC 
               
               
                   
               
               
                   
                 GGTGCCATGCAGACCTACTTCGCTGGGGAGACTAT 
               
               
                   
               
               
                   
                 CCCCGGTGATAACCTCGCGTATGATGCCGATTTGA 
               
               
                   
               
               
                   
                 GCGCCTGGACTGAGTACATCCCGTACCACTTCCGT 
               
               
                   
               
               
                   
                 CCTAACTACCATGGCGTGGGTACTTGCTCCATGAT 
               
               
                   
               
               
                   
                 GCCGAAGGAGATGGGCGGTGTTGTTGATAATGCTG 
               
               
                   
               
               
                   
                 CCCGTGTGTATGGTGTGCAGGGACTGCGTGTCATT 
               
               
                   
               
               
                   
                 GATGGTTCTATTCCTCCTACGCAAATGTCGTCCCA 
               
               
                   
               
               
                   
                 TGTCATGACGGTGTTCTATGCCATGGCGCTAAAAA 
               
               
                   
               
               
                   
                 TTTCGGATGCTATCTTGGAAGATTATGCTTCCATG 
               
               
                   
               
               
                   
                 CAGTGAGAGGAAGA 
               
               
                   
               
               
                   
                 F19-A 
               
               
                   
                 SEQ ID NO: 17 
               
               
                   
                 SNGIEASLLTDPKDVSGRTVDYIIAGGGLVGLTTA 
               
               
                   
               
               
                   
                 AKLTENPNISVLVIESGCYESDRGPIIEDLNAYGD 
               
               
                   
               
               
                   
                 IFGSSVDHAYETVELATNNQTALVRSGNGLGGSTL 
               
               
                   
               
               
                   
                 INGGTWTRPHKAQVDSWETVFGNEGWNWDNVAAYS 
               
               
                   
               
               
                   
                 LQAERARAPNAKQIAAGHYFNTSCHGVNGTVHAGP 
               
               
                   
               
               
                   
                 RDTGDDYSPIVKALMSAVEDRGVPTKKDFCCGDPH 
               
               
                   
               
               
                   
                 GVSMFPNTLHEDQVRSDAAREWLLPNYQRPNLQVL 
               
               
                   
               
               
                   
                 CGQYVGKVLLSQNGTTPRAVGVEFGTHKGNTHNVY 
               
               
                   
               
               
                   
                 AKHEVLLAAGSAVSPTILEYSGIGMKSILEPLGID 
               
               
                   
               
               
                   
                 TVVDLPVGLNLQDQTTATVRSRITSAGAGQGQAAW 
               
               
                   
               
               
                   
                 FATFNETFGDYSEKAHELLNTKLEQWAEEAVARGG 
               
               
                   
               
               
                   
                 FHNTTALLIQYENYRDWIVNHNVAYSELFLDTAGV 
               
               
                   
               
               
                   
                 ASFDVWDLLPFTRGYVHILDKDPYLEHFAYDPQYF 
               
               
                   
               
               
                   
                 LNELDLLGQAAATQLARNISNSGAMQTYFAGETIP 
               
               
                   
               
               
                   
                 GDNLAYDADLSAWTEYWYHFRPNYHGVGTCSMMPK 
               
               
                   
               
               
                   
                 EMGGVVDNAARVYGVQGLRVIDGSIPPTQMSSHVM 
               
               
                   
               
               
                   
                 TVFYAMALKISDAILEDYASMQ 
               
               
                   
               
               
                   
                 F19-B 
               
               
                   
                 SEQ ID NO: 18 
               
               
                   
                 GAATTCAGCAATGGCATTGAAGCCAGCCTCCTGAC 
               
               
                   
               
               
                   
                 TGATCCCAAGGATGICTCCGGCCGCACGGTCGACT 
               
               
                   
               
               
                   
                 ACATCATCTGCGGTGGAGGTCTGGTGGGACTCACC 
               
               
                   
               
               
                   
                 ACCGCTGCTAAGCTGACGGAGAACCCCAACATCAG 
               
               
                   
               
               
                   
                 TGTGCTCGTCATCGAAAGTGGCTCCTACGAGTCGG 
               
               
                   
               
               
                   
                 ACAGAGGTCCTATCATTGAGGACCTGAACGCCTAC 
               
               
                   
               
               
                   
                 GGCGACATCTTTGGCAGCAGTGTAGACCACGCCTA 
               
               
                   
               
               
                   
                 CGAGACCGTGGAGCTCGCTACCAACAATCAAACCG 
               
               
                   
               
               
                   
                 CGCTGGTGCGCTCCGGAAATGGTCTCGGTGGCTCT 
               
               
                   
               
               
                   
                 ACTCTAATCAATGGTGGCACCTGGACTCGCCCCCA 
               
               
                   
               
               
                   
                 CAAGGCACAGGTTGACTCTTGGGAGACTGTCTTTG 
               
               
                   
               
               
                   
                 GAAATGAGGGCTGGAACTGGGACAATGTGGCCGCC 
               
               
                   
               
               
                   
                 TACTCCCTCCAGGCTGAGCGTGCTCGCGCACCAAA 
               
               
                   
               
               
                   
                 TGCCAAACAGATCGCTGCTGGCCACTACTTCAACA 
               
               
                   
               
               
                   
                 CCTCCTGCCATGGTGTTAATGGTACTGTCCATGCC 
               
               
                   
               
               
                   
                 GGACCCCGCGACACCGGCGATGACTATTCTCCCAT 
               
               
                   
               
               
                   
                 CGTCAAGGCTCTCATGAGCGCTGTCGAAGACCGGG 
               
               
                   
               
               
                   
                 GCGTTCCCACCAAGAAAGACTTCGGATGCGGTGAC 
               
               
                   
               
               
                   
                 CCCCATGGTGTGTCCATGTTCCCCAACACCTTGCA 
               
               
                   
               
               
                   
                 CGAAGACCAAGTGCGCTCCGATGCCGCTCGCGAAT 
               
               
                   
               
               
                   
                 GGCTACTTCCCAACTACCAACGTCCCAACCTGCAA 
               
               
                   
               
               
                   
                 GTCCTGACCGGACAGTATTGCGGTAAGGTGCTCCT 
               
               
                   
               
               
                   
                 TAGCCAGAACGGCACCACCCCTCGTGCCGTTGGCG 
               
               
                   
               
               
                   
                 TGGAATTCGGCACCCACAAGGGCAACACCCACAAC 
               
               
                   
               
               
                   
                 GTTTACGCTAAGCACGAGGICCTCCTGGCCGCGGG 
               
               
                   
               
               
                   
                 CTCCGCTGTCTCTCCCACAATCCTCGAATATTCCG 
               
               
                   
               
               
                   
                 GTATCGGAATGAAGTCCATCCTGGAGCCCCTTGGT 
               
               
                   
               
               
                   
                 ATCGACACCGTCGTTGACCTGCCCGTCGGCTTGAA 
               
               
                   
               
               
                   
                 CCTGCAGGACCAGACCACCGCTACCGTCCGCTCCC 
               
               
                   
               
               
                   
                 GCATCACCTCTGCTGGTGCAGGACAGGGACAGGCC 
               
               
                   
               
               
                   
                 GCTTGGTTCGCCACCTTCAACGAGACCTTTGGTGA 
               
               
                   
               
               
                   
                 CTATTCCGAAAAGGCACACGAGCTGCTCAACACCA 
               
               
                   
               
               
                   
                 AGCTGGAGCAGTGGGCCGAAGAGGCCGTCGCCCGT 
               
               
                   
               
               
                   
                 GGCGGATTCCACAACACCACCGCCTTGCTCATCCA 
               
               
                   
               
               
                   
                 GTACGAGAACTACCGCGACTGGATTGTCAACCACA 
               
               
                   
               
               
                   
                 ACGTCGCGTACTCGGAACTCTTCCTCGACACTGCC 
               
               
                   
               
               
                   
                 GGAGTAGCCAGCTTCGATGTGTGGGACCTTCTGCC 
               
               
                   
               
               
                   
                 CTTCACCCGAGGATACGTTCACATCCTCGACAAGG 
               
               
                   
               
               
                   
                 ACCCCTACCTTCACCACTTCGCCTACGACCCTCAG 
               
               
                   
               
               
                   
                 TACTTCCTCAACGAGCTGGACCTGCTCGGTCAGGC 
               
               
                   
               
               
                   
                 TGCCGCTACTCAACTGGCCCGCAACATCTCCAACT 
               
               
                   
               
               
                   
                 CCGGTGCCATGCAGACCTACTTCGCTGGGGAGACT 
               
               
                   
               
               
                   
                 ATCCCCGGTGATAACCTCGCGTATGATGCCGATTT 
               
               
                   
               
               
                   
                 GAGCGCCTGGACTGAGTACATCCCGTACCACTTCC 
               
               
                   
               
               
                   
                 GTCCTAACTACCATGGCGTGGGTACTTGCTCCATG 
               
               
                   
               
               
                   
                 ATGCCGAAGGAGATGGGCGGTGTTGTTGATAATGC 
               
               
                   
               
               
                   
                 TGCCCGTGTGTATGGTGTGCAGGGACTGCGTGTCA 
               
               
                   
               
               
                   
                 TTGATGGTTCTATTCCTCCTACGCAAATGTCGTCC 
               
               
                   
               
               
                   
                 CATGTCATGACGGTGTTCTATGCCATGGCGCTAAA 
               
               
                   
               
               
                   
                 AATTTCGGATGCTATCTTGGAAGATTATGCTTCCA 
               
               
                   
               
               
                   
                 TGCAGTGAGAGGAAGA 
               
               
                   
               
               
                   
                 F19-B 
               
               
                   
                 SEQ ID NO: 19 
               
               
                   
                 SNGIEASLLTDPKDVSGRTVDYIICGGGLVGLTTA 
               
               
                   
               
               
                   
                 AKLTENPNISVLVIESGSYESDRGPIIEDLNAYGD 
               
               
                   
               
               
                   
                 IFGSSVDHAYETVELATNNQTALVRSGNGLGGSTL 
               
               
                   
               
               
                   
                 INGGTWTRPHKAQVDSWETVFGNEGWNWDNVAAYS 
               
               
                   
               
               
                   
                 LQAERARAPNAKQIAAGHYFNTSCHGVNGTVHAGP 
               
               
                   
               
               
                   
                 RDTGDDYSPIVKALMSAVEDRGVPTKKDFGCGDPH 
               
               
                   
               
               
                   
                 GVSMFPNTLHEDQVRSDAAREWLLPNYQRPNLQVL 
               
               
                   
               
               
                   
                 TGQYCGKVLLSQNGTTPRAVGVEFGTHKGNTHNVY 
               
               
                   
               
               
                   
                 AKHEVLLAAGSAVSPTILEYSGIGMKSILEPLGID 
               
               
                   
               
               
                   
                 TVVDLPVGLNLQDQTTATVRSRITSAGAGQGQAAW 
               
               
                   
               
               
                   
                 FATFNETFGDYSEKAIIELLNTKLEQWAEEAVARG 
               
               
                   
               
               
                   
                 GFHNTTALLIQYENYRDWIVNHNVAYSELFLDTAG 
               
               
                   
               
               
                   
                 VASFDVWDLLPFTRGYVHILDKDPYLHHFAYDPQY 
               
               
                   
               
               
                   
                 FLNELDLLGQAAATQLARNISNSGAMQTYFAGETI 
               
               
                   
               
               
                   
                 PGDNLAYDADLSAWIEYWYHFRPNYHGVGTCSMMP 
               
               
                   
               
               
                   
                 KEMGGVVDNAARVYGVQGLRVIDGSIPPTQMSSHV 
               
               
                   
               
               
                   
                 MTVFYAMALKISDAILEDYASMQ 
               
               
                   
               
               
                   
                 GOD-M5-A 
               
               
                   
                 SEQ ID NO: 20 
               
               
                   
                 GAATTCAGCAATGGAATTGAAGCAAGCCTCCTGAC 
               
               
                   
               
               
                   
                 TGACCCCAAGGAGGTTGCCGGCCGCACTGTCGACT 
               
               
                   
               
               
                   
                 ACATCATCGCTGGTGGAGGTCTGACTGGACTCACC 
               
               
                   
               
               
                   
                 GTCGCTGCCCGTCTGACGGAGAACCCCGATATCAC 
               
               
                   
               
               
                   
                 TGTGCTTGTCATCGAAAGTGGCTGCTACGAGTCTG 
               
               
                   
               
               
                   
                 ACAGAGGTCCTATCATTGAGGACCTGAACGCTTAC 
               
               
                   
               
               
                   
                 GGTGACATTTTTGGCAGCAGTGTGGACCACGCCTA 
               
               
                   
               
               
                   
                 CGAGACTGTCTGCCTCGCCACCAACAATCAGACTG 
               
               
                   
               
               
                   
                 CGCTGATCCGCTCCGGAAATGGTCTCGGTGGCTCT 
               
               
                   
               
               
                   
                 ACCCTCGTCAACGGTGGCACCTGGACTCGCCCCCA 
               
               
                   
               
               
                   
                 CAAGGCACAAGTTGACTCATGGGAGACCGTCTTCG 
               
               
                   
               
               
                   
                 GAAATGAGGGCTGGAACTGGGACAGCGTGGCCGCC 
               
               
                   
               
               
                   
                 TACTCCCTCCAGGCTGAGCGTGCTCGCGCACCAAA 
               
               
                   
               
               
                   
                 TGCCAAACAGATTGCTGCTGGCCACTACTTTAATG 
               
               
                   
               
               
                   
                 CATCCTGCCATGGTATCAATGGTACTGTCCACGCC 
               
               
                   
               
               
                   
                 GGACCCCGCGATACCGGTGATGACTACTCCCCCAT 
               
               
                   
               
               
                   
                 CGTCAAGGCTCTCATGAGCGCTGTCGAAGACAGGG 
               
               
                   
               
               
                   
                 GCGTTCCCACCAAGAAGGACTTGGGATGCGGTGAC 
               
               
                   
               
               
                   
                 CCCCATGGTGTGTCCATGTTCCCCAACACCTTGCA 
               
               
                   
               
               
                   
                 CGAAGACCAAGTGCGCTCTGATGCCGCTCGCGAAT 
               
               
                   
               
               
                   
                 GGCTCCTCCCCAACTACCAGCGTCCCAACCTGCAA 
               
               
                   
               
               
                   
                 GTCCTCTGCGGACAGTATGTTGGAAAGGTCCTGCT 
               
               
                   
               
               
                   
                 CAGCCAGAACGCTACCACACCTCGTGCCGTTGGCG 
               
               
                   
               
               
                   
                 TGGAATTCGGCACCCACAAGGGCAACACCCACAAC 
               
               
                   
               
               
                   
                 GTCTACGCTAAGCACGAGGTCCTCCTGGCCGCTGG 
               
               
                   
               
               
                   
                 ATCCGCTGTCTCTCCCACCATCCTCGAATATTCCG 
               
               
                   
               
               
                   
                 GTATCGGAATGAAGTCCATTCTAGAGCCTCTTGGA 
               
               
                   
               
               
                   
                 ATTAAGACCGTCGTTGACCTGCCCGTTGGTCTCAA 
               
               
                   
               
               
                   
                 CCTTCAGGACCAGACCACCTCTACCGTCCGCTCAC 
               
               
                   
               
               
                   
                 GCATTACCTCCGCCGGTGCCGGACAGGGACAGGCC 
               
               
                   
               
               
                   
                 GCTTGGTTCGCTACCTTCAACGAGACCTTTGGCGA 
               
               
                   
               
               
                   
                 CTACACCGAAAAGGCTCACGAGCTGCTCAACACCA 
               
               
                   
               
               
                   
                 AGCTGGAGCAGTGGGCCGAAGAGGCCGTCGCCCGT 
               
               
                   
               
               
                   
                 GGCGGATTCCACAACACCACCGCTTTGCTCATCCA 
               
               
                   
               
               
                   
                 GTACGAGAACTACCGCGACTGGATCGTCAAGGACA 
               
               
                   
               
               
                   
                 ATGTCGCATACTCGGAACTCTTCCTCGACACGGCC 
               
               
                   
               
               
                   
                 GGAGAAGCCAGTTTCGATGTGTGGGATCTTCTGCC 
               
               
                   
               
               
                   
                 CTTCACTAGAGGATACGTCCACATCCTCGACAAGG 
               
               
                   
               
               
                   
                 ACCCCTACCTCCGCCATTTCGCCTACGACCCTCAG 
               
               
                   
               
               
                   
                 TACTTCCTCAACGAGCTTGACCTGCTCGGCCAGGC 
               
               
                   
               
               
                   
                 TGCCGCCACTCAGCTGGCCCGCAACATCTCTAACT 
               
               
                   
               
               
                   
                 CCGGTGCCATGCAAACTTATTTCGCTGGAGAGACT 
               
               
                   
               
               
                   
                 ATTCCCGGTGACAACCTCGCGTATGATGCCGACTT 
               
               
                   
               
               
                   
                 GAGAGCCTGGGTTGAGTATATCCCGTACCACTTCC 
               
               
                   
               
               
                   
                 GCCCTAACTACCATGGTGTGGGTACTTGCTCCATG 
               
               
                   
               
               
                   
                 ATGCCGAAGGAGATGGGCGGTGTTGTCGACAATGC 
               
               
                   
               
               
                   
                 TGCCCGTGTGTATGGTGTGCAGGGACTGCGAGTCA 
               
               
                   
               
               
                   
                 TCGATGGTTCTATTCCCCCTACGCAGATGTCGTCC 
               
               
                   
               
               
                   
                 CATGTTATGACGGTCTTTTATGCCATGGCCTTAAA 
               
               
                   
               
               
                   
                 GATTGCGGATGCCGTCTTGGCGGATTACGCTTCTA 
               
               
                   
               
               
                   
                 TGCAGTAAGAGGAAGA 
               
               
                   
               
               
                   
                 GOD-M5-A 
               
               
                   
                 SEQ ID NO: 21 
               
               
                   
                 SNGIEASLLTDPKEVAGRTVDYIIAGGGLTGLTVA 
               
               
                   
               
               
                   
                 ARLTENPDITVLVIESGCYESDRGPIIEDLNAYGD 
               
               
                   
               
               
                   
                 IFGSSVDHAYETVCLATNNQTALIRSGNGLGGSTL 
               
               
                   
               
               
                   
                 VNGGTWTRPHKAQVDSWETVFGNEGWNWDSVAAYS 
               
               
                   
               
               
                   
                 LQAERARAPNAKQIAAGHYFNASCHUNGTVHAGPR 
               
               
                   
               
               
                   
                 DTGDDYSPIVKALMSAVEDRGVPTKKDLGCGDPHG 
               
               
                   
               
               
                   
                 VSMFPNTLHEDQVRSDAAREWLLPNYQRPNLQVLC 
               
               
                   
               
               
                   
                 GQYVGKVLLSQNATTPRAVGVEFGTHKGNTHNVYA 
               
               
                   
               
               
                   
                 KHEVLLAAGSAVSPTILEYSGIGMKSILEPLGIKT 
               
               
                   
               
               
                   
                 VVDLPVGLNLQDQTTSTVRSRITSAGAGQGQAAWF 
               
               
                   
               
               
                   
                 ATFNETFGDYTEKAHELLNTKLEQWAEEAVARGGF 
               
               
                   
               
               
                   
                 HNTTALLIQYENYRDWIVKDNVAYSELFLDTAGEA 
               
               
                   
               
               
                   
                 SFDVWDLLPFTRGYVHILDKDPYLRHFAYDPQYFL 
               
               
                   
               
               
                   
                 NELDLLGQAAATQLARNISNSGAMQTYFAGETIPG 
               
               
                   
               
               
                   
                 DNLAYDADLRAWVEYIPYHFRPNYHGVGTCSMMPK 
               
               
                   
               
               
                   
                 EMGGVVDNAARVYGVQGLRVIDGSIPPTQMSSHVM 
               
               
                   
               
               
                   
                 TVFYAMALKIADAVLADYASMQ 
               
               
                   
               
               
                   
                 GOD-M5-B 
               
               
                   
                 SEQ ID NO: 22 
               
               
                   
                 GAATTCAGCAATGGAATTGAAGCAAGCCTCCTGAC 
               
               
                   
               
               
                   
                 TGACCCCAAGGAGGTTGCCGGCCGCACTGTCGACT 
               
               
                   
               
               
                   
                 ACATCATCTGCGGTGGAGGTCTGACTGGACTCACC 
               
               
                   
               
               
                   
                 GTCGCTGCCCGTCTGACGGAGAACCCCGATATCAC 
               
               
                   
               
               
                   
                 TGTGCTTGTCATCGAAAGTGGCTCCTACGAGTCTG 
               
               
                   
               
               
                   
                 ACAGAGGTCCTATCATTGAGGACCTGAACGCTTAC 
               
               
                   
               
               
                   
                 GGTGACATTTTTGGCAGCAGTGTGGACCACGCCTA 
               
               
                   
               
               
                   
                 CGAGACTGTCTGCCTCGCCACCAACAATCAGACTG 
               
               
                   
               
               
                   
                 CGCTGATCCGCTCCGGAAATGGTCTCGGTGGCTCT 
               
               
                   
               
               
                   
                 ACCCTCGTCAACGGTGGCACCTGGACTCGCCCCCA 
               
               
                   
               
               
                   
                 CAAGGCACAAGTTGACTCATGGGAGACCGTCTTCG 
               
               
                   
               
               
                   
                 GAAATGAGGGCTGGAACTGGGACAGCGTGGCCGCC 
               
               
                   
               
               
                   
                 TACTCCCTCCAGGCTGAGCGTGCTCGCGCACCAAA 
               
               
                   
               
               
                   
                 TGCCAAACAGATTGCTGCTGGCCACTACTTTAATG 
               
               
                   
               
               
                   
                 CATCCTGCCATGGTATCAATGGTACTGTCCACGCC 
               
               
                   
               
               
                   
                 GGACCCCGCGATACCGGTGATGACTACTCCCCCAT 
               
               
                   
               
               
                   
                 CGTCAAGGCTCTCATGAGCGCTGTCGAAGACAGGG 
               
               
                   
               
               
                   
                 GCGTTCCCACCAAGAAGGACTTGGGATGCGGTGAC 
               
               
                   
               
               
                   
                 CCCCATGGTGTGTCCATGITCCCCAACACCTTGCA 
               
               
                   
               
               
                   
                 CGAAGACCAAGTGCGCTCTGATGCCGCTCGCGAAT 
               
               
                   
               
               
                   
                 GGCTCCTCCCCAACTACCAGCGTCCCAACCTGCAA 
               
               
                   
               
               
                   
                 GTCCTCACTGGACAGTATTGCGGAAAGGTCCTGCT 
               
               
                   
               
               
                   
                 CAGCCAGAACGCTACCACACCTCGTGCCGTTGGCG 
               
               
                   
               
               
                   
                 TGGAATTCGGCACCCACAAGGGCAACACCCACAAC 
               
               
                   
               
               
                   
                 GTCTACGCTAAGCACGAGGTCCTCCTGGCCGCTGG 
               
               
                   
               
               
                   
                 ATCCGCTGTCTCTCCCACCATCCTCGAATATTCCG 
               
               
                   
               
               
                   
                 GTATCGGAATGAAGTCCATTCTAGAGCCTCTTGGA 
               
               
                   
               
               
                   
                 ATTAAGACCGTCGTTGACCTGCCCGTTGGTCTCAA 
               
               
                   
               
               
                   
                 CCTTCAGGACCAGACCACCTCTACCGTCCGCTCAC 
               
               
                   
               
               
                   
                 GCATTACCTCCGCCGGTGCCGGACAGGGACAGGCC 
               
               
                   
               
               
                   
                 GCTTGGTTCGCTACCTTCAACGAGACCTTTGGCGA 
               
               
                   
               
               
                   
                 CTACACCGAAAAGGCTCACGAGCTGCTCAACACCA 
               
               
                   
               
               
                   
                 AGCTGGAGCAGTGGGCCGAAGAGGCCGTCGCCCGT 
               
               
                   
               
               
                   
                 GGCGGATTCCACAACACCACCGCTTTGCTCATCCA 
               
               
                   
               
               
                   
                 GTACGAGAACTACCGCGACTGGATCGTCAAGGACA 
               
               
                   
               
               
                   
                 ATGTCGCATACTCGGAACTCTTCCTCGACACGGCC 
               
               
                   
               
               
                   
                 GGAGAAGCCAGTTTCGATGTGTGGGATCTTCTGCC 
               
               
                   
               
               
                   
                 CTTCACTAGAGGATACGTCCACATCCTCGACAAGG 
               
               
                   
               
               
                   
                 ACCCCTACCTCCGCCATTTCGCCTACGACCCTCAG 
               
               
                   
               
               
                   
                 TACTTCCTCAACGAGCTTGACCTGCTCGGCCAGGC 
               
               
                   
               
               
                   
                 TGCCGCCACTCAGCTGGCCCGCAACATCTCTAACT 
               
               
                   
               
               
                   
                 CCGGTGCCATGCAAACTTATTTCGCTGGAGAGACT 
               
               
                   
               
               
                   
                 ATTCCCGGTGACAACCTCGCGTATGATGCCGACTT 
               
               
                   
               
               
                   
                 GAGAGCCTGGGTTGAGTATATCCCGTACCACTTCC 
               
               
                   
               
               
                   
                 GCCCTAACTACCATGGTGTGGGTACTTGCTCCATG 
               
               
                   
               
               
                   
                 ATGCCGAAGGAGATGGGCGGTGTTGTCGACAATGC 
               
               
                   
               
               
                   
                 TGCCCGTGTGTATGGTGTGCAGGGACTGCGAGTCA 
               
               
                   
               
               
                   
                 TCGATGGTTCTATTCCCCCTACGCAGATGTCGTCC 
               
               
                   
               
               
                   
                 CATGTTATGACGGTCTTTTATGCCATGGCCTTAAA 
               
               
                   
               
               
                   
                 GATTGCGGATGCCGTCTTGGCGGATTACGCTTCTA 
               
               
                   
               
               
                   
                 TGCAGTAAGAGGAAGA 
               
               
                   
               
               
                   
                 GOD-M5-B 
               
               
                   
                 SEQ ID NO: 23 
               
               
                   
                 SNGIEASLLTDPKEVAGRTVDYIICGGGLTGLTVA 
               
               
                   
               
               
                   
                 ARLTENPDITVLVIESGSYESDRGPIIEDLNAYGD 
               
               
                   
               
               
                   
                 IFGSSVDHAYETVCLATNNQTALIRSGNGLGGSTT 
               
               
                   
               
               
                   
                 LVNGGTWTRPHKAQVDSWETVFGNEGWNWDSVAAY 
               
               
                   
               
               
                   
                 SLQAERARAPNAKQIAAGHYFNASCHGINGTVHAG 
               
               
                   
               
               
                   
                 PRDTGDDYSPIVKALMSAVEDRGVPTKKDLGCGDP 
               
               
                   
               
               
                   
                 HGVSMFPNTLHEDQVRSDAAREWLLPNYQRPNLQV 
               
               
                   
               
               
                   
                 LTGQYCGKVLLSQNATTPRAVGVEFGTHKGNTHNV 
               
               
                   
               
               
                   
                 YAKHEVLLAAGSAVSPTILEYSGIGMKSILEPLGI 
               
               
                   
               
               
                   
                 KTVVDLPVGLNLQDQTTSTVRSRITSAGAGQGQAA 
               
               
                   
               
               
                   
                 WFATFNETFGDYTEKAHELLNTKLEQWAEEAVARG 
               
               
                   
               
               
                   
                 GFHNTTALLIQYENYRDWIVKDNVAYSELFLDTAG 
               
               
                   
               
               
                   
                 EASFDVWDLLPFTRGYVHILDKDPYLRHFAYDPQY 
               
               
                   
               
               
                   
                 FLNELDLLGQAAATQLARNISNSGAMQTYFAGETI 
               
               
                   
               
               
                   
                 PGDNLAYDADLRAWVEYIPYHFRPNYHGVGTCSMM 
               
               
                   
               
               
                   
                 PKEMGGVVDNAARVYGVQGLRVIDGSIPPTQMSSH 
               
               
                   
               
               
                   
                 VMTVFYAMALKIADAVLADYASMQ