CN106916836B - Biosynthetic gene cluster of compounds and application thereof - Google Patents

Biosynthetic gene cluster of compounds and application thereof Download PDF

Info

Publication number
CN106916836B
CN106916836B CN201511000174.9A CN201511000174A CN106916836B CN 106916836 B CN106916836 B CN 106916836B CN 201511000174 A CN201511000174 A CN 201511000174A CN 106916836 B CN106916836 B CN 106916836B
Authority
CN
China
Prior art keywords
gene
encodes seq
seq
encodes
cluster
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201511000174.9A
Other languages
Chinese (zh)
Other versions
CN106916836A (en
Inventor
刘然
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Wuhan Hesheng Technology Co ltd
Original Assignee
Wuhan Hesheng Technology Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Wuhan Hesheng Technology Co ltd filed Critical Wuhan Hesheng Technology Co ltd
Priority to CN201511000174.9A priority Critical patent/CN106916836B/en
Publication of CN106916836A publication Critical patent/CN106916836A/en
Application granted granted Critical
Publication of CN106916836B publication Critical patent/CN106916836B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/52Genes encoding for enzymes or proenzymes
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/36Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Actinomyces; from Streptomyces (G)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/0004Oxidoreductases (1.)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10Transferases (2.)
    • C12N9/1003Transferases (2.) transferring one-carbon groups (2.1)
    • C12N9/1007Methyltransferases (general) (2.1.1.)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10Transferases (2.)
    • C12N9/1025Acyltransferases (2.3)
    • C12N9/1029Acyltransferases (2.3) transferring groups other than amino-acyl groups (2.3.1)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10Transferases (2.)
    • C12N9/1048Glycosyltransferases (2.4)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10Transferases (2.)
    • C12N9/12Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/24Hydrolases (3) acting on glycosyl compounds (3.2)
    • C12N9/2402Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
    • C12N9/2405Glucanases
    • C12N9/2434Glucanases acting on beta-1,4-glucosidic bonds
    • C12N9/2437Cellulases (3.2.1.4; 3.2.1.74; 3.2.1.91; 3.2.1.150)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/88Lyases (4.)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/90Isomerases (5.)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12PFERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P17/00Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/18Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
    • C12P17/181Heterocyclic compounds containing oxygen atoms as the only ring heteroatoms in the condensed system, e.g. Salinomycin, Septamycin
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y203/00Acyltransferases (2.3)
    • C12Y203/01Acyltransferases (2.3) transferring groups other than amino-acyl groups (2.3.1)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y207/00Transferases transferring phosphorus-containing groups (2.7)
    • C12Y207/13Protein-histidine kinases (2.7.13)
    • C12Y207/13003Histidine kinase (2.7.13.3)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y302/00Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
    • C12Y302/01Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
    • C12Y302/01004Cellulase (3.2.1.4), i.e. endo-1,4-beta-glucanase
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y303/00Hydrolases acting on ether bonds (3.3)
    • C12Y303/02Ether hydrolases (3.3.2)
    • C12Y303/02003Epoxide hydrolase (3.3.2.3)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y402/00Carbon-oxygen lyases (4.2)
    • C12Y402/01Hydro-lyases (4.2.1)
    • C12Y402/01046Hydro-lyases (4.2.1) dTDP-glucose 4,6-dehydratase (4.2.1.46)

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Medicinal Chemistry (AREA)
  • Biophysics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

The invention discloses a biosynthetic gene cluster of a compound and application thereof. Wherein, a biosynthetic gene cluster of a compound, said biosynthetic gene cluster comprising: the I type linear polyketide synthase gene module comprises: 3a1 gene, 3a2 gene, 3A3 gene, 3a4 gene, 3a5 gene, 3a6 gene, 3a7 gene, 3A8 gene, 3a9 gene, 3a10 gene and 3a11 gene; a glycosyl synthesis-associated gene module comprising: 3G1 gene, 3G2 gene, 3G3 gene, 3G4 gene, 3G5 gene, 3G6 gene, 3G7 gene, 3G8 gene, 3M gene, and 3G9 gene; and a modifier gene module comprising: 3O gene, 3I gene, 3E gene, 3P1 gene, 3P2 gene and 3P3 gene.

Description

Biosynthetic gene cluster of compounds and application thereof
Technical Field
The invention relates to the field of bioengineering, in particular to a biosynthetic gene cluster of a J1001-3 compound and application thereof, and more particularly relates to a biosynthetic gene cluster of the J1001-3 compound, a microorganism and a method for preparing the J1001-3 compound.
Background
Polyketides are one of the most abundant groups of natural products, and are widely applied to the fields of medical use, veterinary use, agriculture and the like due to the great medicinal value of the polyketides. Such as the antibiotic erythromycin, the antiparasitic antibiotic abamectin, etc. Polyketides are formed under the catalysis of polyketide synthase (PKS), and gene clusters assembled in a modular form determine the structure and thus the biological activity of the polyketides, so that the gene cluster of a new compound has great significance for the subsequent research.
With the increasing severity of the drug resistance problem of pathogenic bacteria, the clinical need for new antibiotics is more urgent. In order to deal with the situation, people improve the existing antibiotics on one hand and accelerate the step of screening novel antibiotics on the other hand. The J1001-3 compound is a recently discovered antibiotic, encoding good bacteriostatic activity.
To date, no study related to the biosynthesis gene cluster of the J1001-3 compound has been reported.
Disclosure of Invention
The present invention is directed to solving at least one of the problems of the prior art. To this end, it is an object of the present invention to propose a biosynthetic gene cluster encoding antibiotic-J1001-3 compounds with antibacterial activity.
According to one aspect of the present invention, the present invention provides a biosynthetic gene cluster of a J1001-3 compound, wherein the J1001-3 compound has the following structure,
Figure BDA0000889460040000011
according to an embodiment of the invention, the biosynthetic gene cluster comprises:
the I type linear polyketide synthase gene module comprises: 3a1 gene, 3a2 gene, 3A3 gene, 3a4 gene, 3a5 gene, 3a6 gene, 3a7 gene, 3A8 gene, 3a9 gene, 3a10 gene and 3a11 gene;
a glycosyl synthesis-associated gene module comprising: 3G1 gene, 3G2 gene, 3G3 gene, 3G4 gene, 3G5 gene, 3G6 gene, 3G7 gene, 3G8 gene, 3M gene, and 3G9 gene; and
a modifier gene module comprising: 3O gene, 3I gene, 3E3E gene, 3P1 gene, 3P2 gene and 3P3 gene.
The inventors have surprisingly found that the biosynthetic gene cluster of the J1001-3 compounds of the examples of the invention can control the biosynthesis of the J1001-3 compounds.
According to an embodiment of the invention, the 3a1 gene encodes SEQ ID NO: 1; the 3A2 gene encodes SEQ ID NO: 2; the 3A3 gene encodes SEQ ID NO: 3; the 3A4 gene encodes SEQ ID NO: 4; the 3A5 gene encodes SEQ ID NO: 5; the 3A6 gene encodes SEQ ID NO: 6; the 3A7 gene encodes SEQ ID NO: 7; the 3A8 gene encodes SEQ ID NO: 8; the 3A9 gene encodes SEQ ID NO: 9; the 3A10 gene encodes SEQ ID NO: 10; the 3A11 gene encodes SEQ ID NO: 11, or a pharmaceutically acceptable salt thereof.
According to an embodiment of the invention, the 3G1 gene encodes SEQ ID NO: 12; the 3G2 gene encodes SEQ ID NO: 13; the 3G3 gene encodes SEQ ID NO: 14; the 3G4 gene encodes SEQ ID NO: 15; the 3G5 gene encodes SEQ ID NO: 16; the 3G6 gene encodes SEQ ID NO: 17; the 3G7 gene encodes SEQ ID NO: 18; the 3G8 gene encodes SEQ ID NO: 19; the 3M gene encodes SEQ ID NO: 20; the 3G9 gene encodes SEQ ID NO: 21, or a pharmaceutically acceptable salt thereof.
According to an embodiment of the invention, the 3O gene encodes SEQ ID NO: 22; the 3I gene encodes SEQ ID NO: 23; the 3E gene encodes SEQ ID NO: 24; the 3P1 gene encodes SEQ ID NO: 25; the 3P2 gene encodes SEQ ID NO: 26; the 3P3 gene encodes SEQ ID NO: 27, or a pharmaceutically acceptable salt thereof.
According to an embodiment of the present invention, the biosynthetic gene cluster further comprises: a regulatory gene module comprising: 3R1 gene, 3R2 gene, 3R4 gene, 3T1 gene, 3T2 gene, 3T3 gene, 3T4 gene and 3T5 gene.
According to an embodiment of the invention, the 3R1 gene encodes SEQ ID NO: 28; the 3R2 gene encodes SEQ ID NO: 29; the 3R4 gene encodes SEQ ID NO: 30; the 3T1 gene encodes SEQ ID NO: 31; the 3T2 gene encodes SEQ ID NO: 32; the 3T3 gene encodes SEQ ID NO: 33; the 3T4 gene encodes SEQ ID NO: 34; the 3T5 gene encodes SEQ ID NO: 35.
According to the embodiment of the present invention, along the 5 '-3' end of the gene, said 3T3 gene, said 3T4 gene, said 3T5 gene, said 3R1 gene, said 3R2 gene, said 3A1 gene, said 3A2 gene, said 3A3 gene, said 3A4 gene, said 3A5 gene, said 3A6 gene, said 3P1 gene, said 3G5 gene, said 3M gene, said 3G4 gene, said 3G1 gene, said 3G9 gene, said 3A7 gene, said 3E gene, said 3A10 gene, said 3O gene, said 3I gene, said 3P2 gene, said 3A9 gene, said 3A11 gene, said 3A8 gene, said 3P3 gene, said 3R4 gene, said 3G6 gene, said 3G7 gene, said 3G8 gene, said 3T1 gene, and said T2 gene are connected in series.
According to an embodiment of the invention, the biosynthetic gene cluster encodes SEQ ID NO: 36.
According to another aspect of the present invention, there is provided a microorganism. According to an embodiment of the invention, the microorganism encodes the aforementioned biosynthetic gene cluster. The inventors have surprisingly found that the J1001-3 compound can be synthesized efficiently, simply and at low cost by performing a fermentation treatment using the microorganism.
According to an embodiment of the invention, the microorganism is streptomyces.
According to yet another aspect of the present invention, there is provided a process for preparing a compound of J1001-3. According to an embodiment of the invention, the method comprises: carrying out fermentation treatment by using the microorganism so as to obtain the fermented microorganism; carrying out wall breaking treatment on the fermented microorganisms to obtain a solution containing the J1001-3 compound; and purifying the J1001-3 compound from the solution containing the J1001-3 compound so as to obtain a pure product of the J1001-3 compound.
According to the method for preparing the J1001-3 compound of the embodiment of the invention, the J1001-3 compound can be efficiently synthesized by performing fermentation treatment using the aforementioned microorganism. Then, the pure J1001-3 compound can be obtained efficiently, simply and at low cost through microbial wall breaking treatment and separation and purification treatment.
Additional aspects and advantages of the invention will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the invention.
Drawings
The above and/or additional aspects and advantages of the present invention will become apparent and readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings of which:
FIG. 1 shows a schematic diagram of the sequence of biosynthetic gene cluster for the J1001-3 compound according to one embodiment of the present invention;
FIG. 2 shows a schematic flow diagram of a process for preparing a J1001-3 compound according to one embodiment of the present invention;
FIG. 3 shows a schematic flow diagram of the biosynthetic pathway of the J1001-3 compound according to one embodiment of the present invention;
FIG. 4 shows a schematic map of a J1001-3 compound according to one embodiment of the present invention.
Detailed Description
Reference will now be made in detail to embodiments of the present invention, examples of which are illustrated in the accompanying drawings, wherein like reference numerals refer to the same or similar elements throughout, or elements encoding the same or similar functions. The embodiments described below with reference to the accompanying drawings are illustrative only for the purpose of explaining the present invention, and are not to be construed as limiting the present invention.
In the description of the present invention, the terms "longitudinal", "lateral", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", and the like indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings, which are for convenience of description of the present invention only and do not require that the present invention must be constructed and operated in a specific orientation, and thus, should not be construed as limiting the present invention.
It should be noted that the terms "first" and "second" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or to implicitly indicate the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. Further, in the description of the present invention, "a plurality" means two or more unless otherwise specified.
According to one aspect of the present invention, there is provided a biosynthetic gene cluster of the J1001-3 compound. According to an embodiment of the present invention, the biosynthetic gene cluster includes:
the I type linear polyketide synthase gene module comprises: 3a1 gene, 3a2 gene, 3A3 gene, 3a4 gene, 3a5 gene, 3a6 gene, 3a7 gene, 3A8 gene, 3a9 gene, 3a10 gene and 3a11 gene;
a gene module associated with glycosyl synthesis, the gene module comprising: 3G1 gene, 3G2 gene, 3G3 gene, 3G4 gene, 3G5 gene, 3G6 gene, 3G7 gene, 3G8 gene, 3M gene, and 3G9 gene; and
a modifier gene module comprising: 3O gene, 3I gene, 3E gene, 3P1 gene, 3P2 gene and 3P3 gene.
The inventors have surprisingly found that the biosynthetic gene cluster of the J1001-3 compounds of the examples of the invention can control the biosynthesis of the J1001-3 compounds.
According to an embodiment of the present invention, the biosynthetic gene cluster (also referred to as simply "gene cluster" in the present invention) is a biosynthetic gene cluster of streptomyces, encoding the amino acid sequence of SEQ ID NO: 36, specifically as follows:
GTGGTGCGCGCGGGCATCTCGGCGTGGTGTGCCGCCGCCGACGCGCCGATCAAGGTGGTGGCTGAGGGGGCGAACGTGTCGGTGGCGCTCCACGGGCCGGGGCGGGGGGCGGATGTCGTGGTCATGGATCTGCTGTTGCAGAACGGGCGGCCCGCGTACGACGAGCTGCAGGAGCTCGTGGCCCAGGAGCGCAAGGTCGTGGTGTATACCATGCGGGACAGCCAGGAGGCGGCGTTGACCTGCATGGATCTGGGGTCGGCCACCTACATCACCAAGGCGGAGGGGCAGCGGCACCTGGTCAAGGCGATCCGGGCCGCCGCTGAGGACATCCCCTATACGCCCCCGTCGCTGGCCGGCGCCTTCGGCAGCGACACCCGGCAGAGCCGGCCCGTGCTGTCCGTACGGGAGGTGGAGGTGCTGGTGGAGTGGTTCCAGTCGGAGTCGAAGGCCGTGGTCGCCCAGAGCCTGGGGATCTCCGAGCGCACGGTGAACACCTACCTGGACCGGGTGCGCATCAAGTACGCGAACGCCGGCCGCCCGGCGACCACGAAGGCCAAACTGGTGGCCAGGGCGGTTCAGGACGGGCTGATAGCTCTGGACGAGCTGTGATCCGGCACGCGGCCTCCACGAGGAGACGGTCCTCGGCGTGGACCGTGCGCACCCGGATCCCGTTGGCCGCGGGCGCGGGCGGCCGGTCCTGCAGCGCGTCCACCACGATGCCCACCCGCACCTGATCCCCGCCGCGGACGACGGTGACGCGCGCCGTCTGCCCGGCGGCGGCGAGGGCGGCGATGACCGGGTCCAGGAGCGCGCGGCGCAGGGGCAGCGGCAGTTCGAGGGGGTCGCCGCGGACGGCGAGTTGCACGGTGGTGCCGTTGCGCTCGGCGACGTCGATGCAGGCGCGCATCTCGTGGACCAGCGGGTCGAACGTACAGTCGCTCTCCGCGAACAGCCGCCTCAGCCGGGCGGCTTCCAACGCGCAGGCGCGCCGCACCTCGTCGTCCTCCGGGTCGAGGGAGCCGCTGGCGAGGCCGGTGAGCAGGGGGAGCACGGTGGTGTTCAGCTCGGCGTACCGGCGGCGCTGGTCCGCCTGGATCTGCCGGGCGACGGCGATACGGGTGCGCACCCGCTCCTGGGCCCGCAGGGCCTCGCCGATGGCTCTGCTGCTGTCGAGGAGGAGCTTCGCGCCGGCGGCGATGATCATCTGGAAGCAGCAGGCGGAGAGGACGCTCAGGGCCATGCTCGCTCCGGTGTGCCGCGAGGGCACCTGGACCGTCAGCAACAGGGCGCCGGTGACGGCCAGATGGCAGCCGAGGAAGACGCCGGAGACCACCGGCCCCCGGTCGGCGAGCAGGACGACGGCGAACCAGCCCGCGAGGGAGTAGGACCAGTGGGAGGTGGTGAGGAAGTAATGGTCCGCCGGGACCTGGGTGGTGGTGGCCACCGAGGCCGCGAAGACGCCGGTCAGCGCCGCCGGCACCCAGCCGCGCGGCCATGGGCGCCCGTCGAGGCCGAGGACGACGCTGCCGCCGAGGACCAGCGTGAGCAGTCCGTAGGCGGCGAGGGGGACAAAGGGGTGCCGGTAGTCGTCCAGAGCGCCGAGCAGGCCGGGCAGGGCGGCCCCGATGTGGAGGGTGACCAGGATGAGCAGCCCCCCGACGCGGATGCCGCGGAGCTGATGACGGGTGATCAGCTGACGGAAGTCCTCACCCACGCGGCCACTCCAGCCGCACCGTCGTACCGTGTCCGGGCCGGGACTCCACCGTGGCGCGGCCCCCCACGTTCCACATCCGTCCGCGGATCGAACGCTTGATCCCGATCCGCTGGGTGGGGATGCGCTCGGGGTCGAACCCCACCCCGTGGTCGGCGATGGTCACGACGATCACCTCCCCCGCGCGGTGCGCCGTCACCCGTACGACCTCGACGCCCGCGTAGCGGGCCACGTTGCGCAGCGCCTCGCCGAGACCGCCGCGCAGGGCCGCCGCGACGGGGCGCCAGGCCGTGCCCAGGTCCTCGTCGAATCTGCTGATGACGCGGAGGGGGTGCGCGACGATCTCGTCCAGCAGTTCGGCGGCCAGGTCCACCTCCCCCGCCACCGGCTGCTCGGCGCGCAGCCGCACGAGGTCTCTGGCGGCCTGGGCCCGCAGTGTCTCGGTCCGCATCGACGCCCACGGCGCCGACGCGATCAGCAGGGTCGCGCAGGCGGTGTCATGGAGCGCGGCCAGGTGCTCCCGCTCCGCGGCGCAGCGGGCCTCCGCCGCCTCCCCGTGCCGCCGTGCCCGCGCGGCCCGGTCGGCGGCGTCGTCGGCCGCCCGGCTCTCGCTGAACACCAGCCGGACCACGGCCCGGGCCAGGACGGTGTTCACCACCACCCAGATGACACTGCGCAGCACGCCGGGCCACTGGAGGTGCGGGTGCAGCGCGGCGCCCACCACATCCGCGCAGCACAGCCACAGCGTCGCCAGCATCGCGGTGCGCAGCGGCTGCATCAGCTGGTACGCCACGGCCGTGAAGTTGACGCACACCATGACCCATGTGCCCCCGTGCGTGGTCTGCGTCTCGGGGATGGTGAACCGCTGGCTCAGACACAGCGCCGTCATGACCGCCAGGTCCAGGGTGAGCAGCGACCTCGGCGGCATCGCCGGGGTGGTGGCCAGCCGCAGGTGGATCCAGCTCCAGGCGAGCACGGCCGCCGCGACCACCGCCGTGGGCGCCATCTCGTCCACCGGCATGGCCACCACGCCCAGCACGGCGCACGCGCTCATCACCCCGGCGCGCCCGTAGAGCGCCAACCGCCGGTTGAACGCGACGTATTCACGCGCCCAGGGCCCTCCCGAGCCGGGAAGGCGCGCCGCGGCCGGCGGGTCGATACCGGGCGACAGTGAGCGAATCGGCATGGGCATCCATCCTCGGCGGCCATCGATGTGGCGGGGCGGTAGAGGTGACCTCACGATCCGTGAGGAAATCGAAGCCTTTTGTCGGTCGAACGACCCTCACACCGGAGGACCCGGCGCGTCTAGGCTGGACCGAGCGCAGTGGCTTGGGGGCGCAGATCGGGATGATCT GGAAGCCCGCCCACGTCGGGCCCCCACAAGCCCTTTGCGAGCAAGAAGTATGCCGCCCATCGGCGCGCTTTCCGCCTCATGCCAACCTTCTCTTGGGTGTATAGCGAAGGGAATGCAGCCTTTTATGTCCGCATCTGCGCCCAATGTCATCCTGCTCGGCGGCCCCACGGAGCTGGCCGATCCGCACACCCGGTACGTCGATGACACCGAGTCGACCCTGAAGCTCCTCATCGGCAACGCGTACGAACACTTCGAGCCCACAGGCCAGTTCATGGAGCACCACGGGCGGCATCTGCGGGTCTTCGAGTGGATCCGCCGGACGTATGTCGCCGAGTAATCAGCCACGCGGCCAGGGCCCGGTCTTCGCCGGCGGGTTCACTCGCAGATGTGCGAGTCGAACCCCCGGCGAGCTCGGGCGGTGGCCTGCAGAACGAGTCCGCCAGGCGCGGTCCGTCAGGTCGAGGCGAGAACCGTGTGCCGGAGCTCCCTGAGTTTCCGGCCGGGTTCAAGCCCCAGTTCCCTGTCGAGAACACGTCTGGCGGACTCGTATATGCCAAGCGCCTCGGACTTCCGGTCGGAGCGGTAGAGGGCCAGCATCAGCTGTCGGTAGAACGTCTCCCGGAGCGGGAACTCGGCGACGAGGGAGTGCAGCCGGCCGACGAGTTCCCGATGGCGGCCGAGTTCGAGATACGCCTCGGCCGACATCTCAGCACATTCAATACGCATCTCGTCCAGCCGCTTAAGAAAACCGGTCACGATCGGTCCCGTCTGGACATTCCCGAACGCCGGGCCCCGCCACAGCGCCAGGGCCTGTTCGAAACACAGCGCCGCCTGCGCGGGCTCCTCGTATCTGACGTACTTCCGCCCGTCGGTGACCAGCTGCTGGAAGGCGTCGAAATCGCATTCGCTCGACGCCCTGCGCAGCATATATCCACCCGGGCGGGTGATGATGGGATTCTGCTGGCCCGAACGGCTCAGGAACTTGCGCAGCCGCGAAATGCAGACGTAGATACTCGCGGTGTCGCGCCGAGGCGGCAGCTCGCCCCAGATCTCTCTGGTGAGCTGTTCCGCCATCACGACCTGATCCGAGCGGATCAGCAGGACGGCGAGAACGGTAGCGAGTTTCTGCGCTCTGAGCGGCGAACCGCCCTTTTCGTCGACTACACGGAGAGGTCCCAAAATCTCGTACCGCACGAATTACCCCCTGTTCTGCTGTTCCTGGATGCGTGACGAGTCGGCGGTGCGCGCGATTCGGCTAGGCGGCTTCGAGTTCCGGGGCGTCGATGAGCACGGCATGGTGCAACCGCTTGAGGGCGGCGGACGGCTCAAGCCCGAGTTCCTCGCTCAGCACGGTCCGCGCCGACTGGTAGACACTCAGGGCGTCGGCCCTGCAGCCCGAACGGTAGAGCGCCAGCATGAGCTGCCGGTAGAACGCCTCGTTCAGCGGAAGCTCCTCTATCCGGGCGTAGAGGTAGCTGACGAACTCACGGTGGCGGCCGAGCTCCAGGCCGGCGTCCACGAACGACTCGACGCATTCCAGCCGGGCCTGCTCGGCCCAGCACACGAAGCCGTTGACGATCGCCCCGTCGCGCAGGTCCTCGAGGACCGGGCCGCGCCAGAGGTCAAGGCCCTCTTCGTAAGCCTCGCAGGCCTCATGGGTGCGCCCGGCCCGCTGTGCGGCCCGCCCCTGGCGCACCAGCCCCTGGAAGACATGGAAGTCCAGCTCGTCCGCGCCGAGACGCAGCACATACCCGCTGCGAGCGGTCACGATGGGGCTCTCGGTGCGGTTGGGGCGCCTGAGGAACTTGCGGAGTTGGGACACATAGACGTGGAGCGCCGCCACGGCCTGCCGCGGCGCCCGGGTGCCCCAGATCTCCTTCACCAGATCTTCGCTGCTCACCACCTCGTCGGCCCGCACGAGTAATGCCGCCAGCAGCACCTCGATCTTGCGGGCACTGATTGAGGTGACCGAAGATCCGTCAACCACGCGCAACGGGCCCAGTATCTCGTACCTCATGATACGCGAACTCCCCCCATCGCCGGCGTCGTGTCGAACCAGGAGTGCGCTCCATTGTGATCGAATTCGGCCAGCATCCGAAAAATTCACCCCGATTTTGGAAGCCTTTATGGTCGCGCTTCAGACCTCAGCGTCGATGCCTACCCACGCCACCGACAGCTTAGCCAGATCGCAGCCACCTCCGCGCATTTCACATGGCTGCAACATCGCCCCCAGTGAGGTTTTCGGTCAGATGGGAGGTGGTCTTCTGGCTACGGAGATCGACGGCGTTGCTCTGCGATCGACGGCTGCGCCGACTCATGGTGCCGAACTGCGCCCGGCATCACGGGCCGCGGTCCTCTCCGAAGGGCGAACAACCAGCAGCAGTGATCGCAGAGAGGGCAACATCAACGCATCCTAACTGTGCGGCGCGCGCCAGTGTGAGGGTCAATAGACCCACAACCAAATCGGCACATAGGGTGATTCGTCGATCGGTGACCGTCACCGTACCCTGCCGTTTCGGTGGCGGCCCCACGCAGGTCACCGCTCTGATCCGAAGCATCAGCGGGTCAAGTTTCGCCCGGCGTATACAAGGAGCTCCCCAGACATTCCCGGTTAGATCAACTTTAGAAAACATTCGGAGAATGAGCGCTGTTCGGGGCATCTCGTAAGCCATAGCCAGCGGTTTCGCGATTCAGGTATGGGGGTGTCATGGCCGGGAGCAGCCCGAGCCACGCGCAGCAGGCGGCGTCTCCCGTCGCGATCGTGGGGCTGGCCTGCCGGCTGCCCGGCGCACCCGATCCCGAGGCGTTCTGGCGCCTGCTGCGCGCGGGCGAGAACGCCGTCGTCCCGGTCCCGGACGACCGCCTGTCCGCCGAGCCCGGTTCCGCGCCGTACTTCGCCGGGCTACTGGAGCACATCGACACCTTCGACGCCGGATTCTTCGGCATCTCGCCGCGCGAGGCCACGGCGATGGATCCGCAGCAGCGGCTGATGCTCGAACTGGCCTGGGAGGCCATGGAGGACGCGGGGCTCGGCCCCGGGAACCTTGCGGGGTGCCGGACCGCGGTGTTCACCGGCGCGATCTGGGACGACTACGCCACGCTCCTCCACCGGCACGGGCCCAGCGACATCGCCATCACCCGGCACACGATGGCGGGCCTGCACCGCGGCATCATCGCCAACCGGATATCCCACCTCCTGGGCCTGCGCGGCCCGAGCCTCACGGTGGACGCGGCGCAGTCCTCCGGGCTCGTCGCCGTACACCTGGCCTGCGAGAGTCTGCGCCGCAGGGAGGCGGATCTGGCGCTCGCGGGCGGGGTGAACCTGATCCTGGCCGAGGAGAGCATGCGGATGGCGAAGGCCCAGTTCCAGGGCCTGTCGCCGGACGGCCGGTGCTACACCTTCGACGCGCGCGCCAACGGCTTCGTACGCGGCGAGGGCGGCGGAATGGTGCTGCTCAAGCCGCTGGCCGCGGCCGTCGACGACGGCGACCCGGTGTACTGCGTGATCGAGGGCAGCGCGGTCAACAACGACGGCGCCACCGACGGCCTGACCCGGC CGAGCGCCGAGGCCCAGACGGATGTGGTGCGGCAGGCGTGGCGGCGGGCCGCGGTGTCGCCCGCCGAACTCCAGTACGTCGAACTGCACGGCACCGGCACACCGGTCGGCGATCCGACCGAGGCCGCGGCCCTCGGCGCCGCGCTCGGCGGGCACCACCAGGACCAGCGTCGGGCCGCCCCCCTGCGGGTCGGCTCGGTCAAGACCAACGTGGGCCACCTGGAGGCCGCCGCCGGGATCGCGGGCCTGCTCAAGACGGCCCTGAGCATCCACCACCGGCGGCTCCCGCCGAGTCTCAACTTCGCCACCCCCAACCCCGCCATCCCGCTGGCCGAGCTCGGGCTGCGCGTCCAGACCGCGTTCGAGCCGTGGCCCGACGAGCGGCGGCGGCTCACGGCCGGGGTCAGCTCCTTCGGCATGGGCGGCACCAACTGCCATGTCGTCCTGGCCGAACCGCCCGCCGCCGCCACACCGTCGGACCGGCCCACGCCGCCCGGGGACGTGCCGAAGCGCACCGTCCCGCCGGTCACGCCGTGGGTCGTCTCCGCGGCGAGCCCGACGGCGCTCGCGGCCCAGGCCGCCGCGCTGTGCGAACACCTGCGCGCACACCCCGGACTCCACCCGGTGGACGTCGGCCACGCGCTCGCCACGACCCGGACGGCGTTCCCCCACCGAGCCGTCGTCCTGGGCACGGGGGTGGCCGAACTGCACGGCACTCTGGACGCGTTGGCGTCCGGGACACAGACGTCGGGGGTGATCCGCGGCCGCGCGGGCGGGGGCCGGGTCGCGTTCCTGTTCAGCGGCCAGGGCAGCCAGCGCCCCGGCATGGGCCGCGAGCTGTACACGGCGTACCCCGTCTTCGCCGACGCGCTGCGTGAGGTGTGCGGGCACCTGGACCCCTTGCTCGACACCGACACCCCGCTGCTGGACCTCATGTTCGCCGAGGCTCCCGCGGACGGTGAGCCGCCGCTGAACCGGACGGCGTACACCCAGCCCGCGCTGTTCGCCGTCGAGGTGGCCCTCTACCGCCTGGTGACGTCCTGGGGCCTGACCCCCGACCACCTGATGGGCCACTCGGTCGGCGAGATCACGGCCGCGCATGTGGCCGGGGTGCTGTCGCTGCCCGACGCCTGCACGCTGGTGGCGGCCCGGGGCCGCCTCATGCAGTCCATCACCACCCCCGGGGCGATGGCCGCCTGGCAGGCCACCGCCGAGGAGGCCGAGCAGGCGCTGGAGGCGCACGGCGGGCGGGTGGGCCTCGCGGCCGTCAACGCACCCGCCTCCGTGGTGATCTCCGGTGACCGCGAGGCCGTGGCGGAGGCGACCGCCGGCTGGCGGGCGCGGGGCCGCAAGGCCACCGTGCTGAAGGTCAGCCACGCCTTCCACTCCCCGCACCTGGACGGCATCCTCGGCGAGCTGCGCGCGGTCGCGGCCGGGCTGACGTTCGCCGCGCCCGCCATCCCCGTCGTCTCCAATGTGACCGGCGGGCCGGCCACCGAGGCCCAGTTGCGCTCCCCCGACTACTGGGCCGACCACGCGCGGCAGGCCGTACGGTTCGACGCCGGTGTGCGGCACCTGTGCGACGCGGGGGTCGACACCTTCCTCGAACTCGGCCCCGACGCCTCGTTGACCGGCATGGCGCGGGAGAGCGCCGCCGCATGGGCCGGGGACGCGCCTCGTCCGACGGCGGTCGCGGTGCAGCGCCGCGGCCGGCCGGAGGCGCACAGCTTCGTGTCGGCGATGGCCCAGGCACACGTACGGGGCGCGGCCGTCGACTGGGCGGCCGCCTTCGCGGGCCACGAGCCCCGGCGGGTACCCCTGCCGACGTACGCCTTCCAGCGCGAACGCCACTGGCCCGACGGGCTGGACGGGCGAGGGGCGGGGCGTACCCGGATCTCACCGGTCGCGCCGCCGGCCGAGGCGTCGCCGCGGGCCGATGCCGCGCCGCGGGCCGATGCTGCGCCGCCCGTCGATCGCGCGGCCACGGCCTCCGTGGGCGAACTGCTGGCGCTCGTCCGTACCCACGCCGCCCTCGTCCTGGGGCACGACAGCCCCGACGGCATCGACCCGGCCCTGACCTTCAAACAGCTCGGCTTCGACTCGCTGGCCGCGACGGAGCTGAGCGAACGCCTCGGCGCGGCCACGGACACCGCACTGCCCGCCACCCTCACCTTCGACCATCCGACGCCGAACGCCGTGGCGGCGTGGCTGCGCGCGGCGCACGAGGAGCAGCCGGCCACCGCCCCGACGGCGGCGGTCGGGGCGGCCACGGCCGATGACCCGGTCGCCGTGGTGGCCGTCAGCTGCCGCTACCCGGGCGGGGCCGACTCCGGCGAGGCGCTGTGGCGCCTGGTGGACGAAGGCGTGGACGCCGTGGGCGAGTTCCCCGGCGACCGGGGCTGGGATCTGGCCGAACTGTTCGGCCGGGCACCGGACGGGAGCGGCGGCAGCGCGACGGGCCGGGGCGGTTTTGTGTACGACGCGGGGGACTTCGACGCGGAGTTCTTCGGGATCAGCCCGCGTGAGGCGCTGGCCATGGATCCGCAGCAGCGCCTTCTGCTCGAACTCTCCTGGGAGTTGCTGGAACGGGCCCAGATCCCGCCGGCCTCGCTGGCCGGCAGCGCGACCGGCGTCTTCGTGGGCGCGACGGCGGCGGACTACGGGCCGAGGCTGCACGAGGCCGCCGCCGAGCTCGACGGACATCTGCTGACCGGTTCCACGCCGAGCGTGGCGTCCGGCCGGGTGGCCTACACCCTCGGCCTGGAGGGACCGGCGCTCACCGTGGACACGGCGTGTTCGTCGTCGCTGGTGGCGATGCACCTGGCCGCGCAGGCGCTGCGGCAGGGCGAATGCGATCTGGCGCTCGCGGGCGGTGTGACGGTGATGGCCACGCCGGGCATGTTCACTTCGTTCTCCCGGCAGCGCGGCCTGGCCCCGGACGGGCGGTGCAAGCCGTTCGCGGCCGCCGCCGACGGCACGGGATGGAGCGAGGGCGCCGGGCTCGTTCTGCTCGAACGCCTGTCCGACGCGCGCCGCAACGGCCACCAGGTGCTCGCCGTGATCCGCGGCTCGGCGGTCAACCAGGACGGCGCGAGCAACGGCCTGTCCGCCCCCAACGGCCCCTCCCAGCAGCGCGTCATCCGCCAGGCCCTGGCCAACGCCCGCCTCGGCCCCGCGGACGTGGACGCGGTCGAGGCCCACGGCACCGGGACGACGCTGGGCGACCCCATCGAGGCCCAGGCCCTCCTGGCCACCTACGGCGGGCACCGCCCCGACGACCGGCCACTGTGGCTGGGGTCCATCAAGTCGAACATCGGCCACACCCAGGCCGCCGCCGGTGCCGCGGGCGTCATCAAGATGGTCATGGCCCTGCGCCACGGCCGCCTCCCGGCCAGCCTCCACATCGACGCCCCCAGCCCGCACATCGACTGGTCCGGCGGCACGGTCAGGCTCCTCACCGAGCCCGTCGACTGGCCCGGGGCCGACCGGCCCCGCCGCGCCGCCGTCTCCTCCTTCGGCATCTCCGGCACC AACGCCCACCTCATCCTCGAACAAGCACCCGACCAGCCCGAACCGGAGCCCGCCACCGCCGCGGGCGGCGTGGTGCCCTGGGTGCTGTCGGCCCGTACCGCCGACGCGCTGCGTGCCCAGGCCGGGCGCCTGGCCGAGTGGGTCACCGCCAAAGCCCCGCCCTCCCCGGCGGACGTGGGGTGGTCGCTGGTCACCACGCGGTCGGCGCACCGCCACCGGGCCGTGGTCAGCGGTACGGACCGGGACGAGCTGCTGTCCGGGCTGCGCGCGGTGGCGGACGGCCCCGCGCCCGCCGCCGTCCCGGCGGGGTCCGCCCCCGGCCCGGTCATGGTGTTCCCCGGGCAGGGGTCGCAGTGGCGTGGCATGGGCGTGGAACTGCTGGACTCCTCCCCCGCCTTCGCGGCCCGCGTCGCCGCGTGCGAGGCCGCGCTCGGCGAGTTCGTCGACTGGTCCCTCACCGCCGTGCTGCGCGGCGCGCCGGGCGCGCCCGAGCCCTCCCGGGTCGATGTACTCCAGCCGTGTCTGTGGGCGGTGATGGTGTCGCTCGCCGCCGTCTGGGAGAGCTTCGGGGTGAAGCCCACCGCGGTCGTCGGACACTCACAGGGCGAGATCGCCGCCGCATGCGTCGCCGGGGGCCTCTCGCTCCGGGACGGCGCCAGGGTCGTGGCGCTGCGCTCCCGGGCCCTGCGCGCCCTCGCCGGCCACGGCACCATGGCCTCGCTCGCGCTGAGCGGCGAGGAGGCCGAGCGCTTCCTCGCGGACCTGGGCGCGGCGGCCGCGCGGGTGACGGTGGCGGTGTTCAACGGGCCGTTCTCCACGGTGGTGTCGGGGCCGACCGACCAGGTCACCGCGGTGGTGGCGGCGTGTGAGGCGGCGGGCCACCGGGCCCGCGCGATCGACGTGGACTACGCCTCGCACGGCCCGCAGGTCGACCGGCTCGCGGACACCATCCGCGCCGACTTGGCGGACCTCGCCCCCGGTGGATCGGGCGCGGTGTTCTACTCCTCCGTCACCGGCGCCCGGCAGGCGACGGAGGAGCTGGACGCCGACTACTGGTTCACCAATCTGCGCCGGCCGGTCCGGTTCGCCCCGGTGATCGACACCCTGCTGGCCGCCGGACACCGCGTGTTCATCGAGGTCAGCCCGCACCCGGTGCTGATCCCCGCGCTGCGGGAGTGCTTCGAGGCGGCCGATGTGGCGGCGGCCACCGTGCCGACGCTGCGCCGGGACCAGGGCGGCCCGGATCAAGTGGCGCGCGCCCTGGGGGACGGCTTCGCCGCGGGGCTCGCGGTCGACTGGAGCCGCTGGTTCGCGGGCGACGAGGGCGGCAGGGGCGACGAGGGCCACCGGCCGCGTACGGTCGAGCTGCCCACCTACCCGTTCCAGCGGCGGCGGTACTGGCTGGCGCCTGACCAGGGCCGCCGCGAGGGGCGTGCGGCCGGAGCCGGAACCCGGCCGGCCGGGCACGCCCTGCTGTCCTCGGCGGTCGAACTGGCCGACGGCGGCCTGGTGCTCAGCGGCCGGCTCCCCGGCGACGCGGCCTGGCTGGGCGCGCACACCGTGGCGGGCGTCCGGTTGGTGCCCGGCGCGGTCCTGGTGGACTGGGCGCTGCTGGCCGCCGACGAGGCGGGCGGGGCGTCGCTGGAGGAACTGCTGCTGCGCGCTCCGCTGGAGCTGCCCGGGGCATCCGGTGCGCCCGGAGCGCCCGGAGCGCCCGGAGGTGTGCTGGCGCAGGTCGCGGTCGGGGCCCCGGACGGGTCGGGCCGCCGTGAGCTGCGGATCTCCTCCCGGCCAGCCGAGGCCACCGCGGGCGGGGGGTGGACGTGTCACGCGGTCGGGTCGCTGGTCCCGGGCGGCCCGCCCGCTCCGGCGGACACCGGGGCGCCGGTCGCCCCCTGGCCGCCGGCGGGCGCCGAGGCGCTGGAGCCGGCCGGGCTGTACGAGCGGGCCGAGCGGCGCGGCTACGGCTACGGGCCCGCGCTGCGGGGAGTGGCGGCGCTGTGGCGGGACGGGACCGAGCTGGTCGCCGACCTGGTGCTGCCCGAGGAGGCCGGTGACGTGGGTGGCGAAGACGGCGGCGGTTCGGCCGGATTCGGTCTGCACCCGGTCCTGCTGGACGCCGCGTTGCAGCCCGCCCTGCTGACCGAGCCGGACGACGCGGGGGGCGAGGGAGAGGGGCCGGAGGCCCGGTTGTGGCTGCCGTTCGCGTGGAGCGGCGTCCGTCTGTGGGCGACCGGGGCGCGCGCCGCGCGGGTCCGGCTGACGCCGCTGGACGGGGACGGCGGGGACGATCGCGAGGTGCGGATCGAGGTGTCCGACCCGGCCGGGGCCCCCGTGCTGAGCGTGGCGTCGGTGGTGCTGCGCCCGCGCACCGTACGGCAGGTGCGCGGGGCGAGCGGGGCCGCGGCGGGTGGTCTCTTCGTCCTCGACTGGACTCCTGTGACGCCTCGGGAGCCGTCCGGCACCGAGGACGACGCCGGGTGTGTGGCCGTGCTGGGCGAGGCGCCGACGGAGCCGGGCGCGGACGGGTGCCGGGACACGTATGCGGACCTCCCGGCGCTGCTGGCCGCCCTGGACGCGGGCGTGCCCGCGCCCTCCGTGGTGGTGTGGCGGCCACCGACCGCCGACCCCGGCGCCGCGCCGGAGGACGCCGCCCTGTTCGCCGTACGGGGCGTGGCGGCGGCGCTGCGCACCTGGATCGGCGAACCGCGGCTGGCGGGCAGCCGTCTCGCGGTGGTCACTGGGTGTGCGGTCGCGGCGGGCGGCGCCGAGGGCGAGCCGGTGGACACGGCCGCGGCGGCTGCCTGGGGCTATGTGCGTGGTGTCCAGGCGGAACACCCCGGCCGCTTCGTCCTCGTCGATGTGGACACGGACACCGACATCGGCACCGACGTCGGCACGGTGGGGGCTCGGGCGGCCGCGCTCGGTGAGCCGACAGTCGCGGTGCGCGGAGACACGCTGCTCGCGCCACGCCTGGCGCGTTTCGCCGCCGCTTCGGGCGGCGTGGCGTTCGACCCGGAGGGCACGATCCTGGTCACGGACGCCGGGGGCCCGCTCGCCGGTGCGGTCGTCGAGCAGCTGGTGCGCGCGGAGGGCGTCCGCCACCTGCTGCTCGTACGGTTCGGCGGCACGGACGACACCGACGACGCGTACGGCACGCAAGACGCCCACGTACGCGTGGTCATGGTCGATCCTGGCGACACCGCCGCGCTCGAACAGGTCGTGGCGCAGGTCGATCCGGCCCATCCGCTGACCGGCGTCATCCATGTCGCGGGGCTGTCCGCCGACATCGAGACACGTGGCGCGGCGCGGGGGTGGGCCGTGGCGGCCGGGGCGGTGCGGGCGCTGCACCATGCCACCGCCGGGCTGCCGTCCGTCCGGTTCGTGACGCTCTCCGACGCCGCCACGGCCTGGGACGGCCCGGTCGCCCCCGAAAGGGCCGCGGCCGGTGCGTTCTGCGAGGCCGTGATGGACGTACGGCGCCGGGCCGGACTGCCGGGCCTCGCGGTGGCGTTCGGGCCCTGGG CCGCAGCCGATGCCGCAGCCGATGCCGACGGCGGCGACGACGACGGCGACGACGGCGGGCGCTGGACGGGGGTCCTCGGCGCGGACCGCGGGTTCGCACTGCTGCGCGCCGCCTGCCGCGCCGACGGACCGGGGCTGGTGGCGGCCGACATCCGTACCCGGGCCCTGACCGCCCACCCGGTCCATGAGCTGCCGGCCGCGCTGCGCGCGCTCGTCGCGGGGTCGGCCGGCCGGGCGCCGGTCCGGCCGGTGGCCGCCGCCGCGCCCGGCCGCGCCACCGACTGGGCGAGCCGGCTGGTGGGCCTCGGGCCGACCGAACGGCGCCGCGCCGTCCTGGAGCTGGTGCGCGATCACGCCGCCGCCGTGCTCGGGCAGCCCGACCCCAAGGCCGTACGGGCCGACGCCTCGTTCAAGGAGCTGGGCTTCGACTCGGTGACCGCCGTCGAGCTGCGCGACCGGCTGGTGGCGGCCGGCGGGCTGCGGCTGCCCGCCGCCGTCGTCTTCCGCCATCCGACGCCGGAGGCGCTGGCCCGCCGGATCGAGCAGCAGCTCGCGCCCGACGGCACGAACAACACCGACGGTGCGAACAACGCCGACGGTGCGGACAACGCCACAAAGAACGCTGGGAACAACAGCAACGGCCCGGCGCTCGACGCGGCGGACAAGCTCGCGTCGGCCACGGCCGACGAAATCCTCGACTTCATCGACAACGAGCTCGGCGTGCTCTCCGAGGCGCGTCCGCGCCCCTCCAACTGAAGGCAGGTGACGACATGGTCAGCGAGGAGAAACTGGTCGAGTACCTGCGCCGGGTCACCACCGAGCTGCACGACGCCAGGACCCGGCTGCGGGAGCTGGAGGAGGGTGAGCAGGAGCCGGTCGCGGTGGTCGGCATGGCCTGCCGTTTCCCCGGCGGGGTGCGGTCCCCCGAAGACCTGCGCCGGCTCGTCCTGTCGGGCGGCGACGCGATCGGTGACTTCCCCACCGACCGGGGCTGGGACCTGGACGGCCTCTTCCACCCGGATCCGGCGCACTTCGGCACCAGCTATGTGAGGCAGGGCGGCTTCCTGTACGACGTCGACCGGTTCGACGCGGGGTTCTTCGGCATCAGCCCGCGCGAGGCGCTGGCGATGGACCCGCAGCAGCGGCTGCTCCTGGAGCTGTCGTGGGAGGCGCTGGAGTCCGCCGGGGTGGTGCCCGGCGCGCTGCGCGCCAGCCGGACCGGTGTGTATGTGGGGGTGTCCAGCGAGGACTACATCTCCGGACTGCCGCGGATCCCGGAGGGCTTCGAGGGCTACGCCACCACCGGCAGCCTGACCAGCGTCATCTCCGGCCGCGTCGCGTACACCTTCGGCTTCGAGGGCCCCGCGGTCACCGTGGACACCGCGTGCTCGTCGTCGATGGTGGCCATCCATCTGGCGGGGCAGGCGCTGCGGCAGGGCGAGTGCTCCCTGGCGCTGGCGGGCGGCGTCACGGTGCTGTCCACGCCGCTGATGTTCACCGAGTTCTGCCGGCAGCGGGCGCTCACACCCGACGCCCGGTGCAAGCCGTTCGCCGCCGCCGCAGACGGCACCGGTTTCTCGGAGGGGGCCGGCCTGCTGCTGCTGGAGCGGCTGTCCGACGCGCAGCGCAACGGCCACGAGGTGCTGGCCGTCCTGCGGGGCTCGGCCATCAACCAGGACGGCGCGAGCAACGGGCTGACCGCGCCCAACGACGTCGCCCAGGAGAACGTGATCCGCGACGCGCTGGCGAGGGCCGGGCTGTCCGGCGCGGACGTGGACATGGTCGAGGCGCACGGGACGGGCACCCGGCTGGGCGACCCCATCGAGGCGGAGGCGCTGATCGCCACGTACGGGGCGGACCGCCCGGCGGAACGGCCGCTGTACCTCGGCTCGATCAAGTCGAACATCGGCCATACGCACGCGGCGGCCGGGGTCGCGGGCGCGATCAACACCGTGATGGCGCTGCGGGACGGCAAGCTGGCCAGGACCCTGCACATCGACGAGCCGACCCGCCACGTGGACTGGAGCTCCGGCACGGTGCGGCTGCTGACGGACCCGCACGACTGGCCGGTGACCGACCGGCCGCGCCGGGCGGCGGTGTCGTCGTTCGGCGTGTCCGGCACCAATGCCCATGTGATCCTCGAACAGGCCCCGGACCAGCCCGAACCGGCCCCGTCCGGCACCGCGGACGGCGGCCGCCACGGCGTGGTGCCCTGGCCCGTCTCGGGGCGTACCGAGGCGGCGCTGCGGGACCAGGCCGCGCGGCTGGGCGCCTTTCTGACGGCGGACGGTGCGGCGAGTGGCGCCGCGGACGTGGGCTGGTCGCTGGCGACGCGCCGCTCGGCGTTCGAGCACCGGGCCGTCGTGGTGGGCCGCGAGCGGTCGGACCTCCTCGCCGCGCTCGACGGTCTCGCGGCCGACGAGCCGGGCCCCGCGGTGGTGCGCGGGGTGGCGGCGGACGTGGGCGCGGGCCCGGTCATGGTGTTCCCCGGGCAGGGGTCGCAGTGGCTCGGCATGGGCGTGGAACTGCTGGACACCTCCCCCGTCTTCGCGGCGCGCCTCGCGGCGTGCGAACGGGCCCTGGCCGCGCATGTCGACTGGTCGCTGACCGACGTGCTGCGCGGCGCGCCGGGGGCGGCCGACATCGGCCGGGTCGATGTGGTGCAGCCGGTGTTGTGGGCGGTGATGGTGTCGCTGGCCGCGGTGTGGCAGGCGCACGGCGTACGGCCGGCCGCCGTGGTCGGCCACTCGCAGGGGGAGATCGCGGCGGCCTGTGTCGCGGGCGCGATGACGCTGGAGGACGGCGCCCGTGTGGTGGCGCTGCGGGCGCGGGCGCTGCGGGCGCTGGCCGGGCAGGGCGCCATGGCCTCGCTGGGCTGCGGTGTCGAGGGGACGGAGCGGCTGACCGCCGCACACGCGCCGGACGTGGCGGTCGCGGCGGTCAACGGCCCGTCGTCCACGGTGGTCTCCGGGCCGCCCGAGCAGGTCGAGAAGCTGGTGGCCGCCGCGCGCGCCGACGGGCTGCGGGCCCGCGCGATCGACGTGGACTACGCCTCGCACGGCCCGCAGGTGGACGGCATCGCGGACGAGCTGGCCGAGGTGCTGGCCGGGGTGTCCGGCGCCTCCTCCGACACCGCCTTCTACTCGACCGTGACCGGCGCCCGTATGGACACCTCCGGTCTCGACGCCGGCTACTGGTTCACCAATCTGCGCCGGCCGGTGCGTTTCGCCGAGGCGGTCCAGGCCCTGCTCGACGCCGACTACCGGGTGTTCATCGAGGTCAGCGCGCATCCCGTGCTGCTGCTCGGCCTGCAGGAGTGCTTCGAGGCGGCAGGCGTCCCGGCCGTGGCGATCGGCACGCTCCGCCGGGACGAGGGCGGCCCCGAGAGGCTGTGCCGGGCGCTGGCCGAGGCGCATGTCGCGGGCGTGGCGGTGGACTGGGCGAGCTGGTACGCCGAGGGGCCCGCGCCCGCGGCGGTGCCGCTTCCGGTGTACGCCTTCCAGCGGGAGCGGTACTGGCTGCCGG CCGGTGGGAGCTCCGGTCCCGGCGATGTCGCTGGCGCAGGGCTCACCGCGGTCGGACACGCGCTGCTCCCGGTGTCCGTGCGCCTGGCCGACGGGAGCCTGGTGCTCAGCGGGCGGCTGCCGGAGGCGGCGCGGGGCGGCTGGCTGGCCGAACACCTGGTCGCGGACCTGCCGTTGCTGCCCGGCGCGGTGCTGGTCGAATGGGTGCTGCGGGCGGCCGACGAGGCCGGCTGCGGCGGTGTCGAGGAGCTGGCGCTCCAGGTCCCGGTGGCGCTTCCCGCATCGGGCGGGCTGGTGATCCAGGTGGTCGTGGACGCCGCCGAGGGCGACGGGCGCCGTCCGGTGCGGGTCTACTCCCGGCCCGAGGAGGACACAGCGGCGCCGGACACCTGGGTCTGCCATGTCTCGGGCACGCTGCTCCCCGGCGCGGCCGGGCCGGTTCCGCCGCCCGGTCTCGGCGGGGCGTGGCCGCCGCCGGGGGCGCGGCCGGCGGCGATCGAGGGGTTCTACGAGCGGGCCGGGGCAGCTGGTTACGGCTACGGCGCGTTCTTCCGGGGCCTCGCCCACGTATGGCACGACGGCGAGGACACGCTGGCGGAGGTGGTGCTGCCCGAGGAGGCGGCGGAGCAGGCGGGTGGCTTCGGTATCCATCCCGCCCTGCTCGACGCGGCGATGCAGCCCGTACTGCTGGCCGGTCAGCTCGCCGCCGCGCCGGGTGTCGACGCGGCGCCCGGGACGGGGACGGTGCTGCTCCCGTTCACCTGGAGCGGGGTGCGGCTGTGGGCGGGTGGCGCCACCCGGCTCAGGGTCCGGCTGTCGCCGCGGCCGGAGGGGCTGCGGGTGCTGCTGGCCGACGCCACGGGCGCCCCCGTGCTGACGGCGGACGCGGTCGCGCTCCGTGAGACGGGCGTCCGGCAGTTGCGCGCGTCGAGCCGGGTGCGGGGGTCGCACGGGCTGTTCGCCGTCGAATGGATGCCGCCGCTGTCCGCCCCGGCGGGCGGGACGGCGTCCGGGACGGCCCCCGCGTCGCTCGCGGTGCTGGGCGACGAGGCCCCGGACCTGGCCGGCGCCGACCGTTATCCCGACCTCGACGCGCTGTTCCGCGCCGTGGACGGCGGAGCCACCGCACCGGATGTCGTCGTCGCCCCGGTGCGTACGGACCCGGCGGAGGCGGACACCGGCTTGGCGGCCGCGCGGCGGACGCTGGCGCTGGCCCAGGAGTGGCTGGCCGGCAGCGGGGTCGAGGGGGCGCGGCTCGCCGTGGTCACCCGGTCGGCGGTGCGGACCGGGGACGGCGACCCGGAGCGGGTGGACCCCGCGGCGGCCGCGGTGTGGGGGCTGGTGCGCAGCGCCCAGACGGAACACCCGGGGCGTTTCCTCCTGATCGACATCGACACCGACACCGACACCGACGCCGACGCCGACACCGGCCTGGAGGCATTGCGGGACGCGTTGCGGGAGGCGGTGCGTACGGACGAGCCGCAGCTCGCGCTGCGTGGCGGGCGCGCGTTGGTGCCCCGGATGGCCCGGGTGGACGCCGAGCGGGAGCTGGTGGCCCCGGCGGGTGAGCGGGCGTGGCGCGTGGTGGCCGGCAAGACCGGCCCCGACGACCTCACGGCGGTGCCCAGCCCCCGGGCCTCGGCTCCCCTCGCGCCCGGCCAGGTGCGTATCGCCGTACGGGCCGCGGGGCTCAACTTCCGCGATGCGCTGATCGCCCTGGACATGTACCCGGACGCGGCGGCGTCGATCGGCAGCGAGGGCGCCGGTGTCGTGCTGGAGGTGTCCGAGGGGGTGGCCGGGATCGCCGTCGGCGACCGCGTGATGGGCCTGTTCGACGACGCGTTCGGCCCGGTGGCGGTGGCGGACGCCCGGATGGTCGCCCCGGTGCCGGACGGCTGGAGTTTCCGGGAGGCCGCGGCGGCCCCGGTGGCGTTCCTGACCGCGTGGTACGGCCTGGTGGAGCTGGGCGGGCTGCGCTCCGGCGAGACCGTGGTGGTCCACGGTGCGGCCGGCGGCGTGGGCATGGCCGCCGTCCAGGTCGCCCGGCACCTGGGCGCGGAGGTGTTCGCGACGGCGAGCCCGGCGAAGCACCCGGTGCTGGAGGGCATGGGTGTGGACGCCGCCCACCGGGCGTCCTCGCGGGATCTGGGCTTCGAGGCGGCGTTCTCGTCGGCGACCGGCGGCCGGGGCGTCGACGTCGTCCTCAACAGCCTGGCCGGGGAGTTCACGGACGCCTCGCTGAGGCTTCTCGCACCCGGCGGGCGGCTGATCGAGATGGGCAAGACGGACGTACGCGACCCCGATCAGGTCGCCCACGAACACTCGGTCGCCTACCGGGCGTTCGACCTGATCGCGGACGCCGGTCCGGAGCGCATCGGGCGGCTGCTGGCGGCCCTGGGCGAGCGGTTCGCCGACGGCGCGTTCACGCCCCTGCCCGTCACCGGGTGGCGCCTCGGCCAGGCCAGGCAGGCGCTGCGGCGGCTCAGCCAGGCCCGGCACACCGGGAAACTGGTGCTTGACGTGGATCCGGCGCCGGACCCGGACGGCACGGTGCTGATCACGGGCGGCACCGGCACCCTCGGCGGCCTGATCGCCGAACACCTGGTGCGCTCGCACGGGGTACGGCATCTGCTGCTGCTCAGCCGGCGCGGCCTGAGCGCCCCGGGCGCCGAGGAGCTGACGGCCCGCCTCACCGAACTGGGCGCGCGGGTGCGGGTGGCCGCGGTGGACGTCGGGGACGCCACCGCCCTGGACGAGGCGGTCGCGGGCGTCGACCCGGCGCATCCGCTCACGGGCGTCGTCCACGCCGCGGGCGTGGTGGCCGACGCGATGCTGCCCTCGCAGGACGAGGAGCGCCTGGCGGAGGTCTGGTCGGCCAAGGCCGCGGCGGCGGACCGTCTGCACCGCGCGACCGCCGGGCTGCCGCTGGCCATGTTCGTGCTGTTCTCGTCGTTCGCGTCCACCCTGGGCACCCCGGGGCAGGCCAACTACGCGGCCGCCAACGCGTACTGCGACGCCCTGGTCGAGCGGCGGCACGCCGAGGGGCTGCCGGGCGTGTCGGTGAGCTGGGGTCTGTGGTCCGCCGCGAGCGGGCTCACCGGAGGGCTGACCGAGGCCGATGTGGCGCGCATCGCCCGGCAGGGCATCGTCCCGAACAGCACCGAACAGGGACAGGACCTGTTCGACGCGGCGCTCGGGCACGGGCGGCCGGCGCTGCTCGCGTGGAACCTGGACACCCGGGCGCTGGCCGCGCAGCCCGTCGCGGCCCTGCCCGCGCCGCTGCGCGCCCTGGCGGCGGACGCCCAGGCGGGCGCCCGCCTGGCCGGCCCGGCGGCGCGGCCGACCGCGGCGGCGGCCGAGGAGCCCGGGGACTGGGCGGCCCGGCTGGGCGCCCTCGCCCCGGCCGAACAGCGGCGCCTGCTCACCGACCTGGTGCGCAGGCACGCCGCCACCGTGCTCGGCCACGCCGACCCCGAGGCCGTACCGGCCGACGCGGCGTTCAAGGAGCTCGGGTTCGACTCGCT GACCGCCGTCGAGCTGCGCAACCGCGTCACCGCCGCCACCGGGCTGCGGCTGCCCGCCACGGTCATCTTCGACTACCCGGAGCCGGGGGCGCTGGCCGAGCACCTGCGCGCCCAACTCGCCCCCGAGGCGGGGGCGACGACGGCGCCGGACCTCTACGCGCCCGTACTCAGCCGGCTGACGGGCCTGGAGGAGACCCTGACGGCCCTCACCGCGTCCGGGGTGAACGGCGGTACGAGCACAGCGGCCGACCCCGGCGCGGTGACGGCGCGTCTGGAGTCGCTGCTGGCCACGTGGAAGGCGGCGCACGCCCCGCACCGGAACGGCGGCACCGCGGCCGAACGGCTCGAAGCCGCGACGACCGACCAGGTCCTGGACTTCATCGACAAGGAACTCGGAGTGCAATGAGCCCGGTCTGCCAGGAACGCCGAGAATCCCGAGAAACCTCGAAGGCGAAGTGACGCGCCGTGACCACTGAGACCAACGAAGAGCGGCTGGTCGACTATCTCAAGCGGGTCGCCGCCGATCTGCACGACACCCGGGCGCGGCTGCGCGAGGTGGAGGACGGGCAGCGGGAGCCGGTGGCCATCGTGGCGATGGCCTGCCGCTACCCCGGCGACGTCGCCTCCCCCGAGGCCCTGTGGGACCTCGTCGCCGCGCGCCGGCACGCGATGACCGCGTTTCCGGACAACCGCGGCTGGGACCTGGAGCGGCTGTTCCACCCGGACCCCGACCACCCGGGCACCAGCTACGCCCGCGAGGGCGGATTCCTGCACGACGCCGACCGGTTCGACCCGGAGTTCTTCGGCATCAGCCCCCGCGAGGCGGCGGCGGTCGACCCGCAGCAGCGGCTGCTGCTCGAAGTGGCCTGGGAGGCGCTGGAGCGGGCGGGCATCGCGCCCGGGTCGCTCAAGGGCGCGCCCGTCGGCGTGTACGCGGGCACCGCCCTGCCCGGCTTCGGCACCCCGCACATCGACCGGGCCGCGGAGGGTTATCTGGTCACCGGCAACGCGCCGAGCGTGCTGTCCGGCCGGGTGGCGTACACCCTGGGTCTTGAGGGGCCCGCGGTCACGGTGGACACGGCGTGTTCGTCGTCGCTGGTGGCCATGCACCTGGCCGCTCAGGCGCTGCGGCAGGGCGAGTGCGAGCTGGCGCTGGCGGGCGGCGTGACGGTCATGACCACGCCTTACGTGTTCACGGAGTTCGCGCGGCAGCGCGGCCTGGCGGCCGACAGCCGGTGCAAGGCCTTCTCCGAGGCGGCCGACGGCACGGCCTTCGCCGAGGGTGCGGGGCTGCTGGTGCTGGAGCGGCTGTCGGACGCCCAGCGCAACGGGCACCCGGTGCTGGCCGTGGTGCGCGGTTCGGCGATCAACCAGGACGGCGCGAGCAACGGGCTGACCGCGCCCAACGGCCTGTCGCAGCAGCGCGTCATCCGGCAGGCGCTGGCAAGCGCCCGGCTCTCCCCGGCGGATGTGGACGCCGTCGAGGCACACGGCACGGGCACCACGCTCGGCGACCCGATCGAGGCCCAGGCGCTGCTGGCCACCTACGGTCAGGAGCGGCCCGAGGGGCGGCCGCTGTGGCTGGGCGCGATCAAGCCGAACCTCGGGCACACGCAGGGCGCGGCGGGCGTCGCCGGCGTGATCAAGATGGTGATGGCGCTGCGGAACGCCTCGCTGCCCGCCCTGCTGCACGCCGACCGGCCCACGCCCGTGGTCGACTGGGACGGCGGCGCGGTGCGGTTGCTGGCCGAGCCGGTCTCGTGGCCGGCCGGGGACCGGCGGCGCCGGGCCGGTGTCTCGTCCTTCGGCATCAGCGGCACCAACGCGCATCTGATCCTGGAGGAGGCCCCGCCACGGCCGGACACCGAGCTGCCCGAGAACGGGCCTCAGCGGCCGGAGGGCACCGCCGTGCCGTGGGTGGTGTCCGCGCGCGGCGCGGCGTCGCTGCGGACGCAGGCCGCGGCGCTCGCCGAGCACGTGGCGGCGCACCCGGACGTCCCGGCCCGCGACATCGGCTGGTCGCTGGCCACCACGCGCTCGCCGCTCGACCACCGCGCGGTCGTGCTGGGCGCGGACCGCGAGGAGTTGTCGGCCCGGCTCGCCGACCTCGCCGAAGGGCGGACACACCCCGATGTGACGCGGGCGTCCGCTCCGGCGCGGCTCGGTGGCAGCGCGTTCCTCTTCACCGGGCAGGGCAGCCAGCGCCCGGGCATGGGCGCCCAGCTGTACCGGGCCCACCCGGTGTTCGCCGCCGCGTTCGACGAGGCGTGTGCGGCCCTGGACCCCCAGCTTGACCCCCATCTGGGGCGGTCGCTGCGGGAGTTGGTGTTCGCACCGGCCGACGGAGACGGGGCCGGGGCGGGCGCGCTGGACGCGACGGAGGTGACCCAGGCCGCGCTGTTCGCGGTCGAGGTCGCCCTGTACCGGCTGGTCGAGTCGTTCGGTGTGGTCCCCGGCTATCTGGCGGGACACTCGGTCGGCGAACTGGTCGCCGCGCATGTCGCCGGGGTGCTGTCGCTGCCGGACGCGGCGCGGCTGGTGGCTGCCCGGGGGCGGCTGATGCAGGCGCTGCCCGAGGGCGGCGCGATGGTCGCGCTGGAGGCCGCCGAGGAGGAGGTGGCGCCGCTGCTCGCCGGACGGGCGGACCGGGTGGCGCTGGCGGCCGTCAACGCGCCGACGTCGGTGGTGGTCTCGGGCGACGAGGAGGTGGTCGAGGAGATCGCCCGTACGATCCGGGAGCGGGGACAGCGCACCAGGCGGCTGCGGGTCGGCCACGCCTTCCACTCGCCGCGGATCGACCCGATGCTGGAGGAGTTCCGGCGGGTCGCCGCCTCGCTCACGTACGCCCAGCCGCGGATCGCCGTCGTCTCGAACGTCACCGGCGCCCTGGCCGGGGCCGAGCAGCTGTGCGACCCGGACTACTGGGTGCGGCACGCGCGGCAGCCGGTGCGGTTCCGCGACGGCGTCGCCGCGCTGCGCGCGGAGGGCGTCACCCGCTTCCTGGAGCTGGGCCCGGACGCCGTGCTCACCACCATGGCGCGTGACTGCCTGACCGCGGAGGGGGCCCCCGGGGCAGCCGCCGGGGAATCGGCTCAGGGTGCGGGTCCGGGGTCCGGTCCCGGCGCGCCGGTGTTCGCCACGGTGCTGCGCAAGGGCCGCGACGACTCCCGTACGCTGCTGACCGCGCTCGCCCGGCTCCATGTGGACGGCGAGAGCGTCGACTTCTCCGCCGCCTTCCCGCCCGGCGCCCGCGCCACCGACCTGCCCACCTACCGCTTCGACCGGCGCCGCTACTGGCGCGACGCCCCGCAGGCGGAGGCGGACGTACGGGCCGCGGGGCTCGAGGCGAGCGACCACCCGCTGCTGGGCGCAGCCCTCGAACCGGCGGACGGCGGGCTGCTGCTGACCGGCCGGCTGTCGCTGCGGAGCCAGCCCTGGCTGGCCGACCACGCCATCGTGGACGCCGTGCCACTGCCCGGCACGCTCTTCGTGGAGCTGGCCCTCCAGGCCGGCGAGCGGA CCGGCTGCGACCGGATCGACGATCTCACCCTGGAGGCGCCGCTGCTGCTGCCTCCGGTGGGTGCGGTGGACCTCCAGGTGGCCGTCGGGGCCGCCGACGCGGCCGGCCGCCGGGCCGTCACCGTCTATTCGCGCCCGTCCGGCGACGGCTCGGCGGACCCTGGTGTCCCGGAGGAGTCGGGCGACGGCCCGTACAGCCCGTGGCGCCGGCATGCCACCGCCACGCTCGGCACCGCGCCGGCCGGCGCGGGGACCGGCGTCACCGAGCCCGCGGCGGAGCCGGCCCAGTGGCCGCCCGCCGGGGCGGAGGCCATCGACGTGGCCGGGCTGTACGAGCGGCTGGCCGCCGAGGGCTACCGGTACGGGCCCGCGTTCACCGGGCTGCGCGCCGCGTGGCGGGTCGGCGAGGAGATGTTCGCCGAGGTGAGCCTCGCCCCGGACCGGCGGGGCGACGGCGCGGCGTACGCCGTCCACCCCGCGCTCCTGGACGCCGCGCTGCATCCGATCGGCGCGCTGTTCACCGGCGAGGACCAGGCGGGCGGCGCACCGGGCACGGTCCGGCTGCCGTTCTCCTTCGGCGGCGTACGGCTGCTCGCGCGCGGCGCGTCCAGGCTGCGGGTCCGTATCACGCCGACCGGGCCGGACACCGTGACCATGCGGCTGTCCGACGACGCCGGTGCCGAGGTCGTGGCCGTCGACTCGCTCACGCTGCGCGCCGTTTCCGCGCGGCGGTGGCGGTCCGGCGCGATCCCGGCGGACAGGCCGCTGTACCGGCTGGACTGGGAGGCCTTCGCGCCGCCCACCCCCGCGGTACCGGCGCCGGACCGCTGGGCCGTGGTCGCCACGGACGCCGTGAACGGGCCCGACAGCGCTGGCCGTACGGGCGGGACGTTCGCCACCGACGCCGCCACGGCCTCGCTGCCCGGGGAGCACGTCACGCGCCACCCGGACCTGGCCGCGCTGAGCGCGTCGGTCGCCGCCGGCGCCCCGGCCCCCGACCTGGCCGTCCTGGCCTGCCTCGGCGCCCCGTACGACACGTCGGGCGGCGACGAACCGCCCTCCCGGGTACGCGCCGCCACCCGCCACGTCCTCGCGCGGCTGCGGGAGTGGCTGGCGGACGACGCCCTCGGCGCCTGCCGGCTGGTGGTCCTCACCGCCGGAGCCGTGGCCGCCGGCCCGGACGACGCGCCGGCCGACCTGGCGGGCGCGGCGGTCCTGGGCCTGCTGCGCGCCGCCCAGGCCGAACACCCGGGGCGGCTCGTGCTGGTGGACACCGACGACGCCCCGGCGTCCCGGGACGCGCTGGCGGCGGCGGTGGCCGCCGCCGTGGCCGCCGGCGAGGGGCAGCTGGCGCTGCGCGAGGGGCGCGCGCTGGTGCCCCGGCTGGTGCCGGCGCACCCCGACCCCGACGCGGAGCCGGCGGCGCTCGACCCCGACGGCACCGTGCTGGTGACCGGCGGCACCGGCTCGCTCGGCCGGCTGCTCGCCCGCCACCTCGTCGAGGCGCATGGCGCCCGGCATCTGCTGCTGGTGAGCCGGCGCGGGCCGGCCGCCGAGGGCATCGAGGCGTTCGCGGCCGGGCTCGCGGCCGACGTACGGATCGTCAGCTGCGACACCTCCGACCCCGAGGCGCTGGCCGCCCTGCTCGCCACCGTCCCCGAGGAGCACCCGCTGACCGCGGTCGTGCACACCGCGGGCGTACTCGACGACGGCGTGGTCACCTCGCTGACGCCCGAACAGCTCGACGCCGTGCTGGCGCCGAAGGTGGACGCGGCCTGGCATCTGCACCGGCTGACCCGGGGCGCGGACCTCGCCTCCTTCGTCCTGTTCTCGTCCGCCGCCTCCGTGCTGGGCAGCGGCGGACAGGGCAACTACGGCGCGGCGAACGCGTTCCTCAACGCCCTCGCCGAGCACATCCGCGCCGCGGGCGGCCCGGCCACCTCACTGGCCTGGGGCCTGTGGGCGGTGGACGAGGGGATGACGGAACACCTCGCCACCGCGGATCTGGCCCGGATGGCGCGCTCGGGCACGGCCGCGATGTCCGGGGATGCGGGCCTGGCCCGGTTCGACGCGGCGCTCACCTCCGCGCCGCCCGTGCTGATCCCGGCCAGGTTCGACCTCGCCGTCCTGCGCGAGCAGGCGGCCGCGGGCACGCTGCCCCCGCTGCTGCGCCGCCTGGTGCGCCTGCCCGTCCGTACGGCCGCGGCTACCGAGGCGTCACCCTCCTGGGCCGGGCGGCTCGCCGGGCTGCCGGAGAGCGAACAGGACCGGGTGATCGGGGAGCTGATACGCGACCGGATCGCCGCCGTCCTGGCGCACCCCGACCCGGAAACCCTCGAACTGGGCCGGACGTTCTCGCAGCTCGGTCTCGACTCGCTGACCGCGCTGGAGCTGCGCAACGCGATCCATGAGGCCACGGGTGTCCGCCTCCCGGCCACGGCCGTCTTCGACTACCCGACCCCCGAGACCCTGGTGAGCCATCTGCGCACCGAACTGCTCGGCGCCACCGCGGCCACCGCGCCGCTGCCGCCGGGGGCCGGAGCGCCGGCCCGGTCGGAGAGCGCGGAGGACCCCGTCGTGATCGTCGGCATGGCCTGCCACTACCCGGGCGATGTGCACTCCCCGGACGAGCTGTGGCGGCTGGTGGCCGACGGGGTGGACGCGATCGGGCCGTTCCCCGAGGACCGCGGCTGGGACGTGGCCGGGCTGTACGACCCCGACCCCGAGCGCACCGGCAAGAGCTACGCCAGGGAGGGCGGCTTCCTGCACCAGGCGGCCCTGTTCGACGCGGAGTTCTTCGGGATCAGCCCCCGGGAGGCGCTGGCCACCGACCCGCAGCAGCGGCTGCTGCTGGAGACGGCGTGGCAGGCGTTCGAGCACGCCCGGATCGATCCGGCGGCGCTGCGCGGCAGCCGGACGGCGGTGGTCACCGGCATCATGTACGACGACTACGGCGCGCGGTTCCTCGGCCGGATCCCGGAGGGGTACGAGGGCCAGATCATGACCGGTTCCACGCCGAGCGTGGCGTCCGGCCGGGTGGCCTACACCTTCGGCCTGGAGGGGCCGACGCTGACCGTGGACACGGCGTGTTCGTCGTCGCTGGTGGCGATGCACCTGGCCGCGCAGGCGCTGCGGCAGGGCGAATGCGAGCTGGCGCTCGCGGGCGGTGTGACGGTGATGGCCACGCCGAACACGTTCGTCGAGTTCTCCCGCCAGCGCGGCCTGGCGCCGGACGGGCGGTGCAAGCCGTTCGCGGCCGCCGCCGACGGCACGGGATGGAGCGAGGGCGCCGGGCTGCTGGTGCTCGAGCGGCTGTCGGACGCGCGCCGCAACGGGCACCGGGTGCTCGCGATCCTGCGGGGTTCGGCGGTCAACCAGGACGGCGCGAGCAACGGCCTGACCGCGCCCAACGGCCCCTCCCAGCAGCGGGTGATCGGCCAGGCCCTGGCCGCGGCGGGGGTGGATCCCGCCGGGGTCGATGTGGTGGAGGCGCACGGCACGGGTACGACGCTGGGCGACCCCATCGAGG CCCAGGCCCTGCTGGCCGCCTACGGCCGGCACCGCCCGGACGACCGGCCGCTGTGGCTGGGCTCTGTGAAATCGAACATCGGGCACACCCAGGCCGCCGCCGGTGCGGCGGGCGTCATCAAGATGGTCATGGCCCTGCGCCACGGCCGGCTGCCCGCCACCTTGCACGTCGACGAGCCCAGCCCGCACGTGGACTGGGCGGGCGGAAACGTCCGGCTGCTCACCGAGGCCACCGACTGGCCCGAGACCGGCCGGCCCCGCCGCGCCGCGGTCTCCTCCTTCGGTATCTCCGGCACCAACGCCCATCTCATCCTGGAACAGGCGCCCGACCAGCCCGGACAACCACGGCCGGAGCAGCCGGAGTCCGCCGCCGCGGGCGGCATCGTGCCCTTCGTGCTCTCCGCCCGCACCGCCGAGGCGCTGCGCGCACAGGCCGCGAACCTGGCGGGGTGGCTCCCCTCGGCCGAGGTGGCGGAGGTGGGCTGGTCGCTGGCGACCACCCGCTCGGCCTTCGAGCACCGGGCGGTGGTCGTGGGCGAGGACCGGGACGCGCTGCTGGCCGGTCTGGAGAAGCTGGCCGCGGACGAGCCCGATCCGGCGGTGGTGGCGGGAGCGGCGACCGCCGCGGCCGCGGGCCCGGTGTTCGTCTTCCCGGGCCAGGGGTCGCAGTGGCGCGGCATGGGCGTGGAACTGCTGGACACCTCGCCGGTGTTCGCGGCCCGGATCGCGGAGTGCGAGCGGGCCCTGGCGCCGTACGTGGACTGGTCGCTCACCGCCGTACTGCGCTCCACCGAGGCCGACACCGGCACCGGTACCGGCACCGGCACCGAAGCCGCCGACCTCCAGCGCGTCGATGTCGTGCAGCCCACCCTCTGGGCGGTGATGGTGTCCCTGGCCGCCCTGTGGCAGCACCAGGGCATCACCCCGGCCGCCGTGATCGGCCACTCCCAGGGCGAGATCGCCGCCGCCTGTGTGGCCGGGGCCCTCACCCTCGACGACGCCGCCAAGGTGGTGGCCCTGCGCAGCCAGGCGCTGCGCGCCCTGGCCGGCCACGGCACCATGGCCTCGCTGACCCTCGGCGCCGACGACACCGCCCAGCTCCTGGACGAGCTGGGCGACCAGGCCGACGACGTCACCCTGGCCGCCGCCAACGGGCCCGCCACCACCGTCGTCTCCGGCGCGGTGGAGCAGATCGCCACCGTCCTGGCGGCCGCCGAGGCGCGCGGCGCGCGGACCCGCACCATCGATGTGGACTACGCCTCGCACGGGCCCCACGTCGACCGCATCCGCGAGGACATCGTCTCCGTCCTGGGCGACCTCGCGCCCACCGCCTCCGACATCGCCTTCTACTCCACGGTGACCGCCGAACGCCTGGACACCGCAGGGCTCGACGCCGACTACTGGTTCACCAACCTCCGCCGGCCGGTCCGCTTCGCCGACACCCTCACCGCCCTCCTCGCCCATGGACACCGCCACTTCATCGAGGTCAGCCCGCATCCCGTGCTGATCCCCGGGATGCAGGACGGCTTCGAGGCGGCCGGCGCCCCCGCCACCGCCGTCCCCACCCTCCGCCGCGACCAGGGCGGGCCCCACCAGCTCGCCCAGGCCGTGGCCCGCGCGTACACCACCGGTCTGGCCATCGACTGGGCGCCGTGGTACCCGGCCGGGCCGCGCACCACCGATCTGCCCACCTACCCCTTCCAGCGCCGCCGCTACTGGCTCGGCATGGACGGCGGACCGGGCGATCTGCGCGGCGCCGGACTCACCTCGCTGGCCCACGCCCAGCTCGGCGCCGCGGTCGAACTGGCCGACGGGGGGCTGGTGATGACCGGCCGGCTGCCCGCCGCCGGGAACGGCGGCTGGCTCGCCGACCACGTCGTCGCCGACACCCCCCTGGTGCCGGGCACGGCCCTGGTGGAGTGGGTGCTGCGGGCGGCCGACGAGGCGGGGTGCGGCGGGATCGAGGAGCTGGCGCTCCATGTTCCGATGGCGCTGCCCGCGTCCGGTGGGCTGCGGGTCCAGGTCGTGGCGTACGCGCCCGACGGGGACGGCCGCCGCGAGGTGCGGGTGCACTCCCGCCCCGAAACGGAGGACGGCTCGTCGCCCTGGACCTGCCACGCGACCGGACACCTCTCCCCGACCGCCCCGGGCGCCGCGGACCCGGCGCCGGCGGGGGTGTGGCCGCCGCGGGACGCCGAGCCGCTGGACGTGGCCGGCTTCTACGGCCGCGCCGAGGCGATCGGCTACGGCTACGGCCCGGCCTTCCGGGGCCTGACCGCCGCCTGGCGGCAGGGCGCCGACCTGCTCGCCGAGGTGGTGCTGCCGGAGGCGGCCCACGAGGGGGCCGACGGGTTCTCCCTGCACCCCGCGCTGCTCGACGCGGCCCTGCACCCTCTGGCCCTGGACGGCCGGGGTGAGGACGGGCGGATGCGGCTGCCGTTCGCGTGGAGCGGTGTGTCGCTGTGGGCCACCGGGGCACGCGCGGCCCGGGTCCGGATGTCCCCGCTGGAGCACGGCTTCCGGCTGGTGGTGGCCGATACGGCGGGCCAGCCGGTGCTCAGCGCCGAGTCCGTGGTCGTACGCCCGACGAGCGCGCGGCAGTTGCGCGAGGCGGGCGCGCGGCGGGTGGACGGGCTGTACGCGGTGGCGTGGGTGCCCCTGCCGACACCGTCGGACACCACGGCGCAGGTGGAGGCGGGGGCCGCCGAGGGGTGGGCGCTGCTGGACGGCGGCCCGCTCCCGTTCGACCCGTCAGAGGCCGGATCGCCGCCCCGTCACGCCGACATCGACGCCCTGCTCGCCGCCCCCGCCAGGCCTCACACGGTGCTCGTCGGCGTTCCGGCCGCCGAGGGCGACCGGGAATCGGCCGACGGCGCGTTGGCCGTGACCACCGGTGTGCTGACGCTGGCGCGTCGGTGGCTGGACACGCCGGAGCCGGCCGACGCCCGGCTGGTGCTGGTCACCCGGGGCGCGGTGGCGGCTGCGGAAACCGACAACGGCCCCGACCCGGCGGCGGCCGCCGTGTGGGGGCTGCTGCGCAGCGCACAGGCGGAGAACCCGGGCCGTTTCCTGCTGTGCGACATCGACGACGGCGCCGGGCCCGACGATGTGCTCGGCGCCGTCACCCGGGCGGTGGCCCTGGACGAGCCACAGGTGGCGGTGCGCGGTGGCCGCGTGCTGGCGCCCCGGCTGGAGCGGGCGGGCGCACCGGAGCTGATGCCGCCGCCGGACGAACCGGCATGGCGGCTGGCGGCCGGTGACACCGGCACCATCGACAGCGTTTCGGTCGTGGCCTGCCCGGAGGTGCTGGAGCCGCTGGCGCCCGGCCAGGTGCGGATCGGGGTGCGGGCCGCGGGCATCAACTTCCGCGATGTGCTGATCGTGCTCGGGATGTATCCGGACGAGGGGGTGTTCCGGGGCAGCGAGGGCGCGGGTGTGGTGCTGGAGGTGGCCGGGGACGTGACGTCGGTGGCCGTCGGCGACCACGTCTTCGGGCTGTTCGAGGGCGCCTTCGGGCCCGTGGCCGTCGCC GACGCGCGCGCGGTCGTGCCCATCCCGCCGGGCTGGACGGACCAGCAGGCCGCGGCCGTCCCGACGACGTTCCTGACCGCCTGGTACGGGCTGGTGGACCTCGCGGGCCTCAGGGCGGGCGAGTCGGTGCTCATCCATGCCGCCACGGGCGGCGTGGGCACGGCGGCCGTGCAGATCGCCCGCCACCTGGGCGCCGAGGTGTACGCGACGGCCAGCCCCGGCAAACACGCCGTACTGGAGGCCATGGGCATCGACGAGGCCCACCGCGCCTCCTCCCGCGACCTCGACTTCGAGGAAGCCTTCCGCACCGCCACCGGCGGCCGCGGCGTCGACGTGGTCCTCAACAGCCTCGCCGGCGAGTACACCGACGCGTCCTTGCGCCTGCTGTCCGAAGGTGGGCGCTTCGTCGAAATGGGCAAGACCGACAAGCGCGACGCCGAGCAGATCGCCGAGGCGTACCCCGGTGTCCGCTACCGCTTCTACGACCTGGTGCCGGACGCCGGTTTGGACCGGGTCGCGGAGATGCTGGACACGCTCGCCGGCCACTTCGCGCGGGGCGTCCTGGCGCCGCCGCCGGTGCGGGCGTGGCCGCTGGCCGAGGCCCGCCAGGCGCTGCGCCACATGAGCCAGGCCAAGCACACCGGCAAATACGTGCTGGACATTCCCCGCACGCTCGACCCCGACGGCACCGTCCTGATCACCGGCGGCACCGGCACCCTCGGCGCCCTGGTCGCCGAACACCTCGTCACCACCCACCACATCACCCACCTCCACCTGCTCAGCCGCCGGGGCCCGGACGCTCCCGGCGCCGCCGATCTGACGGCCCGGCTCACCGAGCTGGGCGCCACCGTCCGTATCACCGCCACCGACACCACCGACCCCCAGGCCCTGCGCCAGGCCCTCGACACCGTCGAGCCCGACCACCCGCTCACCGGTGTCATTCATGCCGCGGGGGCCCTGGACGACGCGGTGCTGACCGCGCAGACCCCGGAGCGGCTGGCGTCGGTCTGGGCGGCGAAGGCGACGGCCGCGGCCAATCTCCACCGGGCCACCCAGGGGCTCCCCCTGGCCATGTTCGTGATCTTCTCCTCGGCCGCCGGCACCCTCGGCACCCCGGGGCAGGCCAACTACGCCGCCGCCAACGCCTACTGCGACGCCCTCGCCACCCGGCGACACCGCGCGGGACTGCCCGCCACCTCCATCGCCTGGGGACTGTGGGCCGCCACCAGCGAGATGACCGGCCATCTGGCGGAGGGCGACCTGGCCCGGATGAGCCGCACCGGCTTCACCCCGCTGTCCACCCCCAAGGCGCTGGCGCTGTTCGACGCCGCCCGGCGCCAGGGCGGCGCGACCCCGCTGGCGCTCGACCTCGATCCGCGGACGCTCGGCGCCCAGCCGTCCGACGCGGTGCCCGCCGTGCTGCGTACCGTCGCCGCCGCGGGAGCACCGGTCAGGCGTACCGCAGCCGTCGCAGGGTCCACCGACTGGGCCGGCCGCCTGGCCGCGCTCTCCGACGCCGAGCGCCACCGCGAGCTGGTCAACCTGGTGCGGACGCACGCGGCGACGGTGCTCGGCCACAGCGACCCCGCGGCGCTCCGCGCGGACACCTCCTTCAAGGAGCTGGGGTTCGACTCGCTGACCGCGGTGGAGCTGCGCAACCGGCTCTCGGCCGCGACCGGGCTGCGGCTGCCCGCCGCGCTCGTCTTCGACTATCCCGACGCGGAGACCATGGCCCGCTTCCTGGACCAGAAGCTCGCCCCCGCGGACCGGACGGATGCGGCCGTCGACCGACTCGCGCCCGTCCTGAACGACTTGGCCCGGCTGGAGTCCACTTTGGGCAGCCACGACGTGGACGGGAAGGCGCGCGAGACGATCGCGGGCCGGCTCCACGCCCTGCTGTCCAGGCTGGAGGGGTCCACGGCCAGTGCGGCGGACATCGACGGCGAGGCGCTGGAGTCCGCCTCGGACGACGAGATGTTCGCGCTCATCGACCAGCAACTGGGCTCGTCCTGACGAGAGGTGGGGGAGGACCAATGCCGTCCACGGAAGACAAGCTGCGCCAGTACCTCAAGCGGGTCACCGTCGACCTGGGCGAGGCCCGGCAGCGCCTGCGCAAAGCGGAGCAACGCCACCACGAGCCCATCGCCATCACCTCCATGGCCTGCCGCTACCCCGGCGGCGTCACCTCCCCGGAAGCCCTGTGGGAGCTGGTCGACAGCCGGACCGACGCCATCGGCCCCTTCCCGGCCAACCGCGGCTGGAACCTGGCCGCCCTCTACCACCCCGACCCCGACCACCCCGGCACCAGCTATGTCCGGGAAGGCGGCTTCGTCCACGACGCCGACGAATTCGACGCCTCCTTCTTCAACATCTCCCCGCGCGAAGCCCTCGCCATGGACCCGCAGCAGCGGCTCCTCCTCGAAACCGCCTGGGAACTCCTCGAACGCGCCCACCTCGACCCCACGGCCCTCAAAGGCACCCCCACCGGCGTCTACACGGGCTGTGGTGTGCCCGGCTTCGGCACACCGCACATCGAGCGCAGCGCCGAGGGGTTCCTGCTGACGGGCAACGCGCTCAGCGTCGTGTCCGGCCGTATCGCCTTCACCCTCGGCCTGGAGGGGCCCGCGGTCACGCTGGACACGGCGTGCTCGTCCTCGTTGGTGGCGATGCACCTGGCGGTCCAGGCGCTGCGGCAGGGCGAATGCGATCTGGCCCTGGCCGGCGGGGTGACGGTCATGGCGACCCCGAACGTGATCACGGAGTTCTCCCGGCAGCGGGGCCTTGCCCCGGACGGCCGGTGCAAGCCGTTCGCCACGGCGGCCGACGGCACGGGCTTCTCCGAGGGCGCGGGCCTGGTGCTGCTGGAGCGGCTGTCGGACGCCGAGCGCAACGGGCACCAGGTGCTCGCCGTCATCCGGGGTACGGCCGTCAACCAGGACGGCGCGAGCAACGGGCTGAGCGCCCCCAACGGGCCCTCGCAGCAGCGGGTGATCCGCCAGGCGCTGGCCAACGCCGGGCTGGCCACGGTCGAGGTGGACGCGGTGGAGGCCCATGGCACGGGCACCACGCTCGGCGACCCGATCGAGGCCGAGGCGCTGCTGGCCACCTACGGCCAGGAGCGGGATGAGGACCGCCCGCTGTGGCTGGGGTCGATCAAGTCCAACATCGGCCATACGCAGGGCGCCGCCGGGATCGCGGGCGTCATCAAGATGGTGATGGCCCTGCGCCACGGCTCGCTGCCCGCCACCCTCCACGTCGACGAGCCCACCTCGCATGTGGACTGGAGCCGCGGCACGGTGCGGCTGCTGACCGAGCCGGTCGACTGGCCGGCGGCCCCCGACCGCCCGCGCCGGGCCGGCGTCTCGGCGTTCGGCATCTCCGGCACCAACGCCCACGTCATCCTGGAGGAGGCGGCCCGGCCCACGGCGGTGGAGGCACAGGGCGCCGCGCCGGAGGCCGAGGCGGAGACAGCGGAGGAGGAGGCCGCCGAGCCTGCCGTCCTGGGCGGCGTGGCGCCGTGGCTGCTCTCGGCCC GTACCCCACAGGCCCTGGCCGACCAGGCGCGGGGGCTGGCCCGGGCCGTCACCGGCACCGGCGCCCCGGGCGCCGCGCCCGCCGAGGTGGCCTGGTCGCTGGCCACCACCCGCGCCACGTTCGACCACCGCGCGGTGGTCACCGGCACCGAACTCGCCGACCTGACCGCCGCGCTCGATGCCCTGGCCACCGGCGGCGAACACCCCCGCCTCGTCCGCGGCACCGCCCTCGACCCACAGGCGGGCCCGGTCTTCGTCTTCCCCGGCCAGGGCTCCCAGTGGCCCGGCATGGCCGTCGGACTGCTGGACTCCTCGCCCGCCTTCGCCACCCGGATCGCCGCCTGCGAACGGGCCCTGGCGCCCTACGTCGACTGGTCGCTCACCGCCGTGCTGCGCTCCACCGACACCACCACCGACCCGCACCGCGTGGATGTCATCCAGCCGACCCTGTGGGCCGTCATGGTGTCCCTGGCGGGCCTGTGGCAGGACTTCGGCGTCACCCCCGCCGCCGTGATCGGCCACTCCCAGGGCGAGATCGCCGCCGCCTGTGTGGCCGGGGCCCTCACCCTCGACGACGCCGCCAAGGTGGTGGCCCTGCGCAGCCGGGCGCTGCGCGCCCTCGCCGGCCACGGGGCCATGGCCTCCCTCACCCTCGGCGCCGAGGACACCGCCCGCGTCCTGGCCGGACTCGGCCAGGCGGCCGAGGACGTCGCGGTCGCCGCCCACAACGGCCCCCGCTCCACCGTCGTCTCCGGACCGCCGGACCAGATCGCCACGGTCCTGGCGGCCGCCGAGGCACAGGGCGCCAGGACCCGCACCATCGACGTGGACTACGCCTCCCACAGCCCGCACGTCGACCGCATCCGCGACACCATCCTCGCGCAACTCGCCGACCTGGCCCCCACCACGCCCACCATCCCCTTCTACTCCACCGTCACCGGCGAGCAGCTGACCGGCACCCCGCTCGACGCCGAGTACTGGTTCACCAACCTCCGCCGCCCGGTCCGCTTCACCGACACCCTCACCGCCCTCCTGGACCACCACCACCGCCACTTCATCGAGGCGAGCCCCCACCCCGTCCTCACCCCCGGCATCCAGGACGCCATCGACGATGCCGACCTCCCCGCCACCACGATCCCCACCCTCCGCCGCGACCACGGCACCCCCCACGACCTCGCGGACGCCCTCGCGCTCGCCCACACCACCGGCCTCGCCGTCGACTGGCGGCCCTGGTACGCCGCCACCCCGCCCGCCACCACCGATCTGCCCACCTACCCCTTCCAGCGGCAGCGCTACTGGTCGGCGGCGGGCCGCCGGGCCGGTGACGTCAGCGCGGCCGGGCTGCGGCCGGTGGACCACCCGCAGCTGTCGGCCGCGACGGGCCTCGCCGACGGCGGGCTCCTGCTCACCGGGCGGCTGCCGGCGGCCGGGGACGCCGGCTGGCTGGGCGAGCACGAGTTCGCCGATGCGGTCCTGGTGCCCAGCACGGCCCTGGTGGAGTGGGCGCTGCGGGCGGCCGACGAGGCGGGCTGCGGCGGTGTCGAGGAGCTGACCCTTGAGGTCCCCCTGACCCTGTCCGCCGCCTCCGAGCTGCGCGTCCAGGTCGTGGTGGACGCCCCCGACGAGGACGGCCGGCGGGCCGTACGCATGTCCACCCAGCCCGCGGTCGACACACCGGACGGAGCCGACGGGCCGGACACCTGGACCTGCCATGCGACGGGCACCCTCACGGTCTCCCCAGCCGCCGGGACTGAGCTGGCGGGCGCCTGGCCACCGGCCGGTGCCGAACCGGTGGACCTCACCGGCCTGTACGCGCGCGCCGAGGCCGCCGGCTACCGGTACGGGCCGACGTTCCAGGGCGTCCGGGCGGTGTGGCGGCACGGCGCCGACCTCCTCGCCGACGTGGCCCTGGACCAGGGGGCCGAGGAGGGCGGCGACGAGTTCGGCATCCATCCCGCGCTGCTCGAATGCGCCCTGCACCCGGTGGCGCTGGACGACGCGGACACCGACGGCCCGCTGTGGCTGCCGTTCTCCTGGAGCGGCGTGTCCCTGCACGCGGGCGGCGCCACCGGCGTACGGGTCCGGATCGGACAGCGGGAGCACGCCGAAGGCCGTGAGCTGACCGTCGTCGTCGCGGACCCGGCCGGCGCCCCGGTGCTCACCGTGGATTCGGTCGCGCTGCGGCCCGCCGACGGAGACTGGCTGAAGGCCGCGGAACGCCGCTCCGCCGGCGGCCTGTTCACGGTGGAGTGGACACCGCTGCCGCCGCCGGAGAGCCGGCCCGAGCCGGGTGAGGCCGAGGAGCGCTGGGCGACGCTCGGCGACCTGGGCCCCGGGCGCCACTACGCCGACCTGGCCGCGCTGCTGTCGGCGGTGGACGAGGCAGAGCCCGCTCCGCCCGTGGTCCTCGCCGCCGTGCCACCTGCGGCCGGCTCCGGGGCCGACACGGCTCCGGTCACCGTCCGGCACACGTTGGAGCTGGTCCAGGGCTGGCTGGCGGAGCCGAGGTTGCGGGACTCCCGGCTGGTGCTGATCACCTCCGGCGCGGCCTCGGCCGGCGAGGACGACGGGCCGGTGGATCCGGGGAGCGCGGCCGTGCTCGGCCTCGTCCGGGCGGTCCAGGCCGAGCACCCGGACCGCTTCACGCTGGTCGACCTGGGCGCCGAAGCGGGCGCGGGCTCGGACTCGGGCACGGACTCGGGCACGGGCTCGGGCTCGGGGGCGGAAGAGACGTTGGTCGAGGCGGTGCGCCGGGCCGTCGCCGCGGACGAGCCGCAGATCGCAGTCCGTTCGGGCGCGGTGTCGGTCCCCCGCCTGGTACGCGCCGTCACCCGCCCCGATGAGGACACGGCGGTCGAACTGTCCGGCGGCACGGTGGTGGTGTCCGGCGGGGCGGACCACCCGGCCGGCGGCCAGGTCGCCGAGCAACTGGTGCGCGCGTACGGCGCCGAGCGTCTGCTGCTCCTCTCCCACCCGGACAGCGGGGCCCCCGGCGCGGCCGACCTGGCCGAGCGGCTGACGGCGCTGGGCGCCCGGGCGGAGGTGGCGGCGGTCGATGTCGCCGACCGCTCCGCTCTGGCGGAGGTTCTGGCCTCCGTGCCCGACAGCCACCCGCTGGTGGGCGTGGTGCATCTGGCCGGGGCGTCCGACGGCGCCCCGGTGGAGTCCTGGGACGACGGGCGAGTGTCGCGGGCGTGGGCGCCGGGGGCCACCGGCGTGTGGAACCTGCACGCCCTCACCCATGGCCTGCCGCTGCGGATGTTCGTGGTGTTCTCCTCCGCCGCCGATGTCACGGGCGGCCCCGGCCGGGCCGGACACGCCGCGGCTCACGCCCACACCGACGCGCTGATCGCCCACCGGCGCGCAGCGGGTCTCCCGGGTACGGGCCTGGCCTGGTCCCTGGGGGAAGAGGCCACTCCCGACGCCTCGCACCTGCTCGACGCGGCGTTGCACGCCGTACACCCCCTGGTCGTGGCGGCGGACCTGGACGTCGCCCGGCTGGGGCCCGCGGCTCCCGCGCTGCTGCGCGCCCTGG TCCGGCCCGGCCGGCGCCGCGCCGCGGAACGGCAGTCGGCGGTCCTCGCCCTGGCCTCGCGCCTCGACGGTCTCGACGCCTCCGGACAGCGCGAACTGCTGCTCGATGTGGTGCGCCGGATGGCCGCCGTGGTGCTGGGCCACTCCTCCGACGCGGCGATCCGGGCCGAGGCCGCCTTCAAGGAGCTGGGCTTCGACTCCCTCACGGCCGTCGGGCTGCGCAACCGCCTGGTCGACGCCACCGGGCTGCGGCTGCCCTCGACCCTCGTCTTCGACTATCCGACCCCCCGGGCCCTGGCCGACCACCTCCTGCAGCACCTGACCAGCACCGCGCCCGCCACGGCGGTGCCGGTGGGGCCGGCCCGGGCCGCGAGCGCGGACGACGAGCCCATCGCCGTGGTGGCGATGGCGTGCCGCTTCCCGGGCGATGTGACCACGCCCGAGGGGCTGTGGGACCTGGTCGCGGCGGGAGAGCACATCCTGGGGCCCTTCCCCACCAACCGCGGCTGGGACCTGGCCAACCTGTTCCACCCCGACCCGGAACACCCGGGCACGACCTACGCCTCCCAGGGCGCGTTCGTCTACGACGCCGACGGCTTCGACGCCGCGTTCTTCGGCATCAACCCCCGCGAGGCGCTGGCCATCGACCCCCAGCAGCGTCTGATCCTGGAAACCGCCTGGGAGGCCCTGGAACGCGCCGGTATCGACCCGCACACCCTCAAGGAGAGCCTGACCGGGGTCTACACCGGTGTCATCTACCACGACTACGCCGCCGGTCTGCCCGCGGGCGACCCCCGGCTGGACGGCTACACCATGCTGTCCAGCATCGGCAGCATCATCTCCGGCCGGGTGGCGTACACCCTCGGCCTCCAGGGCCCGGCCGTCACCGTGGACACCGCCTGTTCCTCCTCCCTGGTCGCCATGCACCTCGCCGCCCAGGCCCTCCGTCAGGGCGAATGCGATCTGGCGCTCGCGGGCGGGGTGACGGTCATGGCCACCCCTGACCCGTTCACCGGGTTCTCCCGGCAGCGCGGGCTGGCCCCCGACGGGCGGTGCAAGCCGTTCGCCGCCGCCGCCGACGGCACCAGCCTGAGCGAAGGAGCCGGTCTCGTCCTGCTCGAACGCCTCTCCGACGCCCGCCGCAACGGCCACCAGGTGCTCGCGGTGGTGCGCGGCTCGGCGATCAACCAGGACGGCGCGTCCAACGGGCTGACGGCCCCCAACGGCCCCTCCCAGCAACGCGTCATCGGCCAGGCCCTCGCCAACGCCGGCCTGGGCCCCGCCGACATCGACGCCGTGGAGGCCCATGGCACGGGTACGACGCTGGGCGACCCCATCGAGGCCCAGGCCCTCCTGGCCACCTACGGCCAGGACCGCCCCGAGGACCGGCCCCTGTGGCTCGGCTCGGTCAAGTCCAACATCGGCCACACCCAGGCCGCCAGCGGCATCGTCGGCGTCATCAAGATGATCATGGCGATGCGCCACGGACGGCTGCCCGCCAGCCTCCACATCGACGAACCCAGCCCGCACATCGACTGGACCAGCGGAAACGTCCAGCTCCTCACCGAGGCCACCGACTGGCCCGAGACCGGCCGCCCCCGCCGCGCCGCCGTCTCCTCCTTCGGCGCCTCCGGCACCAACGCCCACCTCATCCTCGAACAAGCCCCCCACCGGCCAGAACCCCGGCCGGTGGCCGGCACTCCCCCGCCCGGCACCGTCCCCTGGCCACTGTCGGCGCGCGACGACCAGGCCCTGCGCGAGCAGGCCGCCGCGCTCGCCGAGCAGCTGCGGGCCGACGGCAGCGCGTCGGTGGCGGCCGTGGGGTGGTCCCTGGCCACGACGCGGGCGGTGTTCGAACGGCGGGCCGTGGTCGTCGGCGAAGGCCTGGAGGAAATGACCGCCGCGCTGGAGGCGCTGGCCGCCGGCGATCCGCACCCCGGCCTGTCCACCCCCACCGGCGCCGGGTCAACGGCGCCGGGGAACGTGGTGTGGCTGTTCTCCGGGCAGGGCAGCCAGCGGCCGGGCATGGGCGCCGACCTCTACCGGCGCTTCCCGGTCTTCGCCGACGCCTTCGACGAGGTCTGCGCGCTCCTGGACCCCCACCTCGACCATCCGCTGCGCGAGGTGGTCTTCGCCACCGACCCCGGACACGGCGACCTGATCCACCACACCACCTACACCCAGGCCGGTCTCTTCGCCCTCCACCTCGCCCTCGCCCGCCTCCTGACGAGCATGGGCCTGGCCCCCGACGCCGTCGCGGGCCACTCCATCGGCGAGATCTCCGCCGCCCACCTCGCGGGCGTGCTCTCCCTGGAGGACGCCGCCCACCTGGTCGCCGTCCGCGCCACCCTGATGGGCGGTCTCCCGCCCGGCGGCGCCATGGCCACCGTCCACGCGAGCGAAGAGGAGATCACCGCCACCCTGGACGACCACCCCGGCCTGGCCATCGCCGCGATGAACACCCCGGGCCACACGGTCATCTCGGGCCCCGCCGACCAGGTGGCCGCCGCCACCGCGAAGTGGCGGGAACAAGGCCGCAGGACCCGCTCCCTCCCGGTCTCCCACGCCTTCCACTCACCCCTGATGGAGCCCATCCTCGCCCCCTTCACCGAGGCCATCGGCCATCTGACCTTCCACCCGCCCCGTACCCCGCTGATCAGCAACCTCACCGGCCGGCCCGCGGGCGAGGAGATCACCACCCCCGAGTACTGGGCCCAGCACATCCGCCGGCCGGTCCACTTCCACCAGAGCGTCAGCCACCTCGCCGAGGACACCGCCGTCTTCCTCGAGCTGGGCCCGGCTCCCGTGCTGACCCACGCCGTCCACCACACCCTGCCCGAGGAGACCAACGCCACCGCGCTGGCCACCCTCACCGGCAAGCAGCCCGATGTGCGGGCCCTGGCCCACAGCCTGGCGTCGCTGCACATCGCCCACGCCCCCCTGGACTGGACGCCCTGGTATCCCGCCGACCCGGCCCCCGAGACGGTCGCGCTGCCCACCTACCGCTTCCAGCGCCGGCCGTACTGGATCGCCCCCCACACCTCCGGCAACGCCGCCCCCGGCGGCACCGGCCTTGACCATCCGCTGCTGGACGCGGCGGCGCCCCTGGCGGACGGCGGCGTGGTGCTCACCGGGCACGTCCCACCGGCCGACCACGACAGCTGGCTCACCGAGCACACCATCGCCGAGACCGTCCTGCTGCCCGGCACCGCGCTCCTCGAACTCGCGCTGTGCTCCGCCGAGCACACCGACAGCCCCCACGTCGAGGAACTTCTCCTCCACCACCCGCTCACCCTCCACCCGACCTCCCCCCTCGATCTGCAGATCGTCGTCGGCACCGCCGATGACGCCGACCGCCGGGTCCTGCACATCTACACCCGCCCCCAGTCGGCCCCCGCGGCCGAGTGGACCCGTCACGCCACCGCCACCCTCGCCGCCGAGCCCGCCACCGGCCATCCGGCGCAGGTGCGGGAGGCGGCATGGCCGCCCGCCGGGGCCGAACCCGTCGACATCACGGGCTTCTACGACCGCGCGGCGGCGAACGGCTAT GCGTACGGGCCCGCTTTCCAGGGGCTCCAGGCGCTGTGGCGGCGCGGCGACGACCTCTTCGCCGAGGTCACCCTGTCTACGGGCGAGGCCACCGACGACACGGCCGAGGCCCTCACCGTCCATCCCGCGTTCCTCGACAGCGCGCTCCACCCGCTGGTCGCCGTCACGGACACCTCGGGCGGCGAGGTCTGGCTGCCGTTCTCCTGGAGCGGCGTCACCCTCCACGCCACCGGCGCCACCCACGCCCGGGTCAGGATCACCTCCCGCAACGAGAGCGAGCACAGCGTCACCCTCACCGACGCCACCGGGCAGCTCGTCCTCACCGCCGACGCCGTCACCACCCGGCCCATGCGCCTGGACGCGCCCCAACCGGCCACCACCGAGGGCCTGTTCACGCTGGAGTGGACGCCCGCGGCTCCCCTCGCCGAACGGGCGGAGGAGCCCGCACCGCCCGAGGTGGTCTTCGCCGAGGCGCCGGTCGCAGACGCTGACGGCGGCGAGCTGGAGGCCGTCGAGCGGGCGTTGGCGCTGGTGCGGAACTGGCTGGCCGAACCACGGCCCGACGACGCCCGGCTGGTGGTGCTGACCCGCAAGGCCGTGGCCGTGGACGAGGAGACGGACCTCGACCCCGTCGCGGCGGCCGTCTGGGGCCTGGTCCGCAGCGCCCAGTCGGAGAACCCCGGCCGCTTCGTCCTGCTGGACACCGACCTGCCCACGGACAAGGACACCGCTCCGGCGTCCGACGGCCGGGTGGCCGACGCGGTCCGCTGCGCGCTCGACCTCGACGAACCGCAGCTGGCGCTGCGCGGCGGCCGGGTCCTGGTGCCCCGGCTCGTCCGCGCCACCGCCTCGGCCGCGCTCGTACCCCCCGTCGGCCAGGGGGCGTGGCGGCTGGACGCCGCGGGCACGACGGGCTCCGCGACGATCGACTCCGTGGCGCCGGTGCCGTTCCCCGAGGCCGAGGAGGAGCTGGCGGCCGGGCGCGTACGCATCGAGGTGCGCGCGGCCGGTGTCAACTTCCGCGATGTCCTGATCAGCCTGGGCATGGTGCCCGACCAGACCCGCATCGGCGGCGAAGGCGCGGGCGTCGTCCTCGAAGTGGCCCCCGACGTCACCACGGTGGCGCCCGGCGACCGCGTCCTGGGCGTCTTCGACGGGGCGTTCGGCCAGGTCACCGTGGCCGATGCGCGGATGGTGACCAGGATGCCGGCAACCTGGGACTTCCCCCGGGCGGCGGCCGTCCCCGTGGCGTTCCTGACCGCGTGGTACGGGCTGGTGGAGCTCGGCCGCCTGAAGGCGGGCGAGTCGGTGCTCATCCACGCGGCGGCCGGCGGTGTGGGCATGGCCGCCGTGCAGATCGCCCGCCACCTGGGCGCCGAGGTGTACGGCACCGCTAGCCCCGGCAAACACGCCGCGCTGGAGGCCATGGGCATCGACGAGACCCACCGCGCCTCCTCCCGCGACCTCGACTTCGAGACCGCCTTCCGCGCCGCCACCGGCGGCCGCGGCGTCGATGTGGTCCTCAACAGCCTGGCGGGCGACTTCATCGACGCCTCGCTGCGTCTGCTGGCCAAGGGCGGCCGGTTCCTGGAGATGGGCAAGACCGACCTCCGCGACCCGGAGCAGGTGGCCGAGGACTTCGCCGGGGTGGACTACCGGGTGTACGACCTGGTCTCGGACGCCGGGGCGGAACGCGTCGCGCTGATGCTGGCGACCCTGGTGGAGCTGTTCGACGAGGGCGCTCTGACGCCGCCCCCGGTGCAGGCGTGGCCGCTGGCCAGGGCCCGCCAGGCGCTGCGCCACATGAGCCAGGCCAAACACACCGGCAAGATCGTCCTGACCGTCCCCCCTGCTCTCGACCCCGACGGCACGGCCCTGATCACCGGCGGCACCGGCACCCTCGGCGCCCTGGTCGCCGAACACCTCGTCACCACCCACCACATCACCCACCTCCACCTCCTCAGCCGCCGCGGCCCGGACGCCCCCGGCGCAGCCGACCTGACCGCCCGGCTCACCGAGCTCGGCGCCACCGTCCGCATCACCGCCGCCGACACTTCGGACCTGCGGGCCGTGCGGCAGGCCGTCGACGCGATCGACCCCGACCACCCGCTCACCGCCGTCATCCACACCGCCGGTGTCGTCGACGACGCGATGGTCACCTCCCAGACCCCCGACACCCTCCGCCGCGTCTGGGCGGCCAAGGCGGCGGGCGCGGCCAACCTCCACCGGGCCACCCGGCACCTCCCGCTGGCCATGTTCGCCCTCTACTCCTCCGTCTCCGGCACCCTGGGCAACCCAGGACAGGCCAACTACGCCGCGGCCAACGCCTACTGCGACGCCCTGGCCTCCCGGCGACACCACGCGGGACTGCCCGCCACCTCCATCGCCTGGGGGCTGTGGGACGCCACCAGCGACATCACGGGAGCGCTCACCGAGGCCGATGTGGCGCGGATGGGCCGCACCGGCGTCACGGCGCTGGCCACCGACCACGCGCTGGCCCTCTTCGACGCGGCCCACCGGCACGGGGACCCGCAGCTCGTGGCGCTCGACCTCGACGTCCACGCGCTGGCCGCACAGCCGGCGGCCACCCTCCCGGCCGCGCTGCGCGCCCTGGCCGCCCGCCCGAGCGGGGCCACGCGGCGCGCCGCCGCGGCCGCGCAGCGCCCCGACGACTGGACGCGCCGGCTCGCCGGACTCCCGGAGGCCGAGCAGCGGCAGCAGCTGCTCACACTGGTGCGCACGAACGCCGCGACGGTGCTCGGCCACGCCGACGCCGAGAGCGTACGGGAGGAGGCGCCGTTCACCGATCTGGGCTTCGACTCGCTGACCGGTGTCGAGCTGCGCAACCGGCTCTCGGCGGCGACCGGGCTGCGGCTGCCCGCCGCGCTGGTCTTCGACTTCCCCTCGGCCCGGGCGCTGGCCGACCATCTGCGCGGCCAGCTGGTGGCGGACGGGGGAGCCGGCGCCCAGGGCGGGGTGGACCCGGTGCTCGGCGAGCTGGCGCGGCTGGAGTCCACACTGTCGGCCCTCGACCTGCCCGAGGCGGACGCGCGGGCGGTGACAGATCGGCTTGAGGGTCTGCTGGCCCAATGGAAGGCGGCGTCCGCGCCGCCGGCCGAGGACAACGCGACCGACCGGCTCACGCTCGCCACCGCCGACGAAGTGCTCGCGTTCATCGACAACGAACTCGGCACCTCGTGAAGGCTCAGTTGCTCGCTTCGACGCGTATGAAGGTCGTGACTGCGGATGCCGGATGAAGAGAGGCTTGTCGACTACCTCAAGCGTGTGGCGACCGATCTGCACGACACGCGGCGGCGCCTGCGCGAGGTGGAGGAGCGGGCCCAGGAGCCCATTGCCATCACCGCGATGACCTGCCGGTTCCCCGGCGGGGTGGATTCGCCCGAGGCGTTGTGGGACCTGGTGGCCTCCGGTGTGGACGCCGTCGGGCCGTTCCCCGCCGACCGCGGCTGGGACCTGGACGGCCTGTACCACCCCGACCCCGACCACCCGGGCACCACGTATACGCGCG AGGGCGGGTTTCTGCGCGACGCCGACAAGTTCGACGCGGGCTTCTTCGAGATCAGCCCCCGCGAGGCGCTGGCCACCGACCCACAGCAGCGCGTACTGCTGGAGGTGGCCTGGGAGCTGTTCGAGCGGGCCGGTATCGACGCCACGGGCCTGCGGTCCAGCCGGACCGGTGTCTTCGTCGGGGCCGCCACCATCGGCTCGGCCACATCGGGTGTCCCCGTCCGCAAGGAGACCGAGGGGTACGCGGGCGTCGCCCCCAGCATGCTGTCGGGCCGGCTGTCGTACACCTTCGGCCTCGAGGGCCCCGCGCTGACGGTGGAGACGGCCTGCTCCGCGTCGCTGGTGGCGATGCATCTGGGCATTCAGGCGCTGCGGCAGGGCGAGTGCGAACTCGCGGTGGCCGGTGGCGTGACCATCATGGCCTCGCCCGCGGTGTTCACCGGCTTCGCCCGCCAGCGCGGTCTGGCGCCGAACGGACGCTGCAAGCCGTTCGCCGCGGCCGCCGACGGCACGGGCTGGGGCGAGGGCGCCGGTCTGATCCTGCTGGAGCGGCTGTCGGACGCCCGCCGCAACGGCCATCAGGTGCTCGCCGTCATCCGGGGCTCGGCCGTCAACCAGGACGGCGCGAGCAATGGCATCACCGCGCCCAACGGCCCTTCCCAGCAGCGCGTCATCCGCCAGGCGCTGGTCAACGCCCGCCTGTCGTCCGCCGAGGTGGACGTGGTGGAGGCACACGGGACGGGCACCCGGCTCGGCGACCCGATCGAGGCGGACGCGCTGCACGCGACGTACGGGCGGCAGCGGCCGGCCGACCGGCCGCTGCTGCTGGGCTCGCTCAAGTCGAACATCGGCCACACCCAGGCCGCGGCGGGGGCGGCGGGCGTCATCAAGACGGTGATGGCGATGCGCCACGGGACGATCCCCGCGACGCTGCACATCGACGAGCCGACGCCACATGTGGACTGGAGCTCGGGGGCCATCCGCCTGGTGACCGAGCCGGTCGACTGGCCGGAGACGGACCACCCGCGCCGGGCCGGGGTGTCCTCGTTCGGCGTGTCCGGGACCAACGCACATGTGATCATCGAGCAGGCACCCGACGCGGCCGAAACCACCCCGGCCGGCCCCGCCCCGGAGAGCCAGGAGGGCGCCCCGGAGGCGAACCGAGCCGCAATAAGAGGCACCGTGGTGCCGTGGGTGCTGTCCGCGCGGGGCGAGGCGGCGCTGGCGGAGCAGGCGCGGCGGCTGGCCGAGGCGGTGGAGCGCGATCCGGCCGCCGAGGTGGCGGACGTGGGCTGGTCGCTGGCGACGGCGCGGGCCCGGTTCGAGCACCGGGCCGTGGTGGTCGGCACGGACCGGTCGGCGCTGCTGGGCGGTCTGGCCAAGCTGGCCGCCGACGAGCCCGATCCCGCGGTGGTCACCGGCGCGGCGGGCCCGACGGGCGTCGGCCCGGTGTTCGTCTTCCCCGGCCAGGGGGCGCAGTGGCCGGGCATGGCGCGTGAACTCCTCGACTGCTCCCCGGTCTTCGCCGCCCGGATCGCCGAGTGCGAGCGGGCCCTGGCGCCGTACGTGGACTGGTCGCTGACCGCCGTGCTGCGCGGCACGGACGGTGCGACGGACCCCAAGCGGGACGATGTCGTCCAGCCCGTGCTGTGGGCCGTACACGTCTCGCTGGCCACGCTGTGGCAGAGCTTCGGCATCACCCCGGCGGCCGTCGTCGGGCACTCCCAGGGCGAGGTCGCCGCCGCGTGTGTCGCCGGGGCCCTCACCCTGGACGACGCCGCCAGGATCATCGCCCTGCGGGTCCAGGCCCTGCGCCCGCTGATCGGCCACGGCGCCATGGCCTCCCTCACGCTGAGCGCCGAGGACACCGCCCGGCTCATCGGCGACCTCGGCCCGGCGGCCGGGGACGTGGCCGTCGCCGCCGTCAACGGCCCGCGGGCCACGGTCGTCTCCGGCTCCCCGCGGCCTCTGGCCGCCGTGCTGGCGGCGGCGGAGGAGCGCGGCGCGCGCACTCGGACCATCGACGTGGCGTACGCCTCCCACGGCCCGCACGTGGACCGCATCCACGACGACGTCGTCTCGGCGCTGGGTGAGGTGTCCCCGGTCGAGTCCGAGATCGCGTTCTACTCCACCATGACCGCGGAACGCCTGAACACCGCGGGGCTCGACACCGAGTACTGGTTCGACAACCTCCGCCGGCCGGTGCGTTTCGCCGAGGCCGTGGACCGGCTGCTGGCCGACGGATACCGGGTGTTCATCCAGTGCAATCCGCACCCCATCCTGTCCACGAGCCTGCAGGAGACCTTCGAGGAGTCCGGCGTCCCCGCCACCTCCCTCGCCACCCTCCGCCGCGACCACGGCGGCGCGCACCAGCTGGCCCTCGCGCTCGCCGAGGCGCACGCCGCGGGTCTCGGGGTCGACTGGCGCCCCTGGTTCGCGGGCGACGGCGTCCCCCGCACGGTCGAGCTGCCCACCTATCCCTTCCAGCGCCGCCGTTACTGGATACCGTTCGGCGGAAAGGGCACCGGCGACATGTCCGCCGCCGGTCTGCGCGCGGTGGAACATCCGCTGCTGGCCGCCGCGGTGAGCCTGCCCGACGGCGGCATGGTGCTGACCGGGCGCCTTCCGGCCACGGGCGACGGCTGGCTCGCCGACCATGTCGTCGGCGGCACCGCGCTGCTGCCCGGGGCGGCCCTGGTCGAGTGGGCGCTGCAGGCCGCGCACGAGGCGGGCTGCGCCGCGGTGGAGGAGCTGGCCCTGCGGATCCCGCTCGTGCTGCCCGCCTCGGGGGCCCTGCGCATTCGTGTCGCCGTGGGGCCCGCCGACGACGACGGCAGGCGGACCGTGGATGTGCACTCGCGCCCCGACGAGCTGGACACGGAGGCGCCCGACGGGTGGGTGTGCCACGCCATGGGCACGCTCGCGCCCGAGGACGCCGCGGACCCGGCCGCCCCGCCGGACACCGCGGCGGCGCCCTGGCCACCGCGGGCGGCGGAGCCGCTGGACGTCGCGGACTTCTACGAACGGGCCGCGGACGGCGGCTACGGCTACGGCCCCGCGTTCCGCGGTCTGACCGCGGCGTGGCGGGACGGCGCCGATCTGCTCGCCGAGATCGCGCTGCCCGAGGCGGCCGGCGAAGGCCCCGACCGGTTCGGCATCCACCCGGCGCTGCTGGACGCGGCCCTGCACCCGACGCTCCTGGACGGCGGCCGTCAGGGCGCGTCGCGGGACGGTCAGGTGTGGCTGCCGTTCGCCTGGAGCGGCGTGTCGCTGTGGGCCACGGGGGCGCGCCGCGTACGGGTGCGCGTATCCCCGCTGGAAGGCGGGCGGCGGATCTCGCTGACCGACGAGACCGGCGCGCCGGTCCTGGACGCCGAGTCGGTCTCCGTACGCCCCACCGGCGTCGCCGAGCTGCGCGCCATCGGCGAGCGCGCGGCCGAGGGCCTGTTCGTCGTGGACTGGGTGCCCGCGCGTGGCGGGACGGGCGACGCGCCGGCGCTGCCGGACGACGGCTGGGCGATCATGGGCGACGGCT GGGGAGCAGCGGGCGACGGTGGCGTACTCGCCGGGGTGGCGGCCCACGCCGACCTCGGCGCGCTGCTCGCCGCGGTGGACGACGGGACCCCGGTGCCGACGGTCGTCCTCCACCCGGTGACAGCGCCTGCCGCCCCCGACGGCGGCCTGGCCGCCGTCGGGGGCGTGCTGAGCCTCGTCCAGGGGTGGCTGGCGGAGCCGCGGTTGGCGGACTCCCGGCTGGTCCTGGTCACCTCGGGCGCCGTGTCGGCCGGCGACGACGAGGGGTCGGTGGATCCGGGCGGCGCGGCCGTGTGGGGTCTGGTCCGTTCGGTCCAGGCCGAGCACCCGGGCCGGTTCACCCTGGTCGACACGGCCGGTGCGGCGGACGGGGACCGGCTCCTGGCCGAGGCGGTGCGCCGGTCTCTCGACGCCGACGAGCCGCAGGTGGTCGTGCGCGCGGCCGGAGCGCTGGTGCCGCGCCTGGTGCGCACCTCTCCGTCGGCCGAGGACGAGGCCCCGGAGCTGTCCGGTGGCACGGTGGTGGTGTCGGGCGGGACGGGGGTGCTGGGCGGTGAGGTCGCCGAACACCTGGTGCGTACGCATGGGGTGGAGCGTGTGCTGCTCCTGTCCCGGCGCGGCGCCCAGGCGCCCGGCGCGGCCGAACTCGTGCGGCGGCTGGTCGACTTGGGGGCCGAGGCGGAGGTGGCGGCGGTCGACGTGGCCGACCGCGCCGCGCTGGCCGAGGTGCTGGCGGCGGTCCCCGAGGACCACCCGCTGGTGGGTGTGGTGCACGCCGCCGGTGTGATCGACGACGCCCTGGTGGAGTCCTGGGACACCGGCCGGCTCGCCCGCGTCTGGACCCCCAAGGCCCTCGGCGCGTGGAACCTGCACACTCTCACCCGTGATCTGCCGCTGCGGCTGTTCATGGTGTTCTCCTCGGCCGCCGGCGTCGTCGGCAACTCCGGCCAGGCCGGATACGCCGCCGCCAACGCGTACACCGACGCCCTGATCGCCGACCGCCGCGCGGCCGGGCTGCCCGGCACCTCGATCGCGTGGACCCTGTGGCAGCAGACCTCGGCCATGACCGAGCACCTGACCGAGGCCGATCTGACCCGTCTGGGCACCCTCGGCATGCGTCCCCTCGCCACGTCCCGTGGCCTCGGGCTCCTCGACGCGGCGCTCCATGTCGCCCACCCGCTGGTGGTGGCCGCCGACCTCGACGCCACCCGGCTCGGCCCCGACGCCCCCGCCATGCTGCGCGCCCTGGCCAGGCCGGCCCGCCGCCGCGCCATGGAACACCACGCCACCGGCCCCAAGCTGGCGGGCCGGCTGGCCGGTCTCGACGACACCGCCCGGCGCGATCTGGTGCTCCATACGGTGCGCCAGATGGTCATGGTGGTGCTGGGCCACTCCTCGGACGCGGCGATCCGCGCCGAGGCCGCGTTCAAGGAGCTGGGCTTCGACTCGCTGACCGCCGTCGAGCTGCGCAACCGCCTGGCAGGCGCCACCGGGCTGCGGCTGCCCGCCACCCTGGTCTTCGACTATCCCACCCCCCAGGCCCTCGCCGACCACCTGTTGGAGCGGCTGACCGCCACCGCCGCGCCCGCGCCCCGCGGTGCCGCGCCGTCCAGGGCCCGGGCCGCCGACGAGCCGGTCGCGGTGGTGGCGATGGCGTGCCGCTTCCCCGGTGGCGTGAGCTCGCCCGAGGGGCTGTGGGACCTGGTCGCGGCGGGACAGCACGTACTCGGGCCCTTCCCCACCAACCGCGGCTGGGACCTGGCCAACCTGTTCCACCCCGACCCGGAACACCCGGGCACGACCTACGCCTCCCAGGGCGCGTTCGTCTACGACGCCGACGGCTTCGACGCCGCGTTCTTCGGCATCAACCCCCGCGAGGCCCAGGCCATGGACCCCCAGCAGCGCGTCCTGCTGGAGACCGCCTGGGAGCTCCTGGAGCGCGGGGGTATCGACCCGCACACCCTCAAGGACAGCCTGACCGGCGTCTACACCGGCGTCATGTACCACGACTACGGCAGTGGTCTGCCCGCCGGGGACCCCCGGCTGGACGGCTACGGCAATCTCGCCGGCACCAGCAGCATCATCTCCGGCCGGGTGGCCTACACCCTCGGCCTCCAGGGCCCGGCGGTCACCGTGGACACCGCCTGCTCGTCGTCGCTGGTCACCATGCATCTGGCCGCCCAGGCGCTGCGGCAGGGCGAATGCGATCTGGCGCTGGCGGGCGGGGTGACGGTACTGGCCACCCCCGATGTGTTCACCGGCTTCTCGCGGCAGCGCGGGCTGGCCCCCGACGGGCGGTGCAAGCCGTTCGCCGCCGCCGCCGACGGCACGGGCTTCGGTGAGGGCGTCGGCCTGGTGCTGCTGGAGCGGCTGTCGGACGCCCGGCGCAACGGGCGGGTCATCCTGGCCGTCATCCGGGGTTCGGCGGTCAACCAGGACGGCGCGAGCAATGGGCTGACCGCCCCCAACGGCCCCTCCCAGCAGCGGGTCATCCGCCACGCCCTGGCCGGCGCGGGGCTCACCCCGGCGGATGTGGACGCCGTGGAAGCCCATGGCACGGGTACGACGCTGGGCGACCCCATCGAGGCCCAGGCGCTGCTGGCCACCTACGGCCAGGACCGCCCCGACGACCGGCCACTGTGGCTGGGTTCTGTGAAATCGAACATCGGGCACACCCAGGCCGCCGCCGGTGTCGCGGGCGCCATCAAGATGATCATGGCGATGCGCCACGGACGGCTGCCCGCCAGCCTCCACATCGACGAACCCAGCCCGCACATCGACTGGACCAGCGGAAACGTCCAACTCCTCACCGAGGCCACCGACTGGCCCGAGACCGGCCGCCCCCGCCGCGCCGCCGTCTCCTCCTTCGGCGCCTCCGGCACCAACGCCCACCTCATCCTCGAACAAGCGCCGCACACACACCAGCCGGTGGCCGACACTCCCCCGCCCGGCATCGTCCCCTGGCCGCTGTCCGCCCGGAGCGATGACGCCCTGCGCGCCCAGGCCACGGCGCTCGCCGAGCGGCTACGAGCCGATGGCCGGCCCGCCGAGCCCCTGTCGGTCCCGGGCGTCGGGCGGGCCTTGGCCGCGACGCGTTCGGTGTTCGAACGACGGGCGGTCATCGTCGGCAGCGACCAGCAGGAGATGACGGCCGCCCTGGACGCCCTGGCCGAGGGGCGCCCCCACCCCGGGCTGATCACCGCCGCGCCAGGCGCCACGCCCACATCAGGCCGGACCGTATGGCTGTTCTCCGGACAGGGCAGCCAGCGCCCCGGCATGGGCGCCGACCTGCACGGGCGATTCCCGGTCTTCGCCGAGGCCTTCGACGAAGTATGCGCGCTGCTCGATCCGCACCTGGACCACCCGCTGCGGGACATCGTCTTCGCCACCGGCGACGAGACCGCCGACCTCATCCACCACACCACCTACACCCAGGCCGGTCTTTTCGCGGTGCAGGTGGCACTGGCCCGGCTGCTGAAGGAGTGCGGTGTGCGGCCGGATGCGGTGATCGGCCACTCGATCGGCGAGATCACCGCCGCC CATATCGCCGGAGTCTTCTCCCTCGAAGACGCCTGCCGCCTGGTCGCCGCCCGCGCCACCCTCCTGGGCAGTCTGCCCCCCGGCGGCGCCATGACCGCCCTCGAAGCCACCGCCGAGGAGGCCGCCGAAGCCCTCGCCCCCTACGACGGCCAGGTCGCCATCGCCGCCCTCAACGCCCCCACCAGCACCGTCATCTCCGGCCCACTGGACCTGGTGACCAAGATCGGCACGGCGTGGAAGGAACGCGGACGCAGGACCAAGGCGCTGACCGTCAGCCACGCCTTCCACTCCCCCCTGGTCGAACCGGTCCTGGACGACTTCCGCGACGCCGTCGCCGAGCTGACGTACCACCAGCCCAGCGTCTCCCTCATCAGCAACGTCACCGGCGAACCGGCCGACGAGACCATCACCACCCCCGACTACTGGGTGCGCCACATCCGCCAACCCGTCCGCTTCCACCCCGCCATCACACACATCGCCCCGCACACCGCCGCCTTCCTCGAAGTCGGCCCCGACGCCGTCCTCGTCCCCGCAGCCCAGGACGCCCTCGACGCGCTGGACGACCTGCCCGCACACCCACCCCTGCTGATCCCGACCCTGACCCGCGGCCAGCCCGACATCCGCGCCCTGGCCCATGCCCTGGCCCGGCTGCACACCCACGCCCCCGTCGACTGGGCCCCCTGGTACCCCGCCGGCCCCACGCCCCCTGGCGTCGACCTGCCCACCTACCCCTTCCAGCGCCGGCCCTACTGGCTGACCCCGACCCACGCGGGGCCGGCCACCCCCGGCGCCGCCTCGCTCACCCACCCCCTCCTCGCCGCCACCGCGCCGCTCGCCGACGGCGGCATCCTCCTGACCGGGCAGGTGCCCGCCGCCGGCCACGAGGGCTGGCTCAGCGAGCACACCATCGCCGGCGCGGTCCTCCTGCCCGCCACCGCCCTCCTCGACATCGCCCTGCACGCCGCGGACCACGCCGCCACCCCCCACATCGACGAACTCCTCCTCCAACAGCCCCTCACGCTCGACCCCACGCACCCGCTCTCACTCCAGGTCATCGTCAGTCCACCCGACGACACCGGTCACCGCACCCTGGACATCTACGCCCGCTCGCAGTCCGGCCCCACGGCGGAGTGGACCCACCACGCCGCCGCCACCCTCACCGACGAGCCCACGGCCGCGCCGCCCCGGGACGGAGCGGAGGCGGCCTGGCCACCCCCGGGAGCCGAACCCGTCGACATCACCGGCTTCTACGACCGCGCCGCCGCGGGCGGCTACCACTACGGACCCAGCTACCAGGGCCTGCGGGCCGTCTGGCGCCACGGCGACGACCTCCTCGCGGACATCGAGCTCCCCGCCGCCGACGCCACCGACCCCACCGCCGATCCCCTCGCCCTCCACCCCGCCCTCCTCGACGCCGCGCTCCACCCGCTCCTCGCCACCGCCGACAACCCGGCCGGCGAGATCTGGCTCCCCTTCAGCTGGGGCGGTGTCACCCTGCACGCCACCGGCGCCACGCGGGCCCGCGTCCGGATCACCCGCCGTGGCGACAGCGAGCTCGGCCTGGCCCTCCTGGACACCACCGGGCGGCCCGTTCTGACCGCCGACACCATCACCACCCGGCCCATCGACACCGCGCGCCTGCGGACCAGCGGGCCGAACGACGGTCTGTACCAGGTGCGGTGGATCGCGCTCCCGATCCCGGCGGAGCCGCCGACGGCCGAAGCGGACGGCTGGGCGGTGCTCGGGGACGGCCGGCTCGACGAGGCGGTGCCGTCGCTGTCCCGGTATCCGGATGTCGCCGCGCTGATCGCGGCCATGGACGACGGCGCGCCCGTGCCGCAGACCGTCCTGACCGGCCCGGCACCCGCCGAGGGCGGCAGCGACGGCGACGGCTCCGATGTGGTGGCGCGGGTTCTGACGACGGCGCAGGAGTGGCTGGCCGAGCCGCGGCTCGCCGGCTCCCGGCTGGTGGTCGTCACCCATGACGCCGCCGCCGTGGCGCAGGACACCCCCGCCGGCCCGGAGGGCGGCGCCGTGGATCCGGTGGCCGCGGGCGTATGGGGGCTGGTCCGCAGCGCCGAGGCGGAGCACCCCGGCCGGTTCGCGCTGCTCGACCTCAGCGGCCGCGACGCCGGTCCGGCACCGGATGTCGTGGGGGTGCTGGGCGCGGCCCTCGCCGCGGACGAGTGGCAGGTGGCCGTGCGCGGCGGGGCGGCGTGGGTGCCGCGGCTGACGGCCGCGGACGCGACCGCCGACATCGTGCTGCCCGTGACCTCGTCCGCCTGGCAACTCGTCATGGCGGACGAGCACGCCGGAACGGTCGACGGGGTGGCGCCGGAGGAGTGCCCCGAGGTGCTGGAGCCGCTGGCGCCCGGGCAGGTGCGCATCGCGGTCCGCGCCGCGGGCGTCAACTTCCGCGATGTGATGGTGACCCTGGGCGTCGTGCCCGACCGGCGCGGGCTGGGCGGCGAGGGCGCGGGCGTGGTGCTGGAGGTGGCCGGGGACGTCACGTCGGTGGCCGTCGGCGACCGCGTCATGGGCCTGTTCCAGGGCTCGTTCGGGCCCGTGGCCCTCGCCGACGCGCGCGCCGTCGTCCCGATCCCGCCGGGCTGGACCGACCGGCAGGCCGCGGCCGTGCCCATCGCGTATCTGACCGCCTGGTACGGACTGGTGGACCTCGCGGGCCTCAGGGCGGGCGAGTCGGTGCTCATCCATGCCGCCACGGGCGGCGTGGGCACGGCGGCCGTGCAGATCGCCCGCCACCTGGGTGCCGAGGTGTACGCCACGGCCAGCCCCGGCAAACACGCCGCGCTGGGGGCCATGGGCATCGACGAGCCCCACCGCGCCTCCTCCCGCGACCTCGACTTCGAGGAAGCCTTCCGCACCGCCACCGGGCCCGAGGGCATGGACGTGGTGCTTGACTGCCTGGCGGGCGAGTTCGTGGACGCCTCGCTGCGGCTGCTGGGCCCCGGTGGCCGGTTCATCGAGATGGGCAAGACCGACATCCGCGACCCCGAGCAGATCGCCGACGCCCATCCCGGCGTCCACTACCGCGCGTACGACCTGGTCTCCGACGCCGGCCCCGACCGGATCTCGGAGATGCTGGACACGCTCGCCGACCTCTTCGCGCGGGGCGTCCTGGCGCCGCCCCCGGTGCAGGCGTGGCCGCTGGCCAGGGCCCGCCAGGCGCTGCGCCACATGAGCCAGGCCAAACACACCGGCAAGATCGTCCTGGACATTCCCCCCGCCCTCGACCCCGACGGCACCGTCCTGATCACCGGCGGCACCGGCACCCTCGGCGCCCTGACAGCCGAACACCTCGTCACCACCCACCACATCACCCACCTCCACCTCCTCAGTCGCCGGGGCCCGGACGCCCCCGGCGCAGCCGACCTGACCGCCCGGCTCACCGAGCTCGGCGCCACCGTCCGCATCACCGCCACCGACACCACCGATCCCCAGGCCCTTGGGCAGGCCCTCGACACCATCGACCCCGAGCACCCCCTCACCGCCGTCGTCCACACCGCCGGCACCGTCGAGGA CGCCGTGCTCACCTCTCAGACCCCCGACACCCTCCGCCGCGTCTGGGCGGCCAAGGCGACGAGCGCGGCCAACCTCCACCGGGCCACCCAGGACCTCCCCCTGGCCATGTTCGTGATCTTCTCCTCGGCCGCCGGCACCCTCGGCAGCCCCGGGCAGGCCAACTACGCCGCCGCCAACGCCTACTGCGACGCTCTCGCCACCCAAAGGCACCACGCGGGACTGCCCGCCACCTCCATCGCCTGGGGACTGTGGGCCGCCACCAGCGGCATGACCGGAGCGCTCACCGAGGTCGACCACGCCAGGATGAGCCGGTCCGGGATGGTGCCGCTGGCCACCGACCACGCCCTGGCGCTGTTCGACGCGGCACACGCACACGGCATGGCGCGGCTGCTGGCCGCCCAGCTCGACCTGGCGGCGCTGTCCGCCCAGCCCGCCGAGGCGCTGCCGCCGCTGGTCCGTTCGCTCACGAGCGCCGGGGCCCGGGTCGTACGGCGGTCCGTGGCGGCGCCGGTGGCCGACCTGTCCGGCCGACTGGGGTCGATGGGCGCCGACGAACAGCTGGCGCTCCTGCTCGATCTGGTCCGCACCCACGCGGCCACCGTGCTGGGGCACGCGGACCCCGGGGCGGTGGCGATGGACACGCCGTTCAAGGATCTCGGGTTCGACTCGCTGACGGCGGTCGAACTGCGCAACCGGCTCACCATGGCGACGGGGCTGCGGCTGTCCGCCGCGTCGGTGTTCCGCCACCCGACGCCCGCCGCCATGGCCGAGCACCTGCGGGGCGAGCTGTGCCCGGCGGAGGACGACGCGCTGCGGCCCGTGCTGCGGGAGCTGGAGCGGCTGGAGGCGGCGGTGGGCGAGGTGAAGCCGGAGGGCGAGACCGGTGCCCAGCTCGTCAAACGGCTGCAGTCGCTGTTGTGGCGGCTGGGCGACGGCGCCTTGGGGGTCGATCACACCGTCGACGGCGAGGCGCTGGAGTCGGCCTCGGACGACGAGATGTTCGCGCTCATCGACCAGCAACTGGGCTCGTCCTGACCGGCAGCGAGGGAGAAGCCATGTCCACCACCGAAGACAAGCTGCGCCAGTACCTCAAGCGCGTCACCTTCGACCTCGGCCAGGCCAAACAGCGGCTGCGCGAAGCGGAAGAGCGCCACCAGGAGCCCGTCGCGATCACCGCCATGGCCTGCCGCTACCCGGGTGGGGTCACCTCCCCGGAAGCCCTGTGGGAGCTGGTGGCCGACGGCACCGACGCCATCGGCCCCTTCCCCACCAACCGGGTCTGGGACCTCGACCGCCTGTACCACCCCGACCCCGACCACTACGGCACCAGCTATGTGACCGAGGGCGGCTTCCTGCACGACGCCGACCGGTTCGACGCCTCCTTCTTCAACATCAGCCCCCGCGAGGCCCTGGCCATGGACCCCCAGCAGCGCGTCCTGCTGGAGACCGCCTGGGAGCTGCTGGAGCGCGCGCGGATCGACCCCACCAGCCTCAAGGGCTCCGCCACCGGCGTCTACACGGGGGTGTCGAGCCAGGACTACCTGTCGCGGATACCGCGGATCCCCGAGGGGTTCGAGGGCTATACGGCCACGGGCGGACTGACCAGCGTGGTGTCCGGCCGCGTGGCGTACACGCTGGGTCTGGAGGGCCCGGCGGTCACCCTGGACACGGCGTGCTCGGCGTCCCTGGTGGCGATGCACCTCGCCGGGCAGGCGCTGCGGCAGGGCGAGTGCGACCTGGCCCTGGCCGGCGGTGTGACCGTGTTCAGCACTCCCACCGCGTATGTGGAGTTCTCCCGGCAGCGGGGGTTCGCGCCGGACGCCCGCTGCAAGGCGTTCGCCGCGGCCGCGGACGGCACCGGTTTCTCCGAGGGCGTGGGCCTGGTGCTGCTGGAGCGGCTGTCGGACGCCCGGCGCAACGGCCATCGCGTGCTCGCCGTGCTACGCGGCTCGGCGGTCAACCAGGACGGCGCGAGCAACGGGCTGTCCGCGCCCAACGACGCCGCCCAGGAACGTGTGATCCGGCAGGCGCTGGACAGCGCCCGGCTCACCGCCGACCAGGTGGACGCGGTGGAGGCGCACGGCACGGGCACCACGCTCGGCGACCCGATCGAGGCCCAGGCGCTGCTTGCCACCTACGGCCAGGACCGCCCGGCGGACCGGCCGCTGTGGCTGGGGTCGGTGAAGTCGAACATCGGGCACACCCACGCGGCGGCGGGCGTGGCGGGCGTGATCAAGATGGTGATGGCCCTGCGCCACGGCCGGCTGCCCGCCACCTTGCACATCGACGAGCCGACCTCCCATGTGGATTGGGACTCCGGCGCCGTACGGCTGCTGACCGAGCCGGTCGACTGGCCGCGGGGGGACCGTCCGCGCCGGGCCGGTGTGTCCTCGTTCGGCATCTCCGGCACCAACGCCCACGTCATCCTGGAGGAGAACACCCAGCCCGCCGGCACTCCCCCGGACGCGGCCGGCGAACGGCCCGAGGACCGGGTCACGCCGTGGGTGGTCTCGGCGCGCGGCGCGGACGCGCTGCGCGCCCAGGCCGGGCGGCTGCTGGACGCGGCGGCTCTCGACGGCGATCCGGACGCGGTGGGCTGGTCGCTGGCCACCTCGCGCACGGTCTTCGACCACCGGGCCGTGGTCATGGGCCGGGACACCGCGGCGCTGCGGGCGGGCCTGGCCGCGCTGGCGGCCGGGGAGGACCATCCGGCGCTGGTACGGCGCGAGGCGGGGGTGCGGGGCTCCGGGTGGCGGGTGTTCCTCTTCTCCGGGCAGGGCAGCCAGCGGCCGGGCATGGGCGCCGACCTCTACCGGCGCTTCCCGGTCTTCGCCGAGGCCTTCGACGAGGTGTGCGCGCTGCTCGATCCGCAGCTGGCCCACCCGCTGGCCGATGTCGTACTGCGCGGCCGGCCGCGAGCGGACCTGCTGAACCACACCACCTACACCCAGGCCGGGCTGTTCGCCGTGCAGGTCGCACTGGCCCGGCTGCTGAAGACCTGCGGCACCCGCCCGGACGCGGTGATCGGCCACTCCATCGGCGAGATCGCCGCAGCCCACATCGCCGGAGTCTTCTCCCTCCAAGACGCCTGCCACCTCGTCGCCGCCCGAGCCACCCTCCTCGGCAGCCTGCCCCCGGGCGGCGCCATGACCGCTCTCGAAGCCACAGAAGAAGAAACCACCGAAGCCCTCGCCCCGTACGACGGCCAGGTCACCATCGCCGCCCTCAACGCCCCCACCAACACCGTCATCTCCGGACCGGCCGACCTCGTCACCGAAATCGGCACGGCCTGGAAGGAACGCGGACGCCGAACCAAAGCCCTCACCGTCAGCCACGCCTTCCACTCCCCCCTGGTCGAACCGATCCTGGACGACTTCCGCGACGCCATCGCCGGCCTGACCTACCACCAGCCCACCATCCCCCTCATCAGCAACCTCACCGGCGAACCAGCCGGCCAGGACATCACCACCCCCGACTACTGGGTGCGCCACATCCGCCAACCCGTCCACTTCCACCCCGCCGTCACACACATC GCCCCGCACACCGCGGCCTTCCTCGAAGTCGGCCCCGACGCCGTACTGATCCCGGCCGCGCAGAACACCCTCGACGCGCTGGACGGCCTGCCCGCGCACCCTCCCCTGCTGGTCCCGGCCCTGACCGGCAAGCAGCCCGACGTCGAGGGCCTGGCCCACGCGCTCGCCCGGCTGCACACCCTCACCCCCGTCGACTGGCGCCCGTGGTTCACCGACGGTGCCCCGCCGCCGACCGTGGACCTGCCCACCTACCCCTTCCAGGGCGAGCGGTACTGGCTGCCGGACGCCCTGGCGGACGCGCCGCCGGCGGAGGCGGACGAGGAGGAGGTCCGGTTCTGGAGCGCGGTGGAGGCGCAGGACCTCCCGGCGCTGTCCGAGGCGCTGGGCATCGGCGAGGAGGACGGGCGGCGCTCGTCGCTCGGCGCGGTGCTGCCGACGCTGTCGCGCTGGCACCGGGAGCGCCATGAGCGGTCGACCCTGAGCTCCTGGCGCTACCGGGTCGGCTGGCGCCGGCTGCCGGAGCTCGGCCCGGCGGCCACGGCGGGCCCGTGGCTGCTGGTCGTACCCCCCCGGGGCGCCGGGGAGGCCGAGGAGTGGGCCGACGCCTGTGAGCGGGCCCTCACGGCGGACGGCGGTGCGGTGTGGCGGCTGGTGACGGACGGCCGGGCGGAGGTGGCCGGGCTCGCCGCGTCGCTGCGGGTGCTGTGCGACGAGGGCGGGGCCCCGGCGGGGGTGCTGTCCCTGCTGGCGCTGGACGAACGCCCACACGAAGCGTTCCCGGCCGTGATCGGGGGTGTGACGGGCACCCATGTGCTGCTGCGGGCCCTGCTGGAGGCGGGGCTCGACGCGCCCCTGTGGTGCGCCACGCGGGGCGCGGTGGCCGTCGCGGACGGCGAAGGGTCACAGGCGCCCGCGCAGGCCCAGGTGTGGGGGCTCGGCCGGGTGGCCGCGCTGGAGCATCCGGCGGCGTGGGGCGGGCTGGTCGACCTGCCCGCCTCGCCCGAGGACCTCGCCCCCGATCTGCTGCGCGCCGTGCTGGCGGGGCGGGCCGGGGAGGACCAGGTGGCGCTGCGGCCGGCCGGGGCCTTCGGGCGGCGGCTGCTGCCCGCACCACTGAGCGGCCTCGGGGAGGCGCCGGCGCGTGAGTGGACTTCCCGGGACGGTGTGCTGGTCAGCGGCGGGGTCGCCGGGACCGCGGCTCTCGTGGCGCGGTGGCTGGCCGCGGGCGGCACCAAGCGCCTCGTCCTGCTGGCGCCGGACGGCCCGGCCACGCCCGGTGGCGCGGAGCTGGTGGCCGAACTGGCGGAGCTGGGCGCGGAGGCGACGGTGGTGGACGGCGTGCCGTCCGAACCCATGGCGCGGCGGCAGCTGGCCGACCGGCTCGCGGCCTCGGGGCTGCGGGTCCGTACGGTCGTCCACACCGGGGCGCCGAGCGACTGGGCGCCGCTGGCGGAGTTCACGCCGGACGGGCTGGCCGAGGCGGTGTCGAACGCCATGGGGGGAGCCGACCGGCTCGCGGAGCTGTGCGGCCTGGAGCCCGACGATCCGGTGGTGGTCTTCTCGTCCATCGCCGCGGTCTGGGGCGGTGGCGGGCATGGCGCCCGGGCTGCGGCCGACGCGTATCTGGACGCGGTGGCGCGGCGCCGTCAGGCGGCCGGCGGCCATGTCGTCCGGCTGGCGTGGGGCGTGTGGGACGGTTCGGAGGGCCCGGAGGCGGCCGAGCGCGCCGAACGGCTGGGGCTGCCGGCCCTCCCGCCCGAGCTGGCGCTCGCCGCGCTGCGGCGCACCCTCGACGAGGGCGGTCACGGCGGCGAGCAGTGCGACGCCGAGGGCACCCGTGAAGGGCGGGGCGACGCGCACGCGGTGGTCGCGGACATCAACTGGGAGCGTTTCGTCCCGCTGTTCACCATGGCGCGCCCCAGCCGTCTCTTCGACGAGATACCGGCGGCCCGGCGGGCCTGGCAGGCGGCGCTCGACGCCCCGGACGAGGAGGGTTCCGAGAGCCTGACGGCCCTGCGGGAGCGGCTGGCGGCCCAGGCGCCCGAGGCCCGCGCCGGCACGCTGCTGGCGCTGGTGCGCTCCCATGTGGCGGGTGCGCTGCGCTACCCGGCCGCGGAGTCGGTCGACCCGGACCAGCCCTTCAAGGAGCTGGGTTTCGACTCCCTGGCGGCCGTCGAGTTCAAGAACCGGCTGCGCGGCGCCATCGGCCTGAGCCTGCCCGCCACGCTGGTCTTCGACTATCCGACGCCGACCGCGCTGGCCGGCCATCTGGTCACGCAGGTGCTGCCCGAGGAGCCGGAGGCGGAGCCGGTCGCGGCGCACCTGGACGAGATCGAGGCGGCGCTCGCCGCCCTGGACGCGGACGATCCGCGCCGCTCCGGGCTGACGCACCGGCTGCGGGTGCTGCTGTGGCGATACGACGAGGGGCAGGGCGCCGGGGACGGTGGGCCCGAGCCTGCCGAGGCGACGGGCGGGGACGACCTGGAAGCGGCGTCCGCGGACGAGATGTTCGCCCTGATCGACCGGGAGTTCGGGGAGTCCTGAGCAGTGGCCGAGCCCGTCGCCCGCAGTTTCCCGCGCCGCCGGGGCGCGCCCTGGTGGACAGTTCCGCTTTAGGCGGTTCGCCGATCATCTACGGAAAGGGACCTGTTGCGGGCGAAAGGGAGAGTTTCGTGATGACCGCGCGACAATTCTGAGGAGGAGTCATGCAGAACACCCCGATCAACTTTTCCCGGCAGGGCCGCCCCCGTCCCTTCGACCCGCCCGATGAGCTCAAGCGCATGCGGGAGGAGCGGCCGATCTCGCCCATGCGATTCGCGGACGGCCATTGGGGCTGGCTGGCCACCGGGCACTCGGCGGTGCGGGCCATTCTGGGCGACGCCCGGTTCAGCGCCCGGCAGGAGCTGGACACCCGGACGTTCATCCCCTCGGCCTCCGAGTTCATCTCCGGCATGGGAATCAGCAGTCCCGGCATGCTCCCGCTGTTGGACCCCCCGGAACACACCCGGTACCGGCGTCTTTTGATGGCCGAGTTCTCCACTCGGCGGATGAAACGGCTTGAGACGGCGATCGCCGCGATCACGCACGGACGTCTCGACGCGATGGAGGCTTCCGGCCCGCCGGCGGACCTCATGGCCGAGTTCGCCGCGCCCATTCCGTATCTGATGATCTGTGAACTGCTGGGCATCCCCGAGGAAGGCCGGGAGGAACTCCGGCAGGCGATCGACACCCTGTTCGCCCTGGACACCGAGCCGAAGAAGGCGGAGTCGGCCCTGACCGTCACGCTCAGCTTCTTCCCGCCGCTCATCGAGCGCCGCCGCGCGGAACCCACCGACGACCTCTTCAGCGGTCTGGTCAACGGCGGTCAGCTGACGGAGGGGGAGCTGGCCACCATCGGCCTCCTCCTGTTCGCGAGCAGCCTCCACACCACCGCGAACACGCTGTCGCTGGGCACCTTCGCCCTGCTGTGCCACCCCGAACAGATGGAGGCGCTGCGCCGCGACCCGGGTCTTGTCGACACCGCGGT GGAAGAGCTCCTGCGCTATGCGACGGTCGGCCAGTTCGGTCCCGTGCGCACGGCATTGGAGGATGTCGAGGTCGAGGGGACGATGATCAGGAAGGGTCAGTCGGTGACGGTGTCGCTGCCGACGGCCAACCGTGACCCGGCGCGCTTCGAGGACCCCGACACCCTCGACATCACCAGGCCCGTCGGCGGCCATGTCACCTTCGGCCACGGCTTCCACCAGTGCCTGGGCCAGCACTTGGCCCGCACCGAGCTGCGGCAGGCCTTCCCGGCGCTGCTGAACCGCTTCCCGGGCCTGCGGCTGGCCGTTCCGCCGGAGCAGGTCCCGACCAGGGAAGACCTGTACCTCAACGGTGTCCATCAGCTGCCGGTCGCGTGGTGAGCGGGCGGGCGGCGCCGCGACGGTGACACCGCCCCGGGAGGGCGCGCGGGTTCGGACGCGCGCGCCCTCCCGGGGCGGCCGCGGTCGGCTGACCGACCAGGGGTGTTCAAGGGGGGATCAAGCGGAGCGGTATTCGGCGGCCAGCCGCTCGAGTTCGGGCACCAGCTGGTTGGGCGACGGCTGGGCCAGTACGTCCTGACGGAGCCGTTCGGCGCCGGACCGCAGCGAAGGGTCTTCCAGCATCCGCGCCAGGTATTTCCCGATTTCCTTGCCCGTCGTGCGGTGGGGCGGAAGCCACTGACCTGCCTGGGCCTCTTCGAGGCGCGCGCCGCGCAGCGCGGCGTCCGGGGTGCTGCGGCTGACCATGAGCTGGGGCAGCCCATGCGCCAGCGAGCTGCAGAAGGTGGGAAATCCACCGTGATGGATCACGGCCGAGCAGGACGAGATGATGGCGTGCAGGGGAACGAACTCCACGAGCCTGGTGTTCCGCGGTACGCGCTCCAGCTCCTTCTGGATTCCGGCCGGCAGGGTCAGGACCAGTTCGATGTCCAGGCCGGCCACGGAGTCCAGCATCTTCTGCAGCTGGGCGCTGGAGAGCAGCGGCTTGGTCATGTCCCACATGCTCGTCCCGAATGTGGCGAGCACCCGGGGCGCCTTCCCCTCATGGTGGACCCAGTCGGGCACGAGGGACCGGCCGCTGTAGGGAGCTCGGCCGTTGTACGGCACATAGCGGGTCGAGAGATGGGGCACACCGGTCTCCAGCCTCATGGAATCCGGCCACTGTTCGATGGTGAACTGCCCGGTCAGCAGCTCTTCGGAGAAATCGAAGCCGTATTTCTCCCCCCATCCGCCGAGCCATTCGCGCACGGGGTCCACCCGCTCCCCCGGGTCCTGCCGCGCCATCGTCTTCAGGAAGTGCCGGCGGAGCCGTACGTCCAGTCCGAGGCCGATCGGCATCCGCGCGTGTGCCGCGCCGACCGCCGAGGCGGCGACCGCGCCCGCGTTGGTCAGCCACTCCCAGACGACCAGATCGGGTTTCCACCAGCGGCAGTACGCGACCAGATCGTCGATCATCGCGTCGTTGACGATCCTGGATCTCGCGACGGCACCGGAGCACAGCGCCTTCAGATAGCTCCACGGAAGCAGCTCTTCGCGGTTCTCGCCCAGATCGATGGGGTCGACGATTCCCTTCCCGTCCCCGAACGCCTCCTTCTGCTCTCGGTACGCCCTTTGCAGGATGGGTTCCTTCGATCCCACCGGGACCGCCGTCAGCCCCGCTTCGGTGACATTGACGGCGAATTCCCGGCTGCTCGCGACATGGACCTCGTGGCCGGCCGTGCGCAGCGCCCAGGCCATCGGCACGGTGAACCAGAAATGAGTTCGCCAGGGAAATGCGACGAACAGGACGCGCATGGGCGCCATCCTCTCTCTCATGGGAGGGACCGCCCTTATTGTCGCCGCCTCCACTAAAGCGGATCTTGCGCACCGGCAGCCTCGTTTTCCGGGCCGGCGCTCCATGTCAGTCCGCCTTTAGCGGCGTACGGGAAGCTGCGTACCGGCAGTCACCCGAGCAACATCGACGAGTGGGAGAGCGAGATGGTGCAGGGTTTCCAGGCCAGTCGGCAGTGGGAGCGCATCAGCGAACTCTGGGTCACCGAGGACGCGGCCACCGATCTGACCGGTTTCAAGTCGGATCGGCGGAATTTCAATATCGCGCTCTGGGATCCGACGGCCAATGGGGTCAGGTATTTGAGGGCCCTTGTGTACGAGCTGGCCACGCGGCTGAGCGAAGACGACTGGTCGAAGATCGAGAATGTCCGCAACCGTGAGGTGGGAGACCCCGTCACGGTCCGCTACGAGGGCAGGAGCATCTGTCTGGACTATCTCCAGGCGGCGCTCGAGCTCGGATTCATCGAGAAGGAGCTGGACCTGGGCGGCGCCCGTGTCCTGGAAATCGGCGCGGGGTACGGCCGCACCTGCCACGCGATGCTGTCCAACTACGACCTCGCCTCCTACACCATCATCGATCTGAAGAACACGCTCGCGCTGAGCAGGGCGTATCTGCGCGCCGTCCTGGATGAGAAGCAGTTCGCCAAGATGAAGTTCGTGCAGGTGGAGGACATCGACACCGCGCTGGGCGCGGACCGCTTCGAGCTGTGCGTCAATGTGCACTCCTTCACGGAGATGGCCCCCGACACCGTCGCCGCCTATCTGCGTCTGATCGACGAGAGGTGCGGGGCGTTCTTCGTGAAGAACCCGGTCGGGAAGTTCCGGGACAAGAGCATGGACGGCCACCAGAAGGGCGAGGAGGCCGTGCGGCTGGCCATGGAGAGCGGACCGCTGCGGCAGGTGCTCGACATCCACGACAGCGAGGCCGTGGCGGCGGCCGTGCCCGCCTTCGTCGACGCGTACCGGCCCGGCGACAAATGGACCTGCGCCGCCGATACGCGGGGCCTTCCCTGGAGCTACTTCTGGCAGGCTGTCTTCCGGAAAACAGGCGGCGAGAAGACCGGCAGCGACCTTCCGTAGCCCCGTCCTCCCGGGAGGGAACCATGGCCGCCTCTCCGGCGCCCGCGCTCCGCGCTGACGACGCTCCGGCCGGCACGCCGGTCCTGGTGCTGGGCGGCTCCGGATACCTGGGGCGGCACATCTGCGCGGCGTTCGCCGCCACGGGCGCCCGGGTGTCACGGGTCTGCCGCGGCACGCGCGGTGGCGGCGCGGACGGGGACGGCGCGGACGGGGACGACTGCGGCTCCATACGCCTGGACCTGAGCGCGGCCGGCCCCGCCGAGCTGGCCCGGCTGTGCTCCGACACGCGGGCGCGGGTGGTGGTGAACGCCTCGGGCGCGGTCTGGGGCGGCGGCGAACGGCAGATGACGGAGGCCAACTCCGCGTTCGTGTCCCGGCTCGCCACCGTCGTCGCCGGGCTGCCGGACCGGCCGCGGCTGATCCATCTGGGCAGCGCCTACGAGTACGGCCCGGCCGCGCCCGGGACCTCGATCGGCGAGGACTGGCCGACCGACCCGGCCACCGTGTACGGCCGCACCAAACTGCGCGGCTCGCAGGCCGTGCTGCGGGCCGCGGCCGAGCGCGGCGTGCCCGGGACCGTGCTGCGCATCTCGGTCGCCTGCGGTCCTGGCGCCCCGGGCAACAGCCTCGCCGGGGTCG TGGCCGCCCATCTGGCCTCCGGGCGCGGCGAGTTGCGGCTGGCGCCGCTGCGCGACCACCGGGACCTGGTGGACGTCCGGGACGTGGCCGACGCGGTGGTCGCGGCGGCCGTGGCGCCGGTGCGCGCGGTCGCCGGAACCGTCGTCAACATCGGCAGCGGCCAGGCGGTGCCCGTGCGCCGGCTGGTCGACCTGATGATCTCGCTCAGCGGGCTGCCGGTGCGCGTCGTCGAGGACCCGGCCCTGCAGCGGACGCGCTCCGACGCGGCCTGGCAGCGACTGGACATCGGACGGGCGCGGCGCCTGCTGGGCTGGGCGCCGCGCCGAACCCTGCGCGAGTCACTGCGTGATCTGCTCGCGGCCGCCGGCTCGCCGCCCGCGGCGGCGCGTACGGCGACGGCATGCGGGCCCGGGAACAGCCATGGGAAGGACAGCAGATGAGCGAACGGGTCGCGCGCATCCTCGACGAGGTGCGCAAGTACCACCAGGACACTCAGGAGGGGCGGGGCTTCATCCCCGGGGTCACCGAGATCTGGCCCTCGGGTGCGGTGCTGGACGAGGAGGACCGGGTCGCGCTGGTGTCGGCCGCGCTGGAGATGCGGATCGCGGCGGGCGCGTTATCCCGGAAGTTCGAGTCGGCCTTCGCGCGCAGGATGAAGCGGCGCAAGGCCCATCTGACGAACTCCGGGTCGTCCGCGAACCTCCTGGCGCTCTCCTCGCTCACCTCCCATCTGCTGGGCGACCGCCGGCTGCGCCCCGGCGACGAGGTCATCACGGTGGCGGCGAGCTTCCCGACCACCGTCAACCCGATCCTGCAGAACGGGCTGGTCCCCGTCTATGTGGACGTCGAGCTGGGGACGTACAACGCCACGGCCGAGCGGGTGGCGCAGGCGATCGGGCCGCGCACCCGGGCCATCATGATGGCCCATACGCTGGGCAACCCCTTCGAGGCCGCGGAGCTGGCCCAGCTCGCGCAGGACCACGATCTGGTCCTGATCGAGGACACCTGCGACGCCGTGGGCTCCACCTACGACGGGCAGCTCGCCGGCACCTTCGGCGATCTGACGACCGTCAGCTTCTATCCCGCACACCATCTGACGATGGGCGAGGGCGGCTGCGTGCTGACCTCGAACCTGGCGCTGGCGCGGATCGTGGAGTCGCTGCGGGACTGGGGCCGGGACTGCTGGTGCGAGCCGGGGGAGAGCGATACGTGCCGCAAGCGGTTCGGCTACCAGATGGGCACGCTGCCGGCCGGCTACGACCACAAGTACATCTTCTCCCACATCGGATACAACCTGAAGTCGACGGATCTGCAGGCGGCGCTGGGGCTGGCCCAGCTCGACAAGCTCGACGCATTCTGCTCGGCACGGCGGCACAACTGGCGCCGGCTGCGCGAGGGTCTTGACGGGCTGCCGTGGCTGATCCTGCCGGAGGCGACGCCGCGCTCCGATCCGAGCTGGTTCGGGTTCGTCCTGACCGTCGACCCGCGGGCCCCGTTCAGCCGCGCCGAGCTGGTCGACTTCCTGGAGTCCCGCAAGATCGGCACCCGTCGGCTGTTCGCCGGGAACCTGACCCGTCACCCCGCGCACGCCGAGGCGCCGCACCGGGTGTCCGGCGAGCTGACCAACAGCGACATCATCACCGAGCACACGTTCTGGGTCGGCGTCTACCCTGGGCTGACCGAGGAGATGATCGACTACATGGTCTCGTCCATCACCGAGTTCGTCGGGGACCGCGGCTGAGCGGCGCCACGGCACGCCGATGGCCGCGCGGGCGCCGCGCGGTCATCGGCGTATCGGCTGGGCGGAGTGCTTGAGCGGTTCCCACCAGCCGCGGTTGTCCCGGTACCAGGCGACCGTCTCGGCCAGCCCGGCGGCGAAGTCGTGGCGCGGGCGGTAGCCGAGTTCGGCCCTGGCCTTGTCGTCCCGGATCGCGTAGCGCCGGTCGTGTCCCTTGCGGTCCGCGACGTACCGTACGCGGCCCCAGTCGGCGCCGCAGGCCTCCAGCAGCCGGCCGGTCAGCTCCCGGTTGGTCAGCGCGGTGCCGCCGCCGATGTTGTAGATCTCGCCGGGGCGCCCCTTGGCGCGCACCAGTTCCACGCCGCGGCAGTGGTCCTCCACGTGCAGCCAGTCGCGCACGTTCAGCCCGTCGCCGTACAGCGGCACGTCCTCGCCGTCGAGCAGGTTGGTGATGAACAGCGGGATGATCTTTTCGGGGAACTGGTGGGGACCGTAGTTGTTGCTGCACCGCGTGACGCGCACGTCCAGGCCATGGGTGCGGTGGTAGGCGAGGGCGATCAGGTCCGACGCGGCCTTGGAGGCGGCGTAGGGCGAGTTGGGGTCCAGTACGGCGGTCTCGGGGCTGGAGCCGGTCTCGACGGAGCCGTAGACCTCGTCCGTGGACACGTGGACGAAGCGCTCCACGCGGTGCCGCAGGGCCGCCTGCAGCAGCGTGTGGGTGCCCTGGACGTTGGTGCGCACGAACGCGTCGGCGCCGTCGATGGAGCGGTCGACGTGGGACTCGGCGGCGAAGTGGACCACCTGCCCGGACCGCGCCATCAGGGTGTCGACCAGCTCGGCGTCGCAGATGTCGCCGTGGACGAACGTCAGCTGTGGGTCGGCGAGGTCGAGGTTGCGCCGCGTCCCGGCGTAGGTGAGCTTGTCCAGCACCGTGACATGGGAGACCTCGGGGCCCCACGGGTCACCGTCCCGCGCGAGGAGCCCGCGTACGTAGGTGGAGCCGATGAACCCCGCGGCCCCGGTGACGAGGAGTCTCATATTTCCTCCAGGAACCGCGCGGGCGGCAGGCCCTGCCGGTACGAGCGGGCCCGGTCCATGACGTACTGGCCGTAGGGCGAATTGCTCATCTCCGCGCCGAGCGCATGACAGTCGTCGGGTCCGATGAATCCCATGTACATCGCGATCTCCTCGACACAGCCGAGCCGGGTGCCCTGGTAGTGCTGTACGTCGCGCACCATGCGGCCCGCGTCCAGGAGGGTTTCGTGGGTGCCGGTGTCCAGCCAGGTGACGCCCCGGCCGAGCCACACCAGGTCGGCCCTGCCCTCCTCCAGATAGGCCCGCAGAACGTCGGTGATCTCCAGTTCGCCCCGGGCCGAGGGGACCAGGCGCTTGGCGATGTCGACGACGCTGCCGTCGAAGAAGTACAGGCCGGGAATGGCCAGGTTGGACCGGGGCCGCTCCGGCTTCTCCTCGATGGACAGCAGCTCGCCCCGGTCGTCGATCTCGGCGACGCCGAAGTGCCGGGGATCGGCGACCTCGTGCCCGAACAGCACACATCCGCGCAGCCGCTGGGCGCTCCTGCGGAGCAGCGCGGGCAGGTTCGCGCCGTGGAAGAGGTTGTCGCCCAGGATCAGGGCGCACTCCTCACCGCGAATGTGATCCGCGCCGACCCGGAAGGCGTCGGCGATTCCCCGCGGTTTCTCCTGGGAGGCGTACGAGATGTTCAGCCCCAGATGGCCGCCGTCCCCGAAAAGCCGGCGGAACTGCGGCAATTCGGAGGGGCGGCTGATGATCAGAATGTCCCGG ATACCGGCGAACATGAGGACGGACAGCGGATAGTAGATCATTGGCTTGTCGTAAACCGGAACCAACTGTTTGGACCCCGCCAGGGTGAGCGGTTGCAGCCGTGTTCCGTTCCCGCCCGCGAGAACGATGCCTTTCATCATATGCGACATCGTCACCCACCGGTCTAAAGCATGACTAACCGCGAATGGGCGCCGGCGCGGGCTCGCAAGAACCGCTTTAGAGGTGTCGGGACGATAGCGGGTGAGAGATGCGGCGTGGTCGACGGCGAGGAGATGGCAGCCATGCGGGTCCTGTTCGTCACTTTTCCCGGGCGGAGCCACTTCCAGCTCAATGTGCCGTTGGCCTGGGCACTGCGGACCGCGGGACATGAGGTTCATGTCGCGAGCGCCCCCGAATTCGCCGACGTCGTCACCGGAGCGGGGCTGGCCGCGGTCGCTGTCCAGCCGAGCGCCGAGGACCTGGTGGAATACTGCCGCTGGTGGCGGCCCGATCTGGTGATCGGGGAATCGGCGAGTCAGGCGGGCGCGGTCGCCGCCGCCGCGGTGGGCGCACCGCACGCACGGATGCGACCGGTCTTCGGCGAGGAATACGGCGACCCGCCGGAGGAGCCGCTGACGGGCCGTTTCACCATCGATCAGACACCGGGATCCCTGCGGCCCGAGAGCGGTCCAAGGACCGTGTCCGTGCGCTACGTCCCGTACGACGGCCCTTCCGTCGTACCGGAGTGGTCCCGCCGCGATGCGGAGCTGCCGCGCGTCCTCGCGGCCTTCGGGGTGAGCAAGTGGAACGGGGGCCGGCCCGTTTCCGCCGAGGAGGCCCAGGAGATGCTGGACGCGACGGCCGACCTCGACATCGAGCTGGTGCTGACGCTCCCCGCGGGAATTCGGCGGACGCTCCAGCGCGTGCCCGCGCACGCGAGAATCGTCGACTTCGCACCGCTGCACGTCCTCCTCCCGTCCTGCTCGGCGGTGGTGCACCGCGGGGGTCTCCCGGCCTTCTGCGGCGCGCCGGCGTACGGAGTTCCGCAGCTCATGGTCGGCCCCGGCGGTCCGGAATCCCGGGCCCGGGGCGGGCGTCTTGCGGAGGTCCGGGCCGGGCTGTGGATTCCGCCCGAGGCCATGAGCGGGCCGAGGTTCCGGGAGGATCTGGTCCGGCTGCTGGACGATCCGTCGTTCCGGTCCGGGGCGGAAGGGCTGCGTCAGGAGATGCTGGCTCAGCCGTCCCCCAATGACGTGGTTCCCGAACTGGAGAAGCGGGTGGCCGAGTACGGCTCCCGTTGACGCATCGACGCTGTTTTCCCCGAATTCCCCCGAGGGGTTCGCCGGACCGCCGGCGAACCCCTCTTTTCTTCGGCCCTTCTTCGGGCCCCGCTCAGGACTTTCCGAATTCGGTGGTGATCAGGTCGAAGATCTCCTCCGCCGTGGCCGTCTCCAGATCGTGGTGGGACCCGGCGGCGCCGGCCGTACGGGCCGGGTCTGCCCACTTGTCGGCCAGCAGCCGCAGCCTGGCGGCGATCCGGGCGCGGGCGGCCTCGTCCACGGCGTCCGGCGCGTGGCCGGCGTCCCAGCCGTCGAGTTCCGACATGAGCTGCTGTTCGCCCGAGGCCGCCTCGGCGCCGAGCAGCCCGTGCAGATGACGGGCCAGTTCCTCGGCCGATGGGTAGTCGAACAGGACCGTCGTGGGCAGTCGCAGCCCGGTGCCGGCGTTGAGCCGGTCGCGCAGCTGGACGGCGGTGATCGAGTCGAAGCCCAGCTCCTGGAAGGGCTTGGTGGGCGGGACGGCGTCCGCGTCGTCGTGCCCCAGGGTGCTGGCCGCGTGCGCCTGCACATGGCGTACCAGGATGTGGTGGCGCTCGGCCGGCGGACTGCCGGCGAGCTTCCGCCGGAGCGGGTCCGCCTCCTCCTCCGACGCCCGGGACGGCTCCTCGGTCCGCGCCGTCGCGGCCTCGGGGAGGTCGGACAGGAGGGGGCTGGGGCGCAGCGCGGTGAAGCTCGCCAGGAAGCGGCGCCAGTCGACGGCGGCGATCACGGCGCCGGCCTCCCGGCGCTCGACCGCCTGCTGGAGCGAGGCGACGGCCAGGTCGGGGTCGAGGGGGTGGATACCGCGGCGGCGGAAGAAGTCGATCTCCTCGGCGGAGGTGGCCATGCCCACCGCGCCCCACAGCCCCCAGGCCACGGAGGTGGCGGGCAGGCCGAGGCCGCGGCGGTGTTCGGCCAGGGCGTCCAGGTAGGCGTTGGCGGCGGCGTAGGCAGCCTGCCCGCCGCTGCCCCAGGACGCGGTGACCGAGGAGAACATGATGAACGCCGAGAGGTCCAGGTGCTGGGTCAGCTCGTGCAGGTGCCGGGCCGCGAGCGCCTTCGGGGCGAGCATACGGTCCAGATGCGCGTCGTCCACGTCCGCGATGAGCTCCTGCTCGCTGACGCCGGCGGCGTGGATGACGGTGGACAGCGGGTGCTCGTCGGGGATCGCCTCCAGGACGCAGCGCATGGCCTCGCGGTCGGCGGCGTCGCAGGCGGCGACGGTCACCGTGGCGCCCAGGGCGCGGAGTTCGGCGGCGAGTTCCCCGGCGCCGGGGGCGTCGGGGCCGCGGCGGCTGGTGAGCAGCAGATGGGCCGCCCCGTGTCCGGCCGCCCAGCGGGCCAGCAGCGCGCCGACCCCTCCGGTGCCACCGGTGATCAGCACGCTGCCCCGCGGCTGCCACGGCCGGCGCGCGGTGGAGCGGTCCGAGGTGGCGTGCACGATGCGGCGCGCCAGCACGCCGGTGGTACGGATCGCCGTCTGGTCCTCGCCCCGGCCATGCCCCGGGGCGCCCGACAGCAGGGCCGCCAGCCGGGGCGCGGTCCGCTCGTCGGGGTCGGCGGGCAGGTCCACGAGGCCGCCCCACCGGTCGGGGTGTTCCAGCGCGGCCACGAGGCCGAAGGCCCAGGTCTGCGCCTGGAGCGGATGCGTCAGCGGGTCGTCGTGGCCGGTGGACACCGCGCCCTGGGTCAGGCACCACAGCGGCGCGGTGATCTTCGCGTCGCCGAGTGCCTGGACGGCGGCGACGGTGGCGGCGAGCCCGGCCGGCAGGGCCGGATGTGCGGGGTGCGGGCGCTCGTCGAGGGCGAGCAGGCTGAGCACCCCGGCGAGGGGGGTGTCGGGGCCTTGGGCGGCCAGCCGTTCGGCGAGCGCGTGGCGGCCGGCCGCCACGGGGTCGAGGGGCCATGCCGTGGCGTCGGCGCCGTGCTCGGCCAGGGCCCGGGTCGCGGTCCGCACCGCCGGGTGGTCCTCGTGGCCGGCGGGGACGAGTACCAGCCAGGTGCCGCTCAGCGCGGGCGGCTCGGGCTCGGACAGCGGTGTCCACCGGACCCGGTGGCGCCAGGAGGCCAGCGTGACGCGTTCGCGGTGGCGGCGGCGCCAGGCGGACAGCACGGGCAGGGCGGGCCGCAGCGCCTCGATGTCCCCGGGGGCGGTGGCGTCGCCGTCCGGCTCCAGCACCCGGCCCAGCGCCTCCATGTCGCGGTCCTCGATGGCGTCCCAGAGTTCGGCCTCG ACCGGGTCCCGGGTGTCGTCGCCCAGGGCCGCACGGGCCGGGGGCAGCCAGTACCGCTCGCGGTCGAACGCATAGGTGGGCAGGGACACCGTCGCGGGTGCGGACGGGCCGGCGAACCAGGGCCGCCAGTCGACGGGCGCCCCGGCGGTGAACGCCTGCGCCAGCGCGGTGGCCAGCTGCGCCGGGCCGCCCTCCTGGCGGCGCAGCGTGCCCAGCGCCACCGCGTCGACGGGCGATCCGGCAGTTGCTGACTCGAAGCACTGCTGGAGCGCGGGGACGACCACGGGGTGCGTGCTGACCTCGATGAACAGCCGGTGTCCCGCGGCGAGCAGGGTGTCGACCGCCTCGGTGAGGCGGACGGGCTGCCGCAGGTTGGTCAGCCAGTAGTCCGCGTCCAGGGCGGTGGTGTCCATCAGGCCGCCGGTCACGGTCGAGCAGAACGCGACGTCCGTGGCCGCGCCGCCGACCCCGGCGAGGCGGGCCGTCACCTCGTCGGCGATCTCGTCCACCTGGGGGCCGTGGGAGGCGTAGTCCACGTCGATGGCGCGGGCCCGGGCGCCGGTGGCCTCGCAGGCGGCGACGACGGCGGCCACCGCGTCGGGCGGGCCGGAGACCACGGTGGAGGACGGGCTGTTGAGCGCCGCCACGCCCACGCCCGAGGCTGCCTCGCCGAGGTCGGAGACGATGCGCTCGGCCGCCTCGGGGGCCACGCCGAGGGAGGCCATCGCGCCCCGGCCGGCCAGCGCCCGCAGCGCCCGCGAGCGCAGCGCCACCACCCGGGCGCCCTCCTGGAGGGTGAGCGCGCCCGCGACGCACGCGGCGGCGATCTCGCCCTGGGAGTGTCCGACGACGGCCGCGGGCCGCACGCCGTGGTGGGACCACAGGGCGGCCAGGGAGACCATCAGGGCCCACAGCACCGGCTGGACCACATCGACGCGGCCGAGGTCGGCCGCGCCGTCGGCCCCGCGCAGCACATCCGTCAGGGACCAGTCCACGTACGGGGCGAGCGCCGCCTCGCACTCGGCGATCCGGGCGGCGAACACCGGTGAGGCGCCGAGCAGTTCCGCGCCCATCCCGGGCCACTGGGAGCCCTGCCCGGGGAACACCAGGACCGCTCCCGCGCCCGCCTGGCCCGGTGCTCCGGTCACCACTCCGGGCGCCGGCTCGTCCGCCGCCAGCGCGCCGAGCCGCGCCCGCAGTGTCTCGGTGTCCGGGCCGGTGACGACCGCTCGGTGCTCGAACACCGAGCGCGTGGTCACCAGCGACCAGCCGACGGCCCGCGGATCGGCGTCGAGCGTCGCGTCGAGCAGCCGCCGGGCCTGTGCGCGCAGCGCGGACGCGCTGCGCGCCGACAGCACCCAGGGGGTGACGGGCGCGGGCTCGGACGCGGACGGCGCGGGCTCGGACGCGGACGGCGCGGGCTCGGGTGCCGGAGGCCCGGGCTCGGGGGCCTCTTCCAGGATCAGGTGCGCGTTGGTCCCCGAGAAGCCGAAGGCGGACACCCCCGCCCGCCGGGGCCGCGCGGCGCGCGGCCACTCGACGGCCTCGTCCAGCAGCGCCACCGCGCCGGAGTCCCACGCCACATGCGGGCTCGGCTCCGCGATGTGCAAAGAGCGCGGCAGCGTCTCGTGGCGCAGCGCCATGACCATCTTGATCACACCCGCGGCGCCGGCGGTGATCTGTGTGTGCCCGATGTTGGACTTGATCGACCCCAGCCACAGCGGCCGGCCCTCCGGCCGGTCCTGGCCGTAGGTGGCCAGCAGCGCCTGGGCCTCGATGGGATCGCCGAGGCTGGTGCCGGTCCCGTGGGCCTCCACCGCGTCCACGTCGGCCGCGGAGAGCCGGGCGTTGGCCAGCGCCTGCTGGATGACGCGCTGCTGCGCCGGGCCGTTGGGCGCCGTCAGCCCGTTGCTCGCCCCGTCCTCGTTGACGGCGGAGCCGCGGATGACCGCCAGGACCCGGTGCCCGTTGCGGCGGGCGTCCGACAGCCGCTCCAGCAGGACGATCCCCGCCCCCTCGGCGAGGTTCATGCCGTCGGCGTCCGCCGAGAAGGGCTTGGCGCGTCCGTCGGGGGCCAGGGCGCGCAGTTCGCTGAACCCGACCAGCGGCGCGGGCGAGGACATGATGTAGACGCCGCCGGCCAGCGCCAGCGTCACCTCCCCCTCCCGCAGCGCCTGGCAGGCCAGGTGCATCGACACCAGCGCCGAGGAGCAGGCGGTGTCCAGGGTGACCGCGGCGCCCTCCAGGCCGAGGGCGTACGCGACGCGCCCGGCGACCACGCTCGGGGAGTTGCCGGTGGTCAGATAGCCGGCCGCGTTCTCCGGTACGTGGTAGGAGTTGAGGAAGTAGTCGAGGCCGTCGCAGCCGAGGTAGGTGCCGGTGGCGCTGGAGCGCAGGGTGTGCGGGTCGATGCGGGCGTGTTCGATGGCCTCCCAGGCCACCTCGAGCGCCAGCCGCTGCTGCGGGGCCATGGTGACGGCCTCGTTGGGGCTGATCCCGAAGAACGCGGCGTCGAAGCGGTCGGCGTCGTGGACGAAGCCGCCTTGGCGCACATAGCTGGTGCCCGGATGCCCGGGGTCGGGGTCGTAGAGCCCGTCGAGGTCCCAGCCGCGGCCGGTGGGCAGGCCGCCGGTGCCCTCGCGGCCGGCGGCGACCAGGTCCCACAGGTCCTGGGGGGAGTTCACGTCACCGGGGAACCGACAGCCGATGCCGATGATCGCGACGGGCTCGTGGTGGGCGTACTCGACGTCCTTGAGCCGGCGCTGCGCCTCGCGCAGATCGGCCGTCACGCGCTTGAGGTAGTCGAGGAGCTTCCTGTCGTCGTCTGCCATGTCAGGACCGCTCCAGGGCCGACCGGTCCGCGTTGCGGGCCAGTTCGAGCAGGTCGGCGGCCACCCGCTCGGGCTGGTCCGCGTGGAGGTTGTGGTCGGCGCCGACGTACCAGCGGGAGTCCACGTGTGCGATGGCCGACTCGGCCTCGGTCACCCACTTGCGCACCCAGTCCCCGAGCGCGGAGGCGTACGAGGGCAGGGCTATGAGCATGAGGACGGGCACCGCGATGCCGGGGTACCAGCGGGCGGGCGAGTCGTTCCACATGCTGTTGAGGATCGACAGGCGGTGTTTCAGCGGCAGCCGCTGCACGAGCAGCCCGTCCGGCCCTTCCACCGTGTCGGCGAGCATCGCCTCGACGGCGTCCTTCGACCAGTGCGGGTGGAGCGTTCGTATGCGCTCCCGCGCGGTGTGAACGGTGACTCCCGTGGTGCCGGGGACCCCGTTCGCGATCTTCTCCACGTCCTTCTGCCAGGTGGGGATCCGCAGCGGGGTGTCGGTGTGGTTGATCCACCCTCCGTCCACCAGCGCGAGGCCGGCGGCCAGGTCGGGGTGGACGGAGGCGAACCGCACGGCGACCATCCCGCCCCAGGAGTGGCCGGCGAGCAGTGCGCCCGTCAGCCGCAGCTCGCGGCAGACGGCCGCCAGATCCGCCACGGCGGCCTCGTTGTCGTACCCCTGCTCCGGTACGTCGGAG TCGCCGTGTCCGCGCGTGTCGATCGCGTAGACGGGGTGGCCGGCGTCCGCGAGCCGGCGGGCCACGTCGTCCCACATCCTGGCGTTGGACGCCAGCCCGTGGAGCAGCAGGAACGGCCGGCCGCCGCGCCCCGGCCGGTGCCGCACGTTCAACGTCACTTCGTGGTCAACCGGAACGGACAGCCTCATGACGGGGTTCCCCTGGCTCCTGGGAGTTGGGACGAGATGGTGATCGGCCGGGCGGGTCGCGGCGCCGGCGCCTAGGCGGCGTCGGCCGCGTAGGCCTCGGCGAGGTACTTGCCGAGCAGGGTGGAGGTGGGGTGTTCGACGATGGACACGAGGGGGACCTCGATCCCGGTGTCGTCCATCAGGAACTTCGAGAGCTTCACGGCGGTGAGCGAGCTCAGGCCGTTCTCCAGGAAGTTGCTCTCCTCGTCGAGCGACGGTACGTCGAGGATCTCGGCGGCCCGGCGGAGCACCAGCTCGCACAGCAGCTGCTGGCGTTCCTCCGGCGCCGCCGACGCGAGCCGATCGGCCAGCTGACCGTCGTCGGGGGATCCGTTGGTGGGTTCCATGGGTGCACCCTTCTCGGTGTGGTGTCGGGCTGACGGGTGTGTGCGGTGGGCTAGACGGTGGGCCGGCCGAGTACGCCTCTTGGGGCCGTGCCGGACGGCTTGAGCCCGACCATCTCCAGCTCCTCGGGCCGGAACGGCGGTTCCACGAGCTCCGGGTAGCTGGTGTCGGACTGCAGCAGCGACAGGAAGCGGGCGTCGCCCAGGGCCTTCTGCGGCGCGTTCAGGCTCAGCACGCCGGTGGCGACCTCGCAGACCTTCGGCGACCTGATCGACTTGCTGGAGATGTAGTCGGAGAACCTCAGCCGCTCCGCGGTGTCCGGGCCGGTCAGCCGCGGGTCGCGGGACAGGTTGCGGCAGTTGACGAACTGGATGTCGTTCAGCCCCGCCATGATCCACGGGTCGTCGACCACCTCGCTCAGGGCCCGCTGGATCTGCCGGCCGCGGTTCTCGCCGAACCCCTCGCGCGCCAGTTCCCGGTCCAGGGCCTCGGCGGCGCGGGCGGCCGAGCTCATGCCGTGTCCGTAGACCGGGTTGAACGCCGCCAGGGAGTCGCCGAGGATCAGCAGGCCCTCCGGCCACTGCGCCATGCGCTCGGGGTACAGCCGGCGGTTGGCCCCCGAGTGCGACTGGAAGATCTGGCTGATGGGTTCGGCGACGCCGATGAGGTCGCTGACGATCGGGTGCCGCAGCTCCTTGGCGTAGGCCGCGAACTCGTCCTCGCCGCCGGGCAGCGGAGCGCCGCGCGTGCTGGTCAGGGTGACCAGCCAGCGTCCGCCCTCCTGGGGGTAGACCACGCCGAAGCGGCCGGGCTGCCGGGTGAGCGGGTCGGCGGCGACCTGGATCGCGGGGAAGGCGCTGCCCGCGCCCTCGGGCGCCTTGAACATCCGGGTCGCGTACCCGATGCCGGCGTCGACCACGTCCTGCTCGACGGTCGGCAGGCCGAGGGCGGCCAGCCAGCGGCCCAGGCGCGAGGCCCGCCCGGTGGCGTCCACCACCAGGTCCGCCTCGATCAGCCTGGGTTCGCCACCGTCCGCGTCGCGCACCCGCACCCCGGTGACCCGGGAGCGGTCGCCGGCCAGGTCGACGGCCTCGGTGCCCTGCTCCACCCGGACCCGGCCGTCGGCGAGGATCGCCTCGCGCACCGTCCAGTCGAGCAGCGGGCGGGTGCACATCATCGCGTACGCGGTGGCCGGGAAGCGGTACTGCCAGCCCGCCGAGGTCAGGGTCACCAGGTCGCTGTGGAAGCCGATCCGGCGCGCACCGGCGGCCAGCAGCCGGTCGGTGGTGCCCGGCAGCAGGTTCTCGACGATGCCCGCGCCGCTGGACCACAGCACGTGGACATGGCGGGCCTGTGGCTGTCCCTTACGGTGGTGCGGCCCGTCGGGCAGGATGTCACGCTCCACCACGGTCACGGTTGCCAGGTGACGGGACAGCACATGGGCGGCCAGCATGCCGGCCCATCCGCCGCCCAGCACAACGGCGCGTGTCGGTGTGGTCATGGAATCAAGTCCCTTCGCAACGGGCTCGTCCGCGCGGGTGTCTCTCTGCGGCCTGCCAGGCCCATCACGAGGGTGTCCTGAACAGCTTAAGCGGGCCTTTCGGCTCCGGCGGGTCCGTGGCGCGGGGCGCGGGGCCGGCGCCCGTCCCGGGCTCGGAGTGCCCCAACGTGGTGTCCGTGAGGCCCCAGAACCCGCGGATGTGAACGCCCAGGCCGTCCTCGTCCAGTTCGCAGATGGTGATCATGCGCATGCGTATCTCGGCCGGTACAAACACCCGCGCGTCTCCGCGGATCACCACGAACCGTCCGTCCATCGACGACACGGGCCGCCCCAGCACCTCGTGCACCTTGCCCTCCGAGCCCCGGAACACGTGCTCGCGCAGGGCGTCCTTGCCGCGCAGCAGCAGGCCGCCCACCGGGTCCTCGAAGACGATGTCCTCCGCGAACATGGCGACGGTGCCTTCGATGTCCCCCTTCGCCAGCAGTCCGAGGTAGGTGCTCGGCAACCGCCTGAGGGCCGCCTCCTTCGGCGCGATGACGTCGGGGCCGCGGAACGTCCCGGGCGCGCCCGCCGCCGAGACCTCGAGGTCGGGCCGGCCCCAGTACGCCCGCATGTCCTCGATGAGTCCGGACTCGCCGACGCGGAGCAGCAGCGCGTAGTGGCAGCGCAGGCCGGCCGGTTCCGCGCCCTGGGGCGGGGGCAACCAGCCGCGGTCCGCGTACACCGGGCCGCGGGGCCGGTAGTCCATGTCGGCGGTGATCCTGGACAGGACGTGTGTGCCGTCCTGACCGACGACCGTGTCCTCCACGGTCTCCCGTACGTTTCCGGCGACGGCGCTTCGGAAGTGTGCGCGCAGCGCCTCGTGTCCCCTCAGGCCACCGGTCCCGACGGGGTCCTCGAACGTGGCGTCCGGCGCGTACAGGCCGATCAGCGCGTCGATGTCGCCGGCGCCGAGGAGCCGGCTGTGTTCGAGTGCGATCTTCTTGCGGGTGCGCTCGTTGAGCACCGTGTCCTCCCTGGCCTTAAGGACCTCGGCCAGTCACCCTTGCCGAACGGCCTTAAGCAGCCCTTTCCGCCGGTGCGCGGGCGGGCGGGGCCCGCCCGGGCGACAGGCCTGCTTTAGGCGGATCGGCGATCCTCCGCTGAGACCGGTGCGGATGGCCGACGACGGAAGGCCCGAAGATGACACCAACGAAGACCGAGCAGGTCATCATCGACAACGGCGGCAACTCGGTGGTGAACGGGTTCCGGTCCGCCGCGCGCTTCGTGCAGTGGATGACCGCCTCCCCCACCTCCCGCGTCAGCGCGCTGTACGAGCTCAACAGCCGCAGGCTCACCGGACGCAGCGCCTACCGCGGCTTCCTGAATGTGACGCGCAGCCAGGTCGAGATCGGGCGGCGGCGCGCCGCGGAGAAGAACCTGAGCGGCCGGGTGGACCTGCGCCTGGGCTCGGCGACGGACGTCCCC TTCGAGGCAGGTTCCTTCGACCGGGTGGTCGCCCTGGAGTCCGCGTGTCATTTCGACACCCGTCAGAAGTTCTTCGAGGAGGCGTTCCGGGTGCTGCGGCCCGGCGGTGTGCTCGCCACGGCCGACCTGGTGCCGCGCCCCGCGCCCCGCAGGAAGACCCTGGCGGCCCGCTTGGAGCGGTTCGGGTATGAAGGCCTACATCAAAACGATCACCGGGCAGGCGGTACGCCTGGAGCACATCATCGCGGCGGCGCGGAAGCCCGGTGAGGCGTGATGCCCACAGGCGAGACGCCGAAGACGCCGGTGCGGTGCCCGGTCTCGGTCAACGACCCGGAGCTGACCGCCGACCCCTACCGCGGCTTCAGCCGCATCCGGGAGGAGGCGCCGGTCACCCTGGGCACCCTGGCCGACGGCCGGAACATCTGGGTCGTCACCCGCTACGACGACGTCACGGGCGTGCTGACCGACAGCCGCTTCGTCAGCAACTCCCGGTCGGTGCCCGGCTCCACCACGGACCGCCACGCCGCGTCGCTGACCTGGCTCGGCCTGCCCGAGGAGCTGATTCCCTATCTCTCCCGCGCCATCACACAGCTCGACCCGCCCGACCACACCCGGCTGCGCAAGCTCGTCACCCGGGTGTTCTCGGCGCACCGGGTCGCCGCTCTGCGGCCGCGGATCCGGACGCTGACGCGGGAGCTCGTGGACGCGCTGCCGGGACACGCGGTGGACGGCACGGTCGACCTGGTCGAACACTTCGCCCAGCCCCTGCCCGTCACGATCATCTGTGAGCTGATCGGCGTGCCGGCCTGTGACCGGGCGATGTGGCTGCGGTGGAGCCACGACTACAGCGACGCCCTGCGGCTGAAGAACACGCTCATCCAGGCCACGGCCTATCTGCGGGAGCTGGTCGCCAAGCGCCGGGTAGAACCGGCGGACGACCTGCTCACGGCGCTCATCCAGGCCCGTGGCGAGGACGGCGAGGGCCTTTCGGAGACCGAGGTGGTCACGATGGCCTTCCACCTCGTGGTCTCCGGCCACGGAACCACCTCCGGCGTCATCGGCAACAGCGTCCTCGCCCTGCTGACCCACCCCGATCAGCTCGCCCTCCTCCGGAGCGATCCGGAGCTGATCCCGGGAGCCGTCCAGGAGCTGCTGCGCTGGCGCAGCTCGGTCGTCTTCGGCAAGGCGCGGTACGCCACGGAGGACGTCCGGGTCGCGGACACGCTGATCAGCCGGGGCGATGTCGTCCTGCCGGTGCAGGGCGCCGCCAACCACGATCCGCGGCACTTCCCCGACCCTGAGCGGCTGGACATCACCCGCCGCCCCGACGGCACGGGGGTGCAGCACGTCGCCTACTCGCGCGGGCCGCACTACTGCCTCGGCGCCATGCTCGCCAACCAGGAGGTGGAGCTGGCGCTGGAGACGCTCTTCGGCCGCTTCCCCGGGCTGGCGCTCGCCGTGCCCGAGAAGGAGCTGACGTGGCGCCCCGTCCCCGGGACCCGGCAGCTCGACCGGCTCCCCGCGGTGTTGGGCGCCGGCGCCTCCGAGGCCGCCTCTCGGTGACCCGGTATCCCGGGGCGCACACCGAGGCGACGCCACGAGGGGCCTCGCCCGTACGGGCGCGGCCCCTCGTGGCACCGCCTCGGTTCAGCGCCGGCCGGGCAGCTCCTCGGGGTGCCGGCTCCGCAGCGTGTCGAACGCCGCGCTCCAGTACCGGGCGCGCTGGAAGGCGTACGTGGGCAGCTCGACGCGCCGGGCGTCGGTCCCGGCGAACACCGCGTCCCAGTCCACCGCGGTGCCCTGCGCGTACACCCGGGCGAGGGCGGTGGCCACCGCGGTCGTCTCGGCCACGCCGGGCCGCAGCGCGGCCACCGCGTGCTGCCCCGCGCCGTCGAGGAGTTCGGCCACCTCGTGGCCGCCCAGTTCGAGGTGGACCGTTCCGTCCTTGGCGACGGCGCGGGCCTGGTCGGCGATGTCCCTCGGCGTCTGCCCCGGGTCGTGCGGTCCGGTCAGCGCCGCGCAGGCGTCGGGCAGTGCCAGCCGTCCGCCGATATGTTCCTCGGTGATGTGGCCGATGCCGTGGCCGTGTACGGCGCCGGGCCGCACGCCCCACGACTCGGCCAGGCGGAACAGCGCCACCTGGACCGCGAAGGCCCTGGCCGCTTCGAGGCCCGCGGCCGGGGCGGGGGCCGCGCCGGTGAGCATCGCGTCACGGGCGGGGAACCCCAGGTGGGCGTCGAGCGCCGCGCAGACCGTGTCGAACGCGCCGGCGAAAGCCGGGAAGGCGTCGTAGAGCTGCTTGCCGGTGCCGGGGGCGAGGGCGTGGCCGGTGAGCAGGACGACGAGCCGGTGGCGGCGGCCGGGCACCCCGTGGACCACGTGGGGCGCGGGTGTCGCGTCGGCCAGCGCCCGCAGGCCGTCCAGCAGGTCCTGGCGGCTCTCGCCGACCACCACGCCACGGTGTCCGAGCGCGGCCCGGGACGTCGCCAGCGACAGGCCGACGTCCGCCGGCCGGAGACCGGGCCGCCGCTCGACATGGGCGAGCAGCCGGGCCGCCTGCGCGCGCAGCGCGTCCGGGTCGCAGCCGGAGACCGGCCAGAGCACCACGCCGCCGCCCGCCGCCTCGGGGGCCGGGGGCGGGGGTTCGTCGTCGGGGGCCTGCTCCAGGATCACATGGGCGTCCGTACCGCCGAAGCCGAACGCGGACACCCCGGCCCGCCGTGGCCGGTCCGTCCCGGGCCACGGTGTGGCGTCGGTGACCAGCCGTATCCGGCCCTCGTCCCAGGGGATGTGCGGGGACGGCGCCTCGGTGTGCAGGGTGCGCGGCACGATGCCGTGGCGCATGGCCTGCACCATCTTGAGCACTCCGGCGATACCGCTGGCCCCCTGCGTATGGCCGAGGTTGGACTTCACCGCGCCCAGCAGCAGCGGCCGGTCGGCGGGGCGACCCTCGCCGTAGACGGCTGCCAGGGCCTGCGCCTCGACCGCGTCGCTGAGCAGTCCGCCGGTGCCCTGGCCCTCGACCGCGTCGACCTCGTGCGGCGCCAGCCCGGAGGCGTCCAGCGCCCTTCTGATCAGCCGCCGTTGGGCGGAACCGTTCGACGCGCTCGCGCCGTTGGTGGCGCCTTCCTGGCCGATCGCGCTGCCGCGGACGACGGCGAACACGGGGTGTCCGTGGGCGCGGGCGGCGGACAGGCGCTCCAGGAGCAGCACCCCGGCCCCCTCGGCGAAGCCGATCCCGTCGGCCCCGTCGGCGAACGAGCGGCAGCGGGCGGCGACAGGCAGCCCTATCCCCCGGGCCGACCCGATGAACGTGTCCGGGCCGCACATCACGGTGACACCGCCGGCCAGCGCCATGGAACACTCGCCGCCGCGCAGCGACTGGCAGGCCAGGTGGAGCGCCACCAGGGAGCCGGAACACGCGGTGTCGAGGGTGGCCGTGGGCCCTTCGAGGCCAAAAGTCAGGGCGATACGGCCGGAGAGCACGGCGCTGGAGCCGCCGGAGGCGACGTGGCCGAGCAGTTCCTCGGG GACGTTCCTCAGGTGCGGGGTGTAGTCCTGGCCGGTGGTGCCCATGAACACGCCGTAGCGCCGGCCGGCGACCGACCGCGGGTCGATCCCGGCCCGTTCGAACGCCTCCCACGAGGTCTCCAGCAGCAGCCGCTGCTGGGGATCCATCACCGACGCCTCGCCCGGGGAGATCCCGAAGGGCGCGGGGTCGAACGCGGCGGCGCCGCCGAGGAATCCGCCCTCGGACACCGCGCTGCGCGCCTGCGGGTGGGCGTCGGGCCCGCACATGCCGTCCAGGTCCCAGCCGCGGTCCCGGGGGAAGGGGCAGATGGCGTCGCGCTCCTCGGCCAGCAGGGTCCACAGGTCGTCCGGGGATTCGACACCGCCGGGGTAGCGGCAGGCCATGCCGACGATCGCGATCGGCTCCCGGGGGGCCGCGCGCAGCCGCTGGTTCTCCTTGCGCAGCCGCTCGGCCTCCTGCAGCGAGGCGCGCAGGGCTTCGACGATCTTGTCGTCGGCCACGGTCATGACATTCCTCCGACGGGACGGCACAGGGGGCGGCGGACAGGACGGCACACGTCAGGACTCGCCGTTGCGCAGGGCCATGTCCACCAGTTCGTCGAGGTCCATGGAGGCGATGTCGGCGGTGTCGGCGTCGCTTTCGTACGGGGCCGGGGCCGGCTCGGACACGGTGGCGTCCGCCTCCGCGTCCGTCTCCGTGTCCCCGCCCTCGCCCAGCCGCAGCAGCGCCTCCAGCAGTCCCGACTGCTCAAGACGCCGCAGCGGGATGGCGGCCAGCACCTGGCGGACCCGGCTCTCGAAGGGGTCGGTGGGCGGGGCGATCTGCTCGCGCAGGTGCTGGGCGAGCGCCAGCGGGTTGGCGAAGTCGAAGACGAGCGTGGCGGGCAGCCGCAGGCCGGTCGCGGCCGAGAGCCGGTTGCGCAGTTCGACGGCGGTGAGCGAGTCGAAGCCCAGCTCCTTGAACGTACGGTCGTGGGCGATCTCGTCGGCCGAGCCGTGGCCGAGTACGGCCGCCATGTGCACGCACACCGCCTCCAGTACACAGCCCTCGCGGTCCGCCTCCGGCAGCGCGGCGAGCCGTTCGGCCAGCGACGGGCCCGAGGTGTTCGCGGTGCCGCTGTCCGCCACCCGCCGCGCCCTGCTACGGCCGGCGGCCGCACCGCCGGCGGGGCCCTGCGCGGACTGCCGGATCGGGACCAGCAGCGCGTCGCCCGCCGCCTGTGAGCGGTCGAACAGCGCGAGGGCCCGCTCGGTGGGCAGCGGCTCCATACCGGCCTGCCGTATCCGCTGCAGGGCGCCGTCGCCCAGCTCACCGGTGAGGGTGCTGGTCTCCTCCCACATGCCCCAGGCCAGGGACTGGGCGGGCAGCCCGGCTGCCTGGCGGTGCTGGGCCAGAGCGTCCAGGAAGGTGCTGGCGGCCGCGTAGTTGGCCTGCGAGGGGTTGCCGTACACCCCGACGACGGAGGAGAAGAGGACGAACATCGCCAGGTCGGCGTCCTTGGTGAGCTCGTGCAGATGCAGTGCGGCATCCGCCTTCGGCCGCAGGACCCGGGCCAGTTGCCCGGGGGTCAGGGCGTCGACCATGCCGTCGTCGAGGACGCCGGCGCAGTGCACCACCCCGGTCAGGGGGTGTGCGTCGGGGATGCCGGCCAGTGCCTCGGCGAGCTGCGCGCGGTCGCCGACGTCGCAGGCCTCGACGGTCACGGTGGCGCCCAGCTCGGCGAGTTCGTCGCACAGGTCGGTGGCGCCGGGGGCCTGCGGGCCGCGGCGGCTGGTCAGCAGCAGCCGCCGTACGCCGTGGCGGGTGACCAGGTGGCGGGCGACCAGGCCGCCCAGGGTGCCGGTGCCGCCGGTGACCAGGACCGTGCCGTCCGGGTCGAGGGTCCGCGGCAGGGTCAGTACGACCTTCCCGACGTGGGCGGCGCGGCTGATGAGGCGGAAGGCGTCGCGCGCCCGCCGGATGTCATAGGCGCGCACCGGTGGATGGGCCAGCTCGTCGCGTTCGAACTGGCCGAGGATGTCGCTCAGCATGCGGCCGATGCCGTCCTCCCCCGGTTGCCCCAGGTCGAGGACGCGGTAGTGGACACCGGGGTGGACCGCGGCGAGCTGCCCGGGGTCGCGGACGTCGGTCAGGCCCAGCTCCACGAACCGGCCGTCCTTGGCCAGCAGGCGCAGCGAGGCGTCGGTGGCGGCGCCGGTGAGGCTGTTGAGGACCACGTCGACGCCGCGGCCGCCGGTGGCGGCGCGGAAGGCTTCCTCGAAGTCGAGGTCGCGGGAGGAGGCGCGGTGGGCCTCGTCGATGCCCATGGCCTCCAGTACGGCGTGTTTGCCGGGGCTGGCCGTGGCGTACACCTCGGCGCCCAGGTGGCGGGCGATCTGCACGGCGGCCATGCCCACCCCGCCGGCCGCCGCGTGGATGAGCACCGACTCGCCCGCCGTGAGGCCCGCGAGGTCCACCAGCCCGTACCAGGCGGTGACGAACGCGATGGGCACGGCCGCCGCCTGCTCGTCGGTCCAGCCCGGCGGGATCGGCACGACGGAGCGGGCGTCGGCCACGGCGGTCGCCCCGAAAGCGCCCTGGAACATGCCCATCACGCGGTCACCGACGGACACCGACGTCACGTCGTCGGCCACCTCGACCACCACGCCCGCGCCCTCGCTGCCCCGGAGGCCCGCCTCGCCCGGGTACATGCCGAGTGCGATCAGTACGTCCCGGAAGTTGACGCCCGCGGCACGGACCTGGACGCGGAGGTGGCCGGGGGCGAGCGGTTGGGGTTCGTCCGCCGCCACCAGGTCCAGGTTGTCCAGGGTGGCGGGGCCGGTGATGTCGAGCCGCCAGTGGGGGGTTTCCGGGAGGGTCAGGGCGCCGCCGGACGCGGCGGGGACCAGGCGGGACACCCGGACCGTCCCGTCCCGGACGACGATCTGCTTCTCCCCCGCGGCCACCGCGGCGGCGACGGCCTCCGGCAGCTCGTGTCCGGCCCCGTCCGCATCCACGTCCAGCAGGACCAGCCGGTCGGGGTGTTCGGACTGCGCGGAGCGGATCAGGCCCCACACCGGGGCGTGCACGAGGTCGGTGACGTCCTCGCCGTCGGTGGCGGCGACCGCGCCACGGGTGACCACTGCCAGCCGCACCCCGGCGAACCGCTCGTCGGCCAGCCACCGCTGCACGGTGTGCAGCACCTCGCCCAGCCGGCGCCGCACGGCCTCGGCCAGGTCCGGGTCGTGCGGCGCCGGATCGCAGGGCAGCACGATCACCGGCGGGAGGGGCAGACCGCCGTCCACCGCGGTGGCGAGCGCGTCGAAGTCGCCGTGGCGGCGCGCCCCGTAGCGGCTGTGCGAGGTGCCGGCGGCGACCGCGGCCCAGTCGTCGGTGGAGACGCGCGGGTCGGGCCCGGCGTCGGTCACAGGGACGTAGGCCACGCGGAAGAGTGCGTCGCGGGTGTCCTCCGCGGCGCCGCTGGGGAGTTGCCCGGCCGTGAACGGCCGGGTGACCAGGGACTCGATCGAGATCACCGGATGTCCC AAGGCGTCGGTGGCGTGGACGGACATGCCGTCGTCGCCGACCGGTGCGAGCCTCACGCGCAGCAACTCGGCGCCGGAGGCGGCCAGCGACACGCCGTTCCAGGCGAACGGCAGCGCCATCCGGCCCGCGGTGTCGCCGCGCACCGCGGTCAGCCCGCTGGCGTGCAGCGCGGCGTCCAGAAGAGCGGGGTGGATGCCGAACGCGGCGGCCTGCCCGCGCTGGTCCTCCGCCAGGACCACCTCGGCGAAGACCTCGCTCTCGCGCCGGTAGACGGCGCGCAGGCCGCGGAAGGCGGGCCCGTAGCGGTAGCCGCCCTCGGCGAGCTGGTCGTAGCAGCCGTCCACGGACACGGGCTCGGCGCCCTCCGGCGGCCACTGGGCGAGGTCGAACGGCTCGGCGGCCCCGCCGGTCGCCAGCGTGCCGCTGACGTGGCGCACCCACGGCTGGTCGGTCCCGGCCGGGCGGGCGTACGCGCTCAAGGGACGGCGGCCGTTCTCGTCGGCCCCGCCCACCACGAGCTGGAGGTCGGTGCCGCCCTCGTCGGCGAGCACCAGTGGGCTGGCCAGCACCATTTCCTCGACACGGTCGCAGCCCACCTCGTCGCCGGCCCGCACGGCCAGCTCCACGAACACGGCTCCGGGCACCAGCACCGCGCCGGCCACCGCGTGGTCGGCCAGCCACGGATGGGTGTCCAGGCCGAGCCGGCCGGTCAGCACCACCTCGTCGCCCTCGGCGAGGACGGTGACGGCGCCCAGCAGCGGATGGTCGGCGGGGGCGAGACCGAGGCGGGTGGGGTCGCCGGTCCCGGTGCCGCCGGCGTCCAGCCAGTAACGCCGGCGCTGGAACGCGTACGTGGGCAGGTCGAGGGGGATGGTCGGGTCCGGGAACACCCGGCTCCAGTCCACCGCGACACCGTGGACATGGGCCTGGGCCAGCGCGAGGAGGAAGCGGTCCCAGCCGCCCTCGTCGCGGCGCAGGGTGCCGAGCGCCGTGGCGGCCACACCTGCTTCGTCGATGGTCTCCTGGGTGCCGATGGCCAGGACCGGGTGCGGGCTGCACTCGATGAACGCACTGTGCCCGTCCTCGAGCAGCGCCTCGGTGGCCTGCTGAAACCGCACCTGCTGACGGAGGTTGGTGAACCAGTACGCGGCGTCCATGGCGGTGCCGTCGATGCGCCGCCCGGTGACGGTCGAGTACAGCGGGACGGAGCCCGCCTTCGGCTCGATGTCCGCGATGGCCTCGGCCAGCCGGTCGCGCAGCGCGTCGACGTGGGCGCAGTGCGAGGCATAGTCCACCGGGACGCGGCGGGCGCGCACCCCGTCGGCCTCGTAGCCCTCCAGGAGTTCGGTCAGGGCGTCGGCGTCGCCGGAGACCACGGTCGAGGAGGGGCCGTTGACGGCGGCCACGCTCAGCCGGCCGTCCCAGCGCTCCAGGTGTTTCCCGACCTGCTGGACGGGCTGGGGCACGGAGGCCATGCCGCCACGGCCGGACAGCTCGGGCAGCGCCTGGGAGCGCAGCACCACGACGCGGGCCGCGTCCTCCACCGACAGCACGCCCGCCACGCAGGCCGCCGCGATCTCGCCCTGGGAGTGGCCGACCACGGCTGCGGGCTCCACACCGTACGAACGCCACAGCTCGGCCAGGGCCACCATGACCACCCACAGCACGGGCTGGACCACGTCGACCCGCTCCAGGGAGGGGGCGTCCGGCTCGCCCCGCAGCACCGACTCCACGGTGTAGTCGGTGTGCCGCTCCACCGCGGCCGCGCAGCGGCGGAAGTGTTCGGCGAACACCGGGGAGGCGTCGGCCAGGGCGAGGGCCATGCCGAGCCACTGCGAGCCCTGGCCGGGGAAGACGAACACCGTCGCGCCGGGGCTCGGCACACCGGTGACCACCTGGCCGGAGGGGGTGCCCTCGGCGAGCGAGGCCAGCCCGGCCAGGAGGGCGTCGCGGTCGGTGGCGACCACGGCGGCGCGGTGCGACTGGGCGGCGCGCGCATGGGCGAGGGTGAAACCGACACGGGTCGGGGTCGCCTCCGGCCGCTCGGCGAGGAAGTCCCGCAGCCGGGCGGCCTGGGCGCGCAGCGCCGCCTCGCCACGCCCGGACACCAGCCAGGGGACGACCGGCAACTCTGCGGCTGGGGCGGGCTCATCGGCGGGCGGGGCCTGTTCGAGGATGACGTGCGTGTTGGTGCCGCTCATGCCGAACGACGACACACCGGCGCGGCGCGGGGCGCCGGTCTCGGGCCACGGCCGCGCCTCGGTCAGCACCTTCACGGTGCCCTCGGACCAGTCCACCTGGGTGGTGGGCTCGTCCACGTGCAGGGTGCGCGGCAGCAGGCCGTGGCGCAGGGCGTACACCATCTTGATCACCCCGGCCATGCCGGCGGCGGCCTGGGTGTGCCCGATGTTGGACTTGACCGAGCCCAGCCACAGCGGGCTGCCCTCGGCGCGCCTCCTGCCGTAGGCGGCGATCAGCGCCTGCGCCTCGATGGGGTCGCCCAGCGAGGTGCCGGTGCCGTGCCCCTCCACCACGTCGATGTCCCGGGCGGACAGCTGGGCGTCGGCCAGCGCGGCGCGGATGACGCGCTCCTGGGCGGGGCCGTGGGGCGCGGTCAGGCCGTTGGAGGCGCCGTCCTGGTTGATCGCGGAGCCGCGGATCACGGCCAGCACCGGATGGCCGAGTCGTTCGGCGTCCGCCAGCCGCTCCACCAGCAGCACACCCACGCCCTCGGCGGGCCCGAAGCCGTCGGCCGCCGCCGAGTACGCCTTGCACCGGCCGTCGCCTGCGAGCCCCTTCAACTTGCTGAACTCCAGGAACGTGCCGGGCGTGGCCATCACGCACACCCCGCCGGCCAGCGCCAGGGAGGACTCGCCCTTGCGCAGCGACTGCACCGCCAGGTGCAGCGCCACCCCGGACGAGGAGCAGGCGGTGTCCACCGTGAAGGAGGGGCCCTCCAGGCCGAGGGTGTACGAGATACGGCCCGACATCGAGCTCGCGGCCAGCCCGGTGGCCATGTACCCGGCGACGTCCTGCGGCGCGTCGGCGCCGCTGCCGGCGTAGTAGATGGTGCTGCCGCCGACGAAGACACCGGTCTTGCTGCCGCGCAGGGAGGTCGCGTCGATACGGGCGCGCTCGATGGCCTCCCAGGCGGTCTCCAGCAGCAGCCGCTGCTGCGGGTCCATCGCCAGGGCCTCGCGCGGCGAGATGTCGAAGAAGTCGGCGTCGAAGTCGGCGATGTCCCGGACGAATCCGCCCTCGCGCACATAGCTGGTGCCCGTCTCGCCCGAGTCGTTGAACAGGCCGGGGTCCCAGCCCCGGTCGTCCGGCATGGACGAGATCACATCGCGCCCGGTGGACACCAGCTCCCACAGGGCCTCCGGGGTGTCCGTCCCGCCGGGGAACCGGCAGGCCATACCGACGATCGCGATCGGCTGGCGGTCCCGGGCCTCCACCTCGCGGAGGCGCTGCTGAGTGTCATGCAGATCGGTCGCCACTCGCTTGAGGTAGTCGACCAGCTGTTC CTGGTTCGCCATGGCGGTCCTCTTTCAGGCCCTTCCCAGCTGGGAGTCAATGAATTGCAGCACTTCATCGGCCGAGGCCGCCTGGAGCCGTTCCGCGACGCCGTTGCCCTCCGCCGCCGCGGGCTGCTGGCGGCACCGCGCCAGCAGCGCTTCGAGCCGGGCCGTCACGGCGTCCCGCTCCTCGTCGCCGGCGAGCAGATCGACGTGGTCCTCCAGCCGGTCCAGTTCCTGGATCAGGGCCTCCGACCCGCTCGGCCCCTCGGAGACGAGCTGGTCCCGCAGGTGCTCGGCGAGCAGCGCCGGGGTGGGGATGTCGAAGATGAGCGTGGAGGGCAGCTTGATGTCGGTGGCCTGGCTGAGCCGGTTGCGCAGCTCGACCGCGGTCAGCGAGTCGAAACCGATCTCCTTGAAGGGCCGCGCCGGGTCGACCGCGAGTACGTCGCCGATCCCGAGCACGGCCGCCACGTTGCGGCGCACCAGCTCCAGCAGCGTACGGCTCTGCTCGACCGCCGAGAGGCCCGCCAGGCGCTCCGCCATCGACGCGGCGTCCCAGCCGGCGGGTTGCCCCGCGGCCGCGCGGCGAACCGGTGCCCCCCGCACCAGGCCGCTGAGGATACGGGGCAGGACGTTGGCGCCCGCCAGGTCCCGTAGCGCCGCCGCGTCGAGGCGGACGGGCACCAGCAGGCTCTCGGGCCGCCGCACGGCCGCGTCGAACAGTGCCAGGCCCTGGTCGGAGGACATCGCCCGGATACCGGAACGCTCCATCCGGGCGATGTCGCGCTCGGCCAGGGCGCCGGTGATGCCGCTGCTCTGCTCCCAGTGGCCCCAGGAGAGCGACTGGCCGGGGAGCCCGGCGGCCCCGCGGTCCTGGGCGAGCGCGTCGAGGAAGGCGTTCGACGCCGCGTAGTTGCCCTGGCCCGCGACACCGGCCACGCCGCCGGTCGAGGAGAACAGCACGAACGCGGCGAGGTCCGCCTCACGGGTCAGCTGGTGCAGATGGACCGCCGCGTCCACCTTGGGCCGCAGCACCTTGTGGAGTTGCCCGGCCGTGAGGGACGGGATGGTGCCGTCGTCGGTCACTCCGGCGGCGTGCACGACGCCGGTCAGCGGGTGCGCGGCGGGGATGCCCGCCAGCAGCTCCGCCAGCGCGTCGCGGTCCGCCGTGTCGCAGGCGGCGATTGTGACCTCGGCGCCCAGAGCGGCCAGTTCGTCGCGGAGCTCGGCCGCGCCGGGCGCGTCGCCACCCCGGCGGCTCGTCAGCAGCAGGTGGCGGACGCCGTGGGCGGTGATCAGGTGGCGGGCGAGCATGCCGCCGATGGTGCCGGTGCCGCCGGTGATCAGGACGGTGCCCTCGGTGTCCAGGCGGCGGCCGGGCAGGTCCGGCTCGGTCAGGTCGGTGTCCTGGCCGATACGGGCCAGGCGCGGCACCACCACTCCGCCGTGGCGCACCGCCACCTGCGGCTCGCCCGCCCCGAGCGCGACGGCGAGGGCACTGGGCAGCAGGGCCGCCGCGCCCTGGTCGGCGGAGGTGTCCTGGCCGGCGGCGTCGAGGTCGACCAGCAGGAGCCGGTCGATGTTCTCGAGCTGCGCGGAGCGCACCAGGCCCCACAGGGCGGAGTGCACCAGGTCGGCGACCCTCTCGTCGCCGCCCGTCGACTGGGCGCCACGGGTCACCAGCACCAGCCGGGAGTCGGCGAACCGCTCGTCCGCGAGCCAGTGTTGGACGACCCCGAGAAGGCGCGCGGTCTCGTCGTGGACCGCGGCGGCGAGCCCGGGGTCGGCTTCGGTCACCGCGCCGGCGAGGGGCGCACAGGGCAGCACCACCAGCTCGGCGGGCGGTGTGCCGTCGTCGACGGAGCGCGCCACCTCCGCGAGGTCCGGCGCGGTACGGACGGAATGTCCGGCCCGTTCCAGCGCGTCGGCGACGCCGAGGCCGTCGTCGCCCACCACCTCCCAGGCGCTTTCGGCGAGCACTCCGGGCTTGGGTTCGGCGGAGATCCACTCGACGCGGTACAGCGAGTCGAGCCCGGCATCGTCGCTGCGGCGCAGCTGCTCCAGGGAGACCGGGCGGGAGACCACCGCCTCGGCGGACGCGACCTGACGGCCCGAGGGGTCCGCGACGCTCAACGACACGCCGTCGGCCGTCGCGTTCGGCACCATACGGACACGCAGCGCGGCGGCCCCGGTGGCGTACAGCGACACACCGCTCCAGGTGAACGGGAGCAGCATCTGCCCGTCGGGCGTACCGCCCTGGCCGATGCCACCGGCTTGCAGCGCGGCGTCCAGCAGGGCGGGGTGCAACCCGAAACGCCCGGCCTCCTCCCGAAGTTCCTCAGGCAGAGCGGCCTCGGCGAACACCTCGTCCCCGCGGCGCCAGGCGGCCTTCAGGCCGCGGAACGCCGGCCCGTAGCCGTAGCCCGCCTCGGCCAGGCCGGTGTAGAGACCGTCCAGGGACAGCGGCTCGGCGTCGGCCGGCGGCCACTGGGTGAAGTCGAAGTCGTCCGGCCGGGCGCCCGTGGTGAGGGTGCCGCTCGCATGCCGGGTCCAGGTCCGGCCGGCGTCGTCGTGGCCGTCGGCGCGGCCGTCGTCGCGTGCGTGGACGGTGAAGGCGCGGCTGCCGTCCTGGCCCGGCGCGGAGACGACGAGCTGGAGTTGCAGCGCTCCCTCCTCAGGGAGGATCAGTGGGGCTTCGAGGACCAACTCCTCGACGCGGTCACAGCCGACCTCGTCCCCCGCGCGCACGGCGAGGTCGACGAACGCCGTGCCGGGCAGGAACACCGCACCGGCCACGGCGTGGTCGGCCAGCCAGGAGTGGCCGCCGGTGGAGATCAGGCCCGTGAGCACGACCTCCCCGCTGTCGGCGACCCGGACGGCGGCGCCGAGCAGCGGGTGGCCGGCCGAGCTGAGGCCGAGGCTCCGGGCGTCGCCGGAGCCGTTGAGGGTGGCGGGATCGATCCAGAAGTGCCGGCGCTGGAAGGGGTAGGTGGGCAGGTCGAGGACGGCCGGGGCTCGGGTGGTGGCACCGGAGGCGGCGTCGGCGGTGGCGTTCACCCCGTACCAAGCCTTCCAGTCCACCGGCAGCCCGGCCGCGAAGGCATGGGCCAGCGCCCGGGCCAGCTGCGCCGGACCACCCTGATCCCGCTGAAGGGTCGGCACGGTGGCCACCGCGACCTCGCCCGCCTGCGCGGTCTCCTGGATGCCCACGCTGAGTACCGGGTGCGGACCGGCCTCGACGAGCACGCGGTATCCGTCGGCCAACACGGCCTCGATCGCGGTGGCGAACCGCACCTGACGGCGCAGATTCTCCACCCAGTAGGTCGCGTCCAGCGTGGTGGTCTCCACCCGGCGGCCGGTCATGGCCGAGTAGAACGCGACCCCCGTGCCGATCGGTGTGATCTCCCCGAGCAGCGTGACCAGATCCTCGGCGATCTCATCCACCTGCGGACCGTGCGAGGCATAGTCCACATCGATCAGCCGCGCCCGCGCGCCGGACGCCTCGACCCCCGCGACCACCTCGGCCACCG CCTCGGGCGGACCCGAGATCACGGTGGAACCCGGACCGTTCACCGCGGCCACCACGACCCCGTCACGCCCACCGATGGCCTTCTCGGCCTCCTCAGCCCCCACCGCAAGCGAGGCCATCGCCCCCCGCCCCGACAACACCCGCAACGCCTGCGAACGCAACGCCACCACCCGGGCACCGTCCTCCAGCGACAGCGCCCCGGCCACCACGGCAGCGGCGATCTCGCCCTGTGAATGCCCCACCACCGCCGCAGGCACCACCCCATGGAAACGCCACAGCTCCGCCAACGACACCATCACCGCCCACAACGCGGGCTGCACCACATCCACCCGCGCCACATCCACCCCGTCCTCGCCCCGCAACACACCCGTCAACGACCAGTCGACATACGGCGCCAACGCCGCCTCACACTCCGCGATCCGCCCCGCGAACACCGGCGAAGAATCCAGCAGCTCCACCCCCATCCCCCGCCATTGACCCCCCTGACCCGGGAAGACCAGCACCGGCCCGGCACCCCCCGCCACCGGCTCGGCAGTCACCACACCACCCGACGGCACACCCTCCGCCAACGCCCCCAACCCAGCCAGCAGCTCCTCCCGGTCCTGGCCCACCACCACCGCGCGCTGCTCGAGCGTCGGTCGGCTGGCCACCAGCGACCACCCCACCTGCGCGGGGTCGGCCTGCGCCTCCTCGGCGTACTCGGCCAGCCGCTCGGCCTGGGCCCGCAGCCCCGCGGCCGAGCGCGCGGACACCACCCACGGCACCACACCGCCCACCGGCATCGGGTCGGGCCCGGCCGGAGCGTCCGGCTCCTGGGGCGCCTCTTCCACGATCACATGCGCGTTGGTGCCGGAGATGCCGAACGCCGAGACACCCGCCCGCCGCGGACGCTCCACCTCCTGCGGCCAGGCGGTGGCCTCCGTGAGCAGTTCAACGGCCCCGCTGCCCCAGTCCACATGCGGCGTCGGCTCATCCACATGCAACGTCCTGGGCAACACACCGTGCCGCATCGCCATCACCATCTTGATGACACCGGCAGCTCCGGCGGCGGCCTGGGTGTGGCCGATGTTGGACTTCACCGAGCCGAGCCACAAGGGCCGTTCCCGCGGCCGCTCCTGACCGTAGGTGGCCAGCACGGCCTGCGCCTCGATGGGGTCGCCGAGCGTGGTGCCCGTGCCGTGCGCCTCGACCACATCGACATCCGCCGACGAGAGCCGGGCGTTGGCCAGCGCCTGCCGGATCACCCGCTGCTGCGACGGACCGTTCGGCGCCGTCAACCCATTCGACGCGCCATCCTGGTTGATGGCCGTTCCGCGGATCACGCCCCACACCTGATGACCGTTGCGCCGCGCGTCCGACAGCCGCTCCAACAACAGCAGCCCTACGCCCTCGCCCCACCCCGTACCGTCCGCCGCCCCCGCGAACGCCTTGCACCGCCCGTCAAGCGCCAGCCCCCGCTGCCGCGAGAACTCCACGAAGGCACCCGGCGTGGCCATCACCGTCACGCCACCCGCCAGCGCCAGCGAGCACTCCCCGCCGCGCAGCCCGCGCACCGCCGAGTGGAGCGCCACCAGGGACGACGAGCAGCCCGTGTCCACCGTCACGGCCGGGCCCTCGAGCCCCAGCACATACGACACCCGCCCGGACACCACACACCCGAGATTGCCCGTGCCCTTGTACCCCTCCATGTCCATGCTGGAGATGCCGATGATCGACAGATAGTCGAAGATGGTCGCGCCGACGTAGACGCCGGTGTCAGTGCCGCGCAGCGAGCCGTGGTCGATACCGGCCCGCTCGAACGTCTCCCAGGCGGTCTCCAGCAGCAGCCGCTGCTGGGGGTCCATCCCCACCGCCTCACGCGGGGAGATCCCGAAGAAGTCGGCGTCGAACTCCCCCGCGTCGTAGATGAATCCCCCCTCGCGCACATAGCTGGTGCCGGGGCGGTCCGGGTCCGGGTCGTACAGCGTGTCGAGGCGCCAGCCGCGGTCGGTCGGGAACGCCGACATCGCGTCCCGGCCCTCGGCCACGAGGTCCCAGAGCTGTTCGGGGCTGCTCACCCCGCCCGGGAAGCGGCAGGCCATGCCGACGATGGCGATCGGCTCGTCAGCCTCCCCAGCCGGTCCCGCGGCGGGTACGACGGCGCCGGTGGCGGCCGCCTGTGTGCCGGAGATCTCCCCGAGGAGGTGGCGGGCGAGGTCGTCCGCGGTGGGGTAGTCGAAGATCAGCGTGGTGGGCAGCGGCATCGCGGCGCTGGAGCTCAGCTTGTTGCGCAGCTCGACGGCGGTCAGCGAGTCGAAGCCCATCTCGAAGAAGGGCTTGGTCGCGGACACCGCGTCCGGGCCCGCGTGGCCCAGCACGCCGGCCGCGAGGGCGCGGATGTGCTGCGAGAGTATCTGGTGGCGCTGTTCCGGGGCAGCCGCGGCCAGTTGCCTGCGCAACGGGCTGTCCTCGGACGGCGTCTCCTTCTCCAGCAGTTCGACGGCCTCGGGGATGTCGGCGAGGAGTTGGCTGGCGCGCTGGCCGGCGAATGTCGCGGCGAACCGCCGCCAGTCGAAGTCGGCCACCGTCAGCGCCGTCTCGCCGCGGCCCAGGGCGTCGCCCAGCACCCGCAGCGCCAGCTCCGGCGCCATGGCGGTCAGACCCCGCTCGCGGAAGAAGGCCGCGACCGTGTCATCGGCGGCCATGCCCGCCTCGCCCCAGGGGCCCCACGCCACCGACAGGCCGGGCAGGCCCTCGGCGCCGCGGCGTTCGGCCAGCGCGTCCAGATACGCGTTGGCCGCCGCGTACGCGCCCTGCTGGCCACTGCCCCAGCTGGCGGCGCCGGAGGAGAACATCACGAACGTCGACAGGTCCATGTCGCGCGTCAGCTCGTCGAGCCACCGCGCGCCCCCCGCCTTCGCGGCCAGCACCTGTGCCACCCGGTCCGGGTCCAGGTCGCCGACCGGCGTGTAGTCGCCGACCCCGGCGGCGTGGAAGACCCCGCGCAGCGGCTGCCCTTCCGGCACCCGGGCCAGCAGCCCGGCCACCTCGTCGCGGTCCGCGACATCGCAGGCCACCACGGACACCGAGGCGCCAAGCCCCTCCAGTTCGGCCGTCAGCTCCTCGGTCCCCGGCGCCGTGGGGCCGCGCCGGCTGGCCACGATCACATGGCGGGCCCCGCGCTCCACCACCCACCGTGCGACGCGGCCACCCACTCCGCCCGTCCCGCCGGTCACCAGGACCGACCCCTCGATCCGCCACTCCTCATCCGGCGCGCCGCCCGACGCCGCACGCAACCGGCGTCCCAGCGCGCCCCCGGCGCGCAACGCCACCTGGTCCTCCGTGCCCGCGGCCAGCACCGCGGCCAGCCGGCTCGGCGTCCCCTCCTCCCCGGCCGCCGGCAGGTCGACCAGGCCGCCCCACCGCTTCGGGTACTCCAGGGCCACCACCCGCCCCAGGCCCCACACCTGCGCCTGCACCGGGCTCACCGAGCCGTCCTGGCCGACGGCCACGCCCCCGCGCGTGACACACCACAGGCGCCCGGCGAACTCCAGCTCGTCCAGC GCCTGCACCAGGGCGAGTGTCCCGGCCAGCCCCGCCGACAGGTGCGGATGCTCCGGGTGTCCGGCCTCGTCCAGGCTCAATACGCTGACCAAGCCGACGACTTCGGGCCAGCCCTCCACCTGCCGCAGACGCGTCGCGAGGAGGCCGCGCTCCTGGTCTTCCGGCGCCACCGCGAAGACCGCGCACCGCGCCCCATGGTCCGCGAGCGCCCCGGCCACCAGCTCGGCCACCGGGTCCCCGACCAGCTTCTCGGGCACCACCAGCAGCCATGTACCGCTCAGCCGGGGAGTCTCGTCCAGGCCGGTCACGGCGGACCAGGCGGTCAGGTAGCGCCAGGCGTCGATCCGGGCCTGGTCGCGCGTACGCCGGCGCCACTGCGCCAACACGGGCAGCGCCGGAGCCAGCACCTGCCGCGCGGTGTCCTCCCCCAGGCTCAGCGACGCCCCGAGTCCGGCGAGGTCCCCCGCCTCGATGGCGCTCCAGAAGCGCTCGTCCTCCTCGGAGCCCTTCTCCTGGGAGCCCGGCCATGTGCCCGGCTTCAGCCAGTAGTGCCGGCGCTGGAAGGGGTAGGTGGGCAGGTCGAGGACGGCCGGGGCCCGGGTGGTGGCGGCGTCGGCGTTCGTGCTCACCCCGTACCAGGCCCTCCAGTCCACCGGCAGCCCGGCGGCGAAGGCGTGCGCCAGGGCCCGGGCCAGCTGCGCCGGACCGCCCTGATCCCGCTGCAGGGTCGGCACGGTGGCCACCGCGACCTCACGCTCCTGAGCGGTCTCCTGGATGCCCACGCTCAACACCGGATGCGGGCCCGCTTCCACCAGCACCCGATAGCCCTCGGCCAGCACCGCCTCGATCGCGGTGGCGAAACGGACCTGACGGCGCAGGTTCTCCACCCAGTACCTGGCGTCCAGCGTCGTGGTCTCCACCCGGCCGCCGGTCACCGTCGAATAGAACCCCACCGTGGTGTCCACCGGTGTGATCTGCCCCAGCAGGGCCACCAGGTCCTCGGCGATCTCGTCCACCTGCGGACCGTGCGAGGCGTAGTCCACATCGATCAGCCGCGCCCGACCACCGGACGCCTCCACCACGGCGACCACCTCGGACACCGCCTGCGGCGGCCCGGAGACCACCGTGGAACCAGGCCCGTTCACCGCCGCCACCACAACACCCTCACGCCCCGCGATGGCCCTCTCCGCCTCCTCAGCCCCCACCGCAAGCGAGGCCATCGCACCCCGCCCCGACAACACCCGCAACGCCTGCGAACGCAACGCCACCACCCGGGCACCATCCTCCAGCGACAACGCCCCCGCCACCACCGCGGCAGCGATCTCGCCCTGTGAATGCCCCACCACCGCCGCAGGCACCACCCCATGGAAACGCCACACCTCCGCCAACGACACCATCACCGCCCACAACGCGGGCTGCACCACATCCACCCGCGCCACATCCACCCCGTCCTCGCCCCGCAACACACCCGTCAACGACCAGTCGACATACGGCGCCAAAGCCGCCTCACACTCCGCGATCCGCCCCGCGAACACCGGCGAAGAATCCAGCAGCTCCACCCCCATCCCCAGCCACTGACCCCCCTGCCCCGGGAAGACCAGCACCGGCCCGGCACCCCCCGCCACCGGCTCCGCCGACACCACCCCACCCGACGGCACACCCTCCGCCAACGCCCCCAACCCGGCCAGCAGCTCCTCCCGGTCGCCGCCGATGACCACGGCCCGGTGTTCGAGCATCGCCCGGCCGGCGGCCAGCGACCACCCCACCTCCTCCGCATCGGCGGTGGTCCGCTCGGCGTACTCGGCCAGCCGTCCGGCCTGGGCCCGCAGCCCCGCGGCCGACCGCCCGGAGACCACCCACGGCACCACACCGCCCGGAGCGGTCGGCTCGGTGGTTTCCCCCTCCGTGGGGGGCTCGGGCGCCTCCTCCAGAATCACATGCGCGTTGGTGCCGGAGATGCCGAACGCCGAGACACCCGCCCGCCGCGGACGCCCCGCCTCCTCCGGCCAGGCGGTGGCCTCCGTCAGCAGCTCGACCGCCCCGCCACCCCAGTCCACATGCGGCGTCGGCGCGTCCACATGCAACGTCTTGGGCAACACCCCATGCCGCATCGCCATCACCATCTTGATGACACCGGCGACACCGGCGGCGGCCTGGGTATGGCCGATATTGGACTTGATCGACCCCAGCCGCAGCGGCCGCTCCTCGGGCCGCGCCTGGCCATAGGTCGCCAACAGCGCCTGTGCCTCGATCGGGTCGCCGAGGGTGGTGCCCGTCCCGTGTGCCTCGACCACATCGACATCCGCCGGCGAGAGCCGGGAGTTGGCCAGCGCCTGCCGGATCACCCGCTGCTGCGACGGACCGTTCGGCGCCGTCAGCCCATTCGACGCACCGTCCTGATTGATCGCCGACCCACGCACCACCGCCCACACCCTGTGACCATTGCGCCGCGCATCCGACAACCGCTCAAGCAGCAGCAACCCCACCCCCTCACCCCACCCCGTACCATCCGCCGCCCCCGCGAACGCCTTGCACCGCCCGTCCAGCGCCAACCCCCGCTGCCGCGAGAACTCCACAAACGCACCCGGAGTGGCCATCACCGTCACCCCACCCGCCAACGCCAACGAGCACTCGCCCCCGCGCAGCGCCTGCACCGCGGAGTGCAGCGCCACCAGGGACGACGAGCAGCCCGTGTCCACCGTGACGGCCGGACCCTCAAGACCCAGCACATACGACACCCGGCCGGAGAGCACACATGCGAGGTTCCCGGTGGCGGCGTAGCCCTCCACCTCGCTGCCGGCCATGGCGGTGAGCACCATGTACTCCTGCGAGGTCACCCCGGCGTAGACGCCCGTGCTGCTGCCCACGAGGCCCTGGGGGTCGATGCCGGCGTGTTCGAAGGTCTCCCAGGCGACCTCCAGCAGCTGCCGCTGCTGGGGGTCCATCGCCAACGCCTCACGCGGTGAAATACCGAAGAATTCCGCGTCGAATTCCCCGGCCCCGCGCAGAAAGGTGCCCTCGCGCACATAACTCGTTCCCGGGCTGTCCGGGTCGGGGTCGAAAAGGTTCTCCAGATCCCAGCCGCGGTCCTGGGGAAATGCGGTCAGCCCCTCGCCTCCGGCCGCCACGAGTTCCCACAAGTCCTCCGGGTTCTCCACCCCGCCCGGAAAACGGCACGCCATACCGACGATCGCGATCGGCTCGGGTTCCGCGGACTCCGCTTCGCGCAGACGCTGCCGGGTGTCCCGCAGTTCTGCCGTCACCCACTTGAGGTGGTCGAGAAGCTTCGCCTCGTCCTTCGCCATCGCTGGCGCCTCCCCTCCTGGCGGTTTTCTTCTTGGCTGTCGGCGTCAGAACGTGGTCAGAGTGTGGTCAGAATGTGCAGCGCAGTTCTTTGAAGCCCTCGATGAAGCTCGATGCCACACGGACGGGTTCGCCGTCCACGCGGATGTCCGGCAGTGAGGTGAAGAGTTCGCGGCACATGGCGACGATCTCGATACGGGCGAGATGGGCGCCCAGACAGAAGTGCGGCCCCACCGCGCCGAACG CCAGATGAGGGTTGGGGTCGCGGGTGATGTCGAACCGGTACGGATCCTCGAAGACCTTCTCGTCGTGGTTCGCGGACCAGTAGAAGAGGAAGATCTCGTCGCCCTTGCGGAACCGGTGGCCGTTCATCTCGCAGTCGCCGGTCGCGGTGCGGCGCATCCAGTTGATGGGCGTGCCCACGCGAAGGATCTCCTCGACGGCGTTCTTCGCGTGGGTCTCGAAGTCCGAGAGCAGGAGTTCCCGCTGGTCGGGGTGGGTGGTGAGCAGTACCAGGGCCTGGGCGATGGCGTTGCGGGTGGTCTCCATGCCGGCGTTGACGAGGAGGATGAAGAACGAGACCAGTTCCTGGTGGGTCAGTTGTTCGCCGTCCTCCTGCACCTGGACCAGCTTGGTGATCACATCGCCGGTGGGGTGGGCGAGCCGGTCCTCGCGGAGCCGTCCGATGTAGTTCCCGAGGTCCCGCAGGGCGCCCAGCACGGCGGCCGCCGCGCCCTCGGGGCTGGCCGTGTGTTCCGGGTCGACCCCTCCCATGATGGTGTTGGTCCGCTCGAAGAGGAATTCGTAGTCCTCGCCGGGAATTCCCATCATGGTGCTGAGGACGGCGATCGGCATCTCCGCCGCCGGGCGGATGAAGTCGCCGGGTCCGCGCTCGATGAGCTCGTCCACGATGCGCCGGGCCACCTGCCGTGACATGGCGTCGAACCTGGGAGCCATACCGCGGCCGAACGACCGCGCCACGATGCGCCGCAATCGGGAGTGCTCCGGATTGTCCATGTTGATCATGGAGCCGTAGAACTCGTCCATCTCCGGCGGCAGGATCGAGGTGGCGCCCTCCGAGGAAAAGTCCTGCGGACGGCGGCTCACTTCCGCGATGTCGGCGTGTTTCACCATCGCGTAATAGCCGTTTGCCAACGGCCCCCAGGGCAGCCGCGGCGGAACGAATTCCGGGTGCGGCAGCCCGCGCAGCCTCTCGAACACCGCCGCCCGCTCCTCATGCGGCCGTAACCAGAAGGACGGATCCATGAAGTCGGGACACGTGGCGGCGGTGGTGGCGGAACGGGACGTGGCTTCCGAAGGAGACACAATGCCTCGATTCAAGCTTGGACAGGTACGAAAACCGGTCCGCGCAAGTCTCACAAGGCCCTCTAAAGAGTTCCTAACAGCCTGAGGGCCCAGGGGCGATTGACGTCGGGGGGACGGGGTGCCAGCCTCGGGGCGTGCAGGTGACGATGACCGGAGGTAGCGGGCGCGATGGATCCACTCGCCGGTCTCCTGGACGGGCCGAGGGCCCGGGGGGCGTTTCTGCTCCGGATGGTCATGGAACCGCCCTGGTCGGTGCGGATCGAGGACCGGGCCCCGCTGTGTGTGATGACCGTGGCGCGCGGTGAGGCGTGGGTGATCCCGGACCGGGGCGGGCCTGAGAAGGGGGTGCGGCTGGGCCCGGGGGATGTCGCGGTCGCGCGCGGCCCCGACCCGTACACGGTGGCCGGCGATCCGGCCACCGAGCCCCAGGCCTGGATCCTGCCGGGCGAGGTGTGCCGGACCGCCGCGGGCGAGGACCTGGCGGAGCGGATGGCGCTGGGCGTGCGGACGTGGGGCAACAGCGAGCACGGCTCGGCGACGATGCTGGTCGGCACGTACCGGATGGACGGCGAGATCAGCCGCCGGCTGCTGGACGCGCTGCCCCCGCTGCTGGTGGTGCCGGGTGAGGCGTGCGACTCGCCGTTGCTGCCGTTGCTCGGCGAGGAGATCGTCAAGGAGGAGGCGGGCCAGACGGCGGTCCTTGACCGGCTGCTGGATCTGGTGCTGATCTCCGTGCTGCGGACGTGGTTCTCCCGCCCGGAGGCGCGGGCCCCGGCCTGGTACCGGGCGCTGGGCGACCCCGTGGTCGGCCGCGCCCTGCGGCTGCTGCAGAACAACCCGGGCCATCCGTGGACGGTGGCCCTGCTGGCCGCGGAGACCGGGAGCTCCCGCGCGGCGCTGGCCCGCCGCTTCACGGAGCTGGTCGGCGAGCCGCCGATGGCGTATCTGACCGGCTGGCGGCTGGATCTGGCCGCCGATCTGCTGCGGGAGCCGGACGCCACCCTCGGGGCGGTGGCCCGCCGGGTCGGCTACGGCAGCTCGTTCGCGCTGAGCGCCGCCTTCAAGCGGGTGCGCGGCGTCAGCCCGCGGGAGCACCGCTCCGCGGCCAGCGCAGGGTGACGGCGGGACCGCGGGCACAGCCGTCCGGCCCGCAGCTGACGGAGCGTTCGTACAGCAGGGTCAGACGGCGGGCGGTGCGGATGATGTCGTAGCGCTCGACGGCGGCGGGCACCGGGTACCGTACGGGGCCGGCGGCGGCCCGCTGGCGCAGGGCGTCGGCCAGGGCGTCGGCACCGGGGCCGACGCGGCGGGCGCCGGGGGCGGCGCCGGGCGGCAGTTCGTCGAGGGCCGGGCAGACGCCGTGGAGCACGGGGAGCCCGGCCGCCAGGGCCTCCACGGCGGCGAGCCCGAACGCCTCCTCGGCGGACGGTGCCACGAACACGTCCATGGCGGCCAGCAGCCCGGGGATGTCCGCGGGCCGGTCCCCGGTCCCGGCCACCGCCCCGTCGCGCTCGCCGAGCAGCCGGATGCGGTCGGCCACCCCGAGCCAGGCGGCCAGGTCGTGCAGCGCGGTGCGCTCGGGCCCGTCCCCGACCAGCAGCAGCCGGGCCTGGGGCACCTCGGCCACGGCCCGCAGCGCCACATCGAAGCGCTTGGCCGCCACCAGCCGGCCGATCCCGCCGACGACGAAGGCGTGTGCGGGGATGCCGAGGCGGGCGCGGGCGGCGGCCCGGGCGGCGGGGGTGAAGCGGAAGTGGCCGGCGTCCAGGCCGTTGGGCATCAGGTGGATGCGGTGGTTGGCGACGCCCCAGCCGCGCAGCCGGTCGGCGACGGCGGCCGAGACGGCGACGGTCGCCGAGCCCAGGCGCTCGGTGGCGAGGTAGCGGGCGCGGGTGCCGACGGTGAGCGGGCGGCCGTCGATGTGGCGCTCGCCCAGGCTGTGCTCGGTGGCGATCACGGCGCCGACGCCCGCCAGCCGGGCGGCGATCCGGCCGTGCACGCAGGCCCGGTAGAGATGGGTGTGCACCAGGTCGTAGCCGCCGCCGCGGATGAACCGCGCCAGCCGGGCCGGTGCCATCGGGTCGCGGACGCCGATCGGCAGATGGGTGACGGGCACGCCGTCCGCCCGGATGCCGTGGCCGGCGGTGCCGGGCGCGGCCAGGGTGAGGACGTCACAGCGGGCGGGCAGGTGGCGCAGCAGCAGCCGTAGTTGCTGTTCGGCGCCACCCGCGCCGAGGCGCGAGATGATGTGCAGCACTCTCATCGGGCGACCGGGCCCCATCTTCCGTATGTCGCACGCCTTATGGCGCGGGTTTACTCGCGCATCCCGCACCCACAGCCCTCACGCGCGGTCGAAACATGCACGCTGAATCGCATCCGACCATGACAGATGGCGGGATGTAAATCACGTAAGACGCGCGGCGATAGGCCGTCGGAGTGGCGGCCCGCCCG GTGCGTCGGCGAAGCGCGGCAGGGCGCGCCGAAAATCCGATTTGCACAGCCATTCCCCAGCGGATTGTTACCTTCTCATCTCGCGCGATGACATGACGAATGTAGGCCGTCCGGGTCATCGCCGCGCGATATTGCGTCCCCGACGACCCGCGGGAGTGCCCAGATGTCCGCACCTACCCCCGTCAGAGACACGGCCGAGAAGGGTGCCGCGCCCAGTGTCGCTCCCCCGCCCGCGCGGCCCGCGCACCACGAGATGGCCTCCCGCCGCGGGGGCCCGGCCGGGCGTTATGAGTACAAGCGGTACAGCCAGCTGGCGGGCCCGCTGACGCAGCCCCCGACCGGCCGCCCGTACCGGGTGCGCTGCCGGAGCCTGCTGGCGCAGGAGCCGCACCGGGTCCGCGCGGCGCTGCTGCTGTGCGCGGCGCCGGTGTGCTCGGCGCTGCTGCTGCTGTGGCTGCTGCAGCCCCAGCACTGGGTGCACCGCGACGGTGTGGCGGGCTGGGAGACGGCCGCGGACCGGACGATGCTGTTCTCGATCGCGCTGATCGAGGCGTTCCGCCTGTTCACCGTGGTCTCCAACGCGCACGCCACACTGGTGGCCCGCGACCCGGTACCGGTGACCGCCGAGCCCGGGACCCGGGTGGCCTTTCTGACCAGCTTCGTCCCCGGCAAGGAGCCGATCGAGATGGTCCGGGCGACGCTGGAGGGGGCCAAGCAGGTCAGACACGCCGGGGGACTGGACGTATGGCTGCTCGACGAGGGAAATGACGAGGAGGCCAAGGAGCTGTGCGCCCGGCTGGGCGTACGGCATTTCTCCCGCAAGGGCGTCGAGAAGTGGAATCAGCCCAAGGGCTCCTTCCGCGCCAGGACCAAGCACGGGAATTACAACGCCTGGCTTGACGCCCATGGCGACGACTATGAATTCATGGCCTGTGTGGACACCGATCATGTGCCGCTGCCCAACTTCCTCGAGCGCATGATGGGTTACTTCCGCGATCCGGACGTCGCCTTCGTGGTCGGCCCGCAGGTGTACGGAAATTACGACACGGCGGTCACCAAGGCGGCCGAGAGCCAGCAGTTCCTCTTCCACGCGCTGATCCAGCGGGCGGGCAACGCGTACGGCGGCCCGATGTTCGTCGGGACCAACAACGCGGTGCGCATCGCCGCGCTGCGGAGCATCGGCGGTCTTTACGACTCGATCACCGAGGACATGGCCACCGGCTTCGAGCTGCACCGCCGCCGCAACCCCGCCACCCGGAAGAAGTGGCGCTCGGTCTACACCCCGGACGTACTGGCCGTCGGGGAGGGCCCGAGCACCTGGACGGACTTCTTCACCCAGCAGCTGCGCTGGAGCCGCGGCACCTACGAGACGGTGCTCAAGCAGTTCTGGAAGGCGCCGTTCACGCTCTCGCCGGGGAAGCTGCTCAACTACTCGCTGATGATCGCCTACTATCCGATGACCGCGCTCAACTGGATGCTGTCGGCGCTGTCCTGTGCGCTGTTCCTGGTGCTCGGGGCGTCCGGGATCCAGATCCCGGCGGAGATGTGGATGATGCTCTACAGCGACGCCGCGGCGCTGCAGATCGGCCTGTACATCTGGAACCGGCGGCACAACGTCTCCCCGCACGAACCGGAGGGCTCCGGCGGGGTGGCGGGGATGCTGCTCTCGGCGCTGTCCGCCCCGATCTACGCCAAGTCGCTGTGCGACGCGCTGCTGCGGCGCAAGAGCCGGTTCGTGGTCACGCCCAAGGGCGACTCCTCCAGCGCCGACCGGCTGTCCACCTTCCGTATCCATCTGGTGTGGGCCGTGGTCTTCGGCGGCTCGCTGGTCGCCTCGCTGTTCCTGGGCCACACCCACGCGGCGATGCGCACCTGGGCGCTGCTGGCGCTGGCGCTGTGCCTGGCGCCGATGGCTATCTGGTCGGGCGGGCTGCTCCTGGCGCGGCGCGGGCGGCGCACCGCCCCGGCGGTGCCGACGGCCCGCGCCGAGGCCCACTGACGGAGCGCGCCCGCCCCGTCCTCATCTGTCGCGCACCATGGCGTTGCGGGCCAGGTCGAGCGCGTACTCCGTCCACCAACGGCCGGCCGGGGGGCCGCCGTTGCAGGTCCCGTCGGACTCGCCGGGGCGCTTGATCCACAGATACGCGTCGATGGCGGGGTCGCCGGTGCGGGTGCTCGGGGGGTCCCCCAGGGCCCGCCCCGGGGGGTTGCACCAGTTCTCCTGGTCGTCGCTGGCGGAGCGTACGGCGCCGGTCTCACCGCTCTTGCCGTCGTCGCCCTCGCCCCTGGCGGGGCTGAGCGGGCCGTTGCCGTTGCGGCTGGTGTCGATGATGAAGTGGACCCTGCCGAGCTGGGTGGACAGGCGACGGCCGTAGGCGCGGGTCACCGAGGTCGGCTGGAAGTTCGAGACGTTCAGGGCGAAGCCGTCCGCCTGGTCGATGCCGGCCTTCATGAGCGGCTCCACCAGCCGCTCGGTGTCCCTGATCCACCCCGGGTTGCCGGCGTCCAGGTAGATCCGGGTGGCGGGCATCGCGGAGAGCATGGCGACCGCGTCGCGCAGCAGGGCCAGCCGTGGCGCCCGCAGCGGCTTGGGAACGCAGCCGTCGACCACCTGGGCCACCGCGTCGGGCTCCAATACGACAATCGCTTTTCGTTCGCCGATTCCGGAGACGATCTCACGGATCCAGTCCAGATATTCGGCGTCGTTCCTCGCCCCGCCCCGGGAGTATCTTCCGCAGTCCCGGTACGGAATGTGATAGGCGACCAGCACCGGCACCCTGTTCTGCCGCGCCGCGGATTCGGTGACGAACCGGACCCGCTCGCGCGGATGCGGGCCCAGCCATTCGGCGATCGGCTCGTCGGCGATCCGCCGCATGAGCTCCGCCTCCGCGTACCGGCCGGCGCGCCGCTGCTCACGGGCCTGCCGGGCGGCCGGGCTGTCCGGGTTCAC(SEQ ID NO:36)
the explanation of the biosynthetic gene cluster is given by taking the biosynthetic gene cluster of the streptomyces as an example, and the biosynthetic gene cluster comprises a linear polyketide synthase gene module I, a glycosyl synthesis related gene module and a modifying gene module. The modules of the biosynthetic gene cluster of Streptomyces are described in detail below, specifically as follows:
wherein, the I type linear polyketide synthase gene module comprises 11 genes of 3A1, 3A2, 3A3, 3A4, 3A5, 3A6, 3A7, 3A8, 3A9, 3A10 and 3A11, and the specific details are as follows:
according to an embodiment of the invention, the 3a1 gene encodes SEQ ID NO: 1, as shown below. According to the embodiment of the invention, 3A1 is located at 5773-14433 bases of the gene cluster nucleotide sequence, is 8661 base pairs in length, encodes polyketide synthase and is 2886 amino acids in length.
Figure BDA0000889460040000331
Figure BDA0000889460040000341
Figure BDA0000889460040000351
According to an embodiment of the invention, the 3a2 gene encodes SEQ ID NO: 2, as shown below. According to the embodiment of the present invention, 3A2 is located at 14448-21131 th base of the gene cluster nucleotide sequence, is 6684 base pairs in length, encodes polyketide synthase, and is 2227 amino acids in length.
Figure BDA0000889460040000352
According to an embodiment of the invention, the 3a3 gene encodes SEQ ID NO: 3, as shown below. According to the embodiment of the invention, 3A3 is located at 21191-33316 base of the gene cluster nucleotide sequence, has the length of 12126 base pairs, encodes polyketide synthase and has the length of 4041 amino acids.
Figure BDA0000889460040000353
Figure BDA0000889460040000361
Figure BDA0000889460040000371
According to an embodiment of the invention, the 3a4 gene encodes SEQ ID NO: 4, as shown below. According to the embodiment of the invention, 3A4 is located at 33337-45120 bases of the gene cluster nucleotide sequence, has a length of 11784 base pairs, encodes polyketide synthase and has a length of 3927 amino acids.
Figure BDA0000889460040000372
Figure BDA0000889460040000381
According to an embodiment of the invention, the 3a5 gene encodes SEQ ID NO: 5, as shown below. According to the embodiment of the present invention, 3A5 is located at 45166-57099 bases of the gene cluster nucleotide sequence, is 11934 base pairs in length, encodes polyketide synthase, and is 3977 amino acids in length.
Figure BDA0000889460040000382
Figure BDA0000889460040000391
Figure BDA0000889460040000401
According to an embodiment of the invention, the 3a6 gene encodes SEQ ID NO: 6, as shown below. According to the embodiment of the invention, 3A6 is located at 57120-62141 bases of the gene cluster nucleotide sequence, has the length of 5022 base pairs, encodes polyketide synthase and has the length of 1673 amino acids.
Figure BDA0000889460040000402
Figure BDA0000889460040000411
According to an embodiment of the invention, the 3a7 gene encodes SEQ ID NO: 7, specifically the following amino acid sequence. According to the embodiment of the invention, 3A7 is located at 71586-76577 bases of the gene cluster nucleotide sequence, has the length of 4992 base pairs, encodes polyketide synthase and has the length of 1663 amino acids.
Figure BDA0000889460040000412
According to an embodiment of the invention, the 3A8 gene encodes SEQ ID NO: 8, as shown below. According to the embodiment of the invention, 3A8 is located at 91418-101764 bases of the gene cluster nucleotide sequence, has a length of 10347 base pairs, encodes polyketide synthase and has a length of 3448 amino acids.
Figure BDA0000889460040000413
Figure BDA0000889460040000421
Figure BDA0000889460040000431
According to an embodiment of the invention, the 3a9 gene encodes SEQ ID NO: 9, as shown below. According to the embodiment of the present invention, 3A9 is located at 82460-84850 base of the gene cluster nucleotide sequence, is 2391 base pairs long, encodes polyketide synthase, and is 796 amino acids long.
Figure BDA0000889460040000432
According to an embodiment of the invention, the 3a10 gene encodes SEQ ID NO: 10, as shown below. According to the embodiment of the present invention, 3A10 is located at 77532-77846 base of the gene cluster nucleotide sequence, and is 315 base pairs long, and encodes ACP protein of polyketide synthase, and is 104 amino acids long.
MEPTNGSPDD GQLADRLASA APEERQQLLC ELVLRRAAEI LDVPSLDEES NFLENGLSSL 60
TAVKLSKFLM DDTGIEVPLV SIVEHPTSTL LGKYLAEAYA ADAA 104(SEQ ID NO:10)
According to an embodiment of the invention, the 3a11 gene encodes SEQ ID NO: 11, as shown below. According to the embodiment of the present invention, 3A11 is located at 84902-91405 bases of the gene cluster nucleotide sequence, has a length of 6504 base pairs, encodes polyketide synthase and has a length of 2167 amino acids.
Figure BDA0000889460040000433
Figure BDA0000889460040000441
The glycosyl synthesis related gene module comprises 9 genes of 3G1,3G2,3G3,3G4, 3G5,3G6,3G7,3G 8, 3M and 3G9, and the specific steps are as follows:
according to an embodiment of the invention, the 3G1 gene encodes SEQ ID NO: 12, as shown below. According to an embodiment of the present invention, 3G1 is located at 69443-70255 bases of the gene cluster nucleotide sequence, is 813 base pairs long, and encodes glucose-1-phosphate: TTP thymidine transferase, 270 amino acids in length.
Figure BDA0000889460040000442
According to an embodiment of the invention, the 3G2 gene encodes SEQ ID NO: 13, as shown below. According to the embodiment of the present invention, 3G2 is located at 68454-69446 bases of the gene cluster nucleotide sequence, is 993 base pairs long, encodes dTDP glucose-4, 6-dehydratase, and is 330 amino acids long.
Figure BDA0000889460040000443
According to an embodiment of the invention, the 3G3 gene encodes SEQ ID NO: 14, as shown below. According to the embodiment of the present invention, 3G3 is located at base 67107-68411 of the gene cluster nucleotide sequence and is 1305 base pairs in length, encodes NDP-D-glucose-3, 4-dehydratase and is 434 amino acids in length.
Figure BDA0000889460040000444
According to an embodiment of the invention, the 3G4 gene encodes SEQ ID NO: 15, as shown below. According to the embodiment of the present invention, 3G4 is located at 66055-67110 th base of the gene cluster nucleotide sequence, has a length of 1056 base pairs, and encodes NDP-D-glucose-4, 6-dehydratase, NDP-D-glucose-4-isomerase, and NDP-D-glucose-4-reductase having a length of 351 amino acids.
Figure BDA0000889460040000451
According to an embodiment of the invention, the 3G5 gene encodes SEQ ID NO: 16, as shown below. According to an embodiment of the present invention, 3G5 is located at 63620-64924 bases of the gene cluster nucleotide sequence, is 1305 base pairs in length, encodes a glycosyltransferase, and is 434 amino acids in length.
Figure BDA0000889460040000452
According to an embodiment of the invention, the 3G6 gene encodes SEQ ID NO: 17, as shown below. According to an embodiment of the present invention, 3G6 is located at 104167-.
Figure BDA0000889460040000453
According to an embodiment of the invention, the 3G7 gene encodes SEQ ID NO: 18, as shown below. According to the embodiment of the present invention, 3G7 is located at 105793-107538 bases of the gene cluster nucleotide sequence and has a length of 1746 base pairs and encodes glycosyltransferase and has a length of 581 amino acids.
Figure BDA0000889460040000454
According to an embodiment of the invention, the 3G8 gene encodes SEQ ID NO: 19, as shown below. According to the embodiment of the invention, 3G8 is located at 107560-108489 bases of the cluster nucleotide sequence, is 930 base pairs long, and encodes endoglucanase enzyme, and is 309 amino acids long.
Figure BDA0000889460040000455
According to an embodiment of the invention, the 3M gene encodes SEQ ID NO: 20, as shown below. According to the embodiment of the invention, 3M is located at 65099-66031 base of gene cluster nucleotide sequence, and is 933 base pairs in length, and encodes methyltransferase, and is 310 amino acids in length.
Figure BDA0000889460040000461
According to an embodiment of the invention, the 3G9 gene encodes SEQ ID NO: 21, as shown below. According to the embodiment of the present invention, 3G9 is located at 70469-71494 bp of the gene cluster nucleotide sequence, is 1026 bp in length, encodes glycosyltransferase, and is 341 amino acids in length.
Figure BDA0000889460040000462
Wherein, the modifying genes comprise 5 genes of 3O,3I, 3E, 3P1,3P2 and 3P3, and the specific genes are as follows:
according to an embodiment of the invention, the 3O gene encodes SEQ ID NO: 22, as shown below. According to the embodiment of the present invention, 3O is located at 77897-79321 bases of the gene cluster nucleotide sequence, has a length of 1425 base pairs, encodes cyclooxygenase, and has a length of 474 amino acids.
Figure BDA0000889460040000463
According to an embodiment of the invention, the 3I gene encodes SEQ ID NO: 23, as shown below. According to the embodiment of the invention, 3I is located at 79410-80351 bases of the gene cluster nucleotide sequence, is 942 base pairs in length, encodes ketosteroid isomerase and is 313 amino acids in length.
Figure BDA0000889460040000464
According to an embodiment of the invention, the 3E gene encodes SEQ ID NO: 24, as shown below. According to the embodiment of the invention, 3E is located at 76579-77424 bases of the gene cluster nucleotide sequence, is 846 base pairs in length, encodes epoxide hydrolase and is 281 amino acids in length.
Figure BDA0000889460040000465
According to an embodiment of the invention, the 3P1 gene encodes SEQ ID NO: 25, as shown below. According to the embodiment of the present invention, 3P1 is located at 62303-63502 bases of the gene cluster nucleotide sequence, is 1200 base pairs long, and encodes cytochrome P450 protein, and is 399 amino acids long.
Figure BDA0000889460040000466
Figure BDA0000889460040000471
According to an embodiment of the invention, the 3P2 gene encodes SEQ ID NO: 26, as follows. According to the embodiment of the invention, 3P2 is located at 81086-82375 bases of the gene cluster nucleotide sequence, is 1290 base pairs in length, encodes a cytochrome P450 protein, and is 429 amino acids in length.
Figure BDA0000889460040000472
According to an embodiment of the invention, the 3P3 gene encodes SEQ ID NO: 27, as shown below. According to the embodiment of the present invention, 3P3 is located at 101832-103028 bases of the gene cluster nucleotide sequence, is 1197 base pairs in length, encodes cytochrome P450 protein, and is 398 amino acids in length.
Figure BDA0000889460040000473
According to an embodiment of the present invention, the biosynthetic gene cluster further comprises: a regulatory gene module comprising: 3R1 gene, 3R2 gene, 3R4 gene, 3T1 gene, 3T2 gene, 3T3 gene, 3T4 gene and 3T5 gene, wherein the sequence information of the genes is as follows:
according to an embodiment of the invention, the 3R1 gene encodes SEQ ID NO: 28, as shown below. According to the embodiment of the invention, 3R1 is located at 3519-4259 bases of a gene cluster nucleotide sequence, is 741 base pairs in length, encodes a regulatory protein and is 246 amino acids in length.
Figure BDA0000889460040000474
According to an embodiment of the invention, the 3R2 gene encodes SEQ ID NO: 29, as shown below. According to the embodiment of the present invention, 3R2 is located at 4321-5082 bases of the gene cluster nucleotide sequence, is 762 base pairs in length, encodes a regulatory protein, and is 253 amino acids in length.
Figure BDA0000889460040000475
According to an embodiment of the invention, the 3R4 gene encodes SEQ ID NO: 30, as shown below. According to the embodiment of the present invention, 3R4 is located at 103257 and 104207 bases of the gene cluster nucleotide sequence, has a length of 951 base pairs, encodes a transcription regulatory factor, and has a length of 316 amino acids.
Figure BDA0000889460040000476
Figure BDA0000889460040000481
According to an embodiment of the invention, the 3T1 gene encodes SEQ ID NO: 31, as shown below. According to an embodiment of the invention, the 3T1 gene is located in the Streptomyces strain SEQ ID NO: 36, the length of the gene sequence fragment is 1365 base pairs, and the gene sequence fragment encodes membrane integrated transfer protein and has the length of 454 amino acids.
Figure BDA0000889460040000482
According to an embodiment of the invention, the 3T2 gene encodes SEQ ID NO: 32, as shown below. According to an embodiment of the invention, the 3T2 gene is located in the Streptomyces strain SEQ ID NO: 36, the length of 687 base pairs, codes ABC transfer factor, and the length is 228 amino acids.
Figure BDA0000889460040000483
According to an embodiment of the invention, the 3T3 gene encodes SEQ ID NO: 33, as shown below. According to the embodiment of the invention, 3T3 is located at 1 st to 609 nd bases of a gene cluster nucleotide sequence, is 609 base pairs in length, encodes a two-component feedback regulator and is 202 amino acids in length.
Figure BDA0000889460040000484
According to an embodiment of the invention, the 3T4 gene encodes SEQ ID NO: 34, as shown below. According to the embodiment of the invention, 3T4 is located at 1714 bases 515-th of the gene cluster nucleotide sequence, is 1200 base pairs long, codes a chemoreceptor and is 399 amino acids long.
Figure BDA0000889460040000485
According to an embodiment of the invention, the 3T5 gene encodes SEQ ID NO: 35, as shown below. According to the embodiment of the present invention, 3T5 is located at base 1707-2903 of the gene cluster nucleotide sequence and is 1197 base pairs in length, encodes a two-component sensor histidine kinase and is 398 amino acids in length.
Figure BDA0000889460040000486
Referring to fig. 1, along the 5 '-3' end of the genes, 3T3 gene, 3T4 gene, 3T5 gene, 3R1 gene, 3R2 gene, 3a1 gene, 3a2 gene, 3A3 gene, 3a4 gene, 3A5 gene, 3A6 gene, 3P1 gene, 3G5 gene, 3M gene, 3G4 gene, 3G1 gene, 3G9 gene, 3a7 gene, 3E gene, 3a10 gene, 3O gene, 3I gene, 3P2 gene, 3a9 gene, 3a11 gene, 3A8 gene, 3P3 gene, 3R4 gene, 3G6 gene, 3G7 gene, 3G8 gene, 3T1 gene, and 3T2 gene were sequentially connected in series according to the present invention.
In the present invention, "tandem" merely indicates the order of connection of genes, and adjacent genes may be directly connected to each other, or other gene fragments may be present or partial sequences of the connection sites may overlap with each other.
According to some embodiments of the invention, the 3T3 gene, 3T5 gene, 3a1 gene, 3a2 gene, 3A3 gene, 3a4 gene, 3a5 gene, 3a6 gene, 3P1 gene, 3M gene, 3G4 gene, 3G3 gene, 3G9 gene, 3P2 gene, 3R4 gene, 3G7 gene, and 3T2 gene are expressed in the same direction.
According to some embodiments of the invention, the expression direction of the 3T4 gene, the 3R1 gene, the 3R2 gene, the 3G5 gene, the 3G2 gene, the 3G1 gene, the 3a7 gene, the 3E gene, the 3a10 gene, the 3O gene, the 3I gene, the 3a9 gene, the 3a11 gene, the 3a8 gene, the 3P3 gene, the 3G6 gene, the 3G8 gene, and the 3T1 gene is the same.
Microorganisms
According to another aspect of the present invention, there is provided a microorganism. According to an embodiment of the invention, the microorganism encodes the biosynthetic gene cluster described above. The inventors have surprisingly found that the J1001-3 compound can be synthesized efficiently, simply and at low cost by performing a fermentation treatment using the microorganism.
According to an embodiment of the invention, the microorganism is streptomyces. According to a particular embodiment of the invention, the microorganism is Streptomyces endomyces subtype Streptomyces.
According to yet another aspect of the present invention, there is provided a process for preparing a compound of J1001-3. Referring to fig. 2, the method is explained according to an embodiment of the present invention, the method including:
s100 fermentation treatment
According to an embodiment of the present invention, the fermentation treatment is performed using the aforementioned microorganism to obtain a fermented microorganism.
According to a specific embodiment of the invention, the fermentation medium conditions are: soluble starch (30g/L), soybean cake powder (10g/L), yeast extract (2.5g/L) and calcium carbonate (3 g/L). Therefore, the fermentation effect is good, and the yield of the J1001-3 compound is high.
According to a particular embodiment of the invention, the fermentation treatment is carried out for a period of 7 to 8 days.
S200 wall breaking treatment
According to the embodiment of the invention, the fermented microorganism is subjected to wall breaking treatment to obtain a solution containing the J1001-3 compound.
S300 purification
According to an embodiment of the present invention, the J1001-3 compound is purified from a solution containing the J1001-3 compound to obtain the J1001-3 compound.
According to some embodiments of the invention, the solution containing the compound J1001-3 is spin dried, extracted with ethyl acetate, concentrated, and then separated by silica gel column and further purified by semi-preparative HPLC to give the desired product.
According to the method for producing the J1001-3 compound of the embodiment of the present invention, the J1001-3 compound can be efficiently synthesized by performing the fermentation treatment using the aforementioned microorganism. Then, the pure J1001-3 compound can be obtained efficiently, simply and at low cost through microbial wall breaking treatment and separation and purification treatment.
According to some embodiments of the invention, the biosynthetic pathway of the J1001-3 compound is predicted from genetic predictions as shown in fig. 3. On one hand, long-chain fatty acid chains are finally formed by catalyzing the extension synthesis of propionyl coenzyme A and methylmalonyl coenzyme A by a polyketide synthesis gene cluster, and an intermediate product of J1001-3 is obtained by modification of 3O,3I and 3E genes, on the other hand, glycosyl is obtained by catalysis of genes such as 3G1,3G2,3G3,3G4 and 3M, and then is transferred onto the fatty acid chains by glycosyltransferases 3G5,3G6,3G7 and 3G9, and finally J1001-3 is formed by the action of P450 enzymes 3P1,3P2 and 3P 3.
The present invention is described below with reference to specific examples, which are intended to be illustrative only and are not to be construed as limiting the invention.
The scheme of the invention will be explained with reference to the examples. It will be appreciated by those skilled in the art that the following examples are illustrative of the invention only and should not be taken as limiting the scope of the invention. The examples do not specify particular techniques or conditions, and are carried out according to techniques or conditions described in literature in the art (for example, refer to molecular cloning, a laboratory Manual, third edition, scientific Press, written by J. SammBruke et al, Huang Petang et al) or according to product instructions. The reagents or apparatus used are conventional products which are not indicated by the manufacturer and are commercially available, for example from sigma.
Example 1
Streptomyces endomyces subtype Streptomyces is inoculated to an SFM plate and cultured for about three days to four days. When colonies are formed in the SFM culture medium, selecting single colonies to a seed culture medium for culture for about three days to four days, inoculating the single colonies to a fermentation culture medium according to the amount of 1 percent (the components of the fermentation culture medium are 30g/L of soluble starch, 10g/L of soybean cake powder, 2.5g/L of yeast extract, CaCO 3 3g/L, pH 7.2). The culture conditions are as follows: 30 ℃ and 220 rpm, and culturing for 7 to 8 days.
And when the culture is carried out for 7 th or 8 th day, collecting fermentation liquor, separating the supernatant from the mycelium by high-speed centrifugation, adding the same amount of acetone into the mycelium to break the bacteria, carrying out ultrasonic treatment for 20min, carrying out rotary evaporation on the acetone, extracting the supernatant and the mycelium by using the same amount of ethyl acetate, and repeating the steps once. Concentrating to dryness by rotary evaporation, then carrying out crude separation by using a silica gel column to obtain a crude product detected by using HPLC, and considering that the HPLC result shows that the yield of the strain is higher, carrying out TLC plate spotting on a concentrated sample, developing in an iodine cylinder, removing a very obvious point, dissolving by using methanol, carrying out high-speed centrifugation, taking a supernatant, and carrying out mass spectrometry to determine the position of a target point, wherein the result is shown in figure 4, and the compound is a J1001-3 compound.
Example 2
The sequence information of the biosynthetic gene cluster of the J1001-3 compound is researched by taking Streptomyces endous subtype Streptomyces as a research object, and the specific method comprises the following steps:
1. extraction of DNA
(1) Streptomyces endomyces subtype Streptomyces is inoculated into TSBY culture medium and cultured for 2 days, and then thallus is collected at 7000rpm × 5 min.
(2) The collected cells were discarded from the supernatant, and 30ml of SET buffer was added thereto, and the mixture was dispersed and centrifuged at 7000rpm for 5 minutes. The supernatant was discarded again, 10ml of SET buffer was added, the cells were disrupted, 300. mu.l of lysozyme (100mg/ml) was added, and the mixture was subjected to 37 ℃ water bath for 30 to 60 minutes, 100. mu.l of proteinase K (100mg/ml), 10. mu.l of RNase (10mg/ml) and 37 ℃ water bath for 30 minutes.
(3) To the mixture obtained in step (2), 1.2ml of 10% SDS was added, and the mixture was incubated at 55 ℃ for 2 hours while shaking gently every 15 minutes until the liquid became clear.
(4) 4ml of 5M NaCl was added to the liquid obtained in step (3), mixed well and cooled to 37 ℃. 10ml of chloroform was added, gently mixed for 30 minutes, and centrifuged at 12000rpm for 15 minutes.
(5) And (4) adding 10ml of chloroform into the centrifuged supernatant in the step (4), gently mixing for 30 minutes, and centrifuging at 12000rpm for 15 minutes.
(6) And (4) taking the supernatant centrifuged in the step (5), adding 0.8-time volume of isopropanol, and gently swirling until filamentous DNA appears.
(7) And (3) picking out the DNA in an EP tube, adding 70% ethanol for washing, then pouring out the ethanol, naturally drying, dissolving in a certain amount of double distilled water, and extracting to obtain the DNA of the streptomycete.
2. DNA sequence analysis
The genome was sent to a sequencing company to perform genome sequencing to obtain genome information, and the assembled genome was predicted for the gene encoding the protein using GeneMarkS. Then, an anti SMASH software is utilized to predict a region similar to a J1-001 compound synthetic gene cluster, and a J1001-3 synthetic related gene is excavated by combining the comparison result of proteins in the J1-001 compound synthetic gene cluster in the bacterial coding gene data set. The structure of the gene cluster is shown in FIG. 2, and is responsible for the biosynthesis of compound J1001-3, and the functional analysis of each gene is shown in Table 1.
Figure BDA0000889460040000501
Figure BDA0000889460040000511
In the description of the specification, reference to the description of "one embodiment," "some embodiments," "an example," "a specific example," or "some examples" or the like means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above do not necessarily refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
While embodiments of the invention have been shown and described, it will be understood by those of ordinary skill in the art that: various changes, modifications, substitutions and alterations can be made to the embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the claims and their equivalents.
Figure IDA0000919950730000011
Figure IDA0000919950730000021
Figure IDA0000919950730000031
Figure IDA0000919950730000041
Figure IDA0000919950730000051
Figure IDA0000919950730000061
Figure IDA0000919950730000071
Figure IDA0000919950730000081
Figure IDA0000919950730000091
Figure IDA0000919950730000101
Figure IDA0000919950730000111
Figure IDA0000919950730000121
Figure IDA0000919950730000131
Figure IDA0000919950730000141
Figure IDA0000919950730000151
Figure IDA0000919950730000161
Figure IDA0000919950730000171
Figure IDA0000919950730000181
Figure IDA0000919950730000191
Figure IDA0000919950730000201
Figure IDA0000919950730000211
Figure IDA0000919950730000221
Figure IDA0000919950730000231
Figure IDA0000919950730000241
Figure IDA0000919950730000251
Figure IDA0000919950730000261
Figure IDA0000919950730000271
Figure IDA0000919950730000281
Figure IDA0000919950730000291
Figure IDA0000919950730000301
Figure IDA0000919950730000311
Figure IDA0000919950730000321
Figure IDA0000919950730000331
Figure IDA0000919950730000341
Figure IDA0000919950730000351
Figure IDA0000919950730000361
Figure IDA0000919950730000371
Figure IDA0000919950730000381
Figure IDA0000919950730000391
Figure IDA0000919950730000401
Figure IDA0000919950730000411
Figure IDA0000919950730000421
Figure IDA0000919950730000431
Figure IDA0000919950730000441
Figure IDA0000919950730000451
Figure IDA0000919950730000461
Figure IDA0000919950730000471
Figure IDA0000919950730000481
Figure IDA0000919950730000491
Figure IDA0000919950730000501
Figure IDA0000919950730000511
Figure IDA0000919950730000521
Figure IDA0000919950730000531
Figure IDA0000919950730000541
Figure IDA0000919950730000551
Figure IDA0000919950730000561
Figure IDA0000919950730000571
Figure IDA0000919950730000581
Figure IDA0000919950730000591
Figure IDA0000919950730000601
Figure IDA0000919950730000611
Figure IDA0000919950730000621
Figure IDA0000919950730000631
Figure IDA0000919950730000641
Figure IDA0000919950730000651
Figure IDA0000919950730000661
Figure IDA0000919950730000671
Figure IDA0000919950730000681
Figure IDA0000919950730000691
Figure IDA0000919950730000701
Figure IDA0000919950730000711
Figure IDA0000919950730000721
Figure IDA0000919950730000731
Figure IDA0000919950730000741
Figure IDA0000919950730000751
Figure IDA0000919950730000761
Figure IDA0000919950730000771
Figure IDA0000919950730000781
Figure IDA0000919950730000791
Figure IDA0000919950730000801
Figure IDA0000919950730000811
Figure IDA0000919950730000821
Figure IDA0000919950730000831
Figure IDA0000919950730000841
Figure IDA0000919950730000851
Figure IDA0000919950730000861
Figure IDA0000919950730000871
Figure IDA0000919950730000881
Figure IDA0000919950730000891
Figure IDA0000919950730000901
Figure IDA0000919950730000911
Figure IDA0000919950730000921
Figure IDA0000919950730000931
Figure IDA0000919950730000941
Figure IDA0000919950730000951
Figure IDA0000919950730000961
Figure IDA0000919950730000971
Figure IDA0000919950730000981
Figure IDA0000919950730000991
Figure IDA0000919950730001001
Figure IDA0000919950730001011
Figure IDA0000919950730001021
Figure IDA0000919950730001031
Figure IDA0000919950730001041
Figure IDA0000919950730001051
Figure IDA0000919950730001061
Figure IDA0000919950730001071
Figure IDA0000919950730001081
Figure IDA0000919950730001091
Figure IDA0000919950730001101
Figure IDA0000919950730001111
Figure IDA0000919950730001121
Figure IDA0000919950730001131
Figure IDA0000919950730001141
Figure IDA0000919950730001151
Figure IDA0000919950730001161
Figure IDA0000919950730001171
Figure IDA0000919950730001181
Figure IDA0000919950730001191
Figure IDA0000919950730001201
Figure IDA0000919950730001211
Figure IDA0000919950730001221
Figure IDA0000919950730001231
Figure IDA0000919950730001241
Figure IDA0000919950730001251
Figure IDA0000919950730001261
Figure IDA0000919950730001271
Figure IDA0000919950730001281
Figure IDA0000919950730001291
Figure IDA0000919950730001301
Figure IDA0000919950730001311
Figure IDA0000919950730001321
Figure IDA0000919950730001331
Figure IDA0000919950730001341
Figure IDA0000919950730001351
Figure IDA0000919950730001361
Figure IDA0000919950730001371
Figure IDA0000919950730001381
Figure IDA0000919950730001391
Figure IDA0000919950730001401
Figure IDA0000919950730001411
Figure IDA0000919950730001421
Figure IDA0000919950730001431
Figure IDA0000919950730001441
Figure IDA0000919950730001451
Figure IDA0000919950730001461
Figure IDA0000919950730001471
Figure IDA0000919950730001481
Figure IDA0000919950730001491
Figure IDA0000919950730001501
Figure IDA0000919950730001511
Figure IDA0000919950730001521
Figure IDA0000919950730001531
Figure IDA0000919950730001541
Figure IDA0000919950730001551
Figure IDA0000919950730001561
Figure IDA0000919950730001571
Figure IDA0000919950730001581
Figure IDA0000919950730001591
Figure IDA0000919950730001601
Figure IDA0000919950730001611
Figure IDA0000919950730001621
Figure IDA0000919950730001631
Figure IDA0000919950730001641
Figure IDA0000919950730001651
Figure IDA0000919950730001661
Figure IDA0000919950730001671
Figure IDA0000919950730001681
Figure IDA0000919950730001691
Figure IDA0000919950730001701
Figure IDA0000919950730001711
Figure IDA0000919950730001721
Figure IDA0000919950730001731
Figure IDA0000919950730001741
Figure IDA0000919950730001751
Figure IDA0000919950730001761
Figure IDA0000919950730001771
Figure IDA0000919950730001781
Figure IDA0000919950730001791
Figure IDA0000919950730001801
Figure IDA0000919950730001811
Figure IDA0000919950730001821
Figure IDA0000919950730001831
Figure IDA0000919950730001841
Figure IDA0000919950730001851
Figure IDA0000919950730001861
Figure IDA0000919950730001871
Figure IDA0000919950730001881
Figure IDA0000919950730001891
Figure IDA0000919950730001901
Figure IDA0000919950730001911
Figure IDA0000919950730001921
Figure IDA0000919950730001931
Figure IDA0000919950730001941
Figure IDA0000919950730001951
Figure IDA0000919950730001961
Figure IDA0000919950730001971
Figure IDA0000919950730001981
Figure IDA0000919950730001991
Figure IDA0000919950730002001
Figure IDA0000919950730002011
Figure IDA0000919950730002021
Figure IDA0000919950730002031
Figure IDA0000919950730002041
Figure IDA0000919950730002051
Figure IDA0000919950730002061
Figure IDA0000919950730002071
Figure IDA0000919950730002081
Figure IDA0000919950730002091
Figure IDA0000919950730002101
Figure IDA0000919950730002111
Figure IDA0000919950730002121
Figure IDA0000919950730002131
Figure IDA0000919950730002141
Figure IDA0000919950730002151
Figure IDA0000919950730002161
Figure IDA0000919950730002171
Figure IDA0000919950730002181
Figure IDA0000919950730002191
Figure IDA0000919950730002201
Figure IDA0000919950730002211
Figure IDA0000919950730002221
Figure IDA0000919950730002231
Figure IDA0000919950730002241
Figure IDA0000919950730002251

Claims (4)

1. A biosynthetic gene cluster of a compound, wherein the compound has the structure,
Figure FDA0003296179250000011
wherein the biosynthetic gene cluster comprises:
the I type linear polyketide synthase gene module comprises: 3A1 gene, 3A2 gene, 3A3 gene, 3A4 gene, 3A5 gene, 3A6 gene, 3A7 gene, 3A8 gene, 3A9 gene, 3A10 gene and 3A11 gene,
wherein, the 3A1 gene codes SEQ ID NO: 1;
the 3A2 gene encodes SEQ ID NO: 2;
the 3A3 gene encodes SEQ ID NO: 3;
the 3A4 gene encodes SEQ ID NO: 4;
the 3A5 gene encodes SEQ ID NO: 5;
the 3A6 gene encodes SEQ ID NO: 6;
the 3A7 gene encodes SEQ ID NO: 7;
the 3A8 gene encodes SEQ ID NO: 8;
the 3A9 gene encodes SEQ ID NO: 9;
the 3A10 gene encodes SEQ ID NO: 10;
the 3A11 gene encodes SEQ ID NO: 11;
a glycosyl synthesis-associated gene module comprising: 3G1 gene, 3G2 gene, 3G3 gene, 3G4 gene, 3G5 gene, 3G6 gene, 3G7 gene, 3G8 gene, 3M gene, and 3G9 gene; and
a modifier gene module comprising: 3O gene, 3I gene, 3E gene, 3P1 gene, 3P2 gene and 3P3 gene,
wherein the 3G1 gene encodes the amino acid sequence of SEQ ID NO: 12;
the 3G2 gene encodes SEQ ID NO: 13;
the 3G3 gene encodes SEQ ID NO: 14;
the 3G4 gene encodes SEQ ID NO: 15;
the 3G5 gene encodes SEQ ID NO: 16;
the 3G6 gene encodes SEQ ID NO: 17;
the 3G7 gene encodes SEQ ID NO: 18;
the 3G8 gene encodes SEQ ID NO: 19;
the 3M gene encodes SEQ ID NO: 20;
the 3G9 gene encodes SEQ ID NO: 21;
the 3O gene encodes SEQ ID NO: 22;
the 3I gene encodes SEQ ID NO: 23;
the 3E gene encodes SEQ ID NO: 24;
the 3P1 gene encodes SEQ ID NO: 25;
the 3P2 gene encodes SEQ ID NO: 26;
the 3P3 gene encodes SEQ ID NO: 27, or a pharmaceutically acceptable salt thereof.
2. The biosynthetic gene cluster of claim 1, further comprising:
a regulatory gene module comprising: 3R1 gene, 3R2 gene, 3R4 gene, 3T1 gene, 3T2 gene, 3T3 gene, 3T4 gene and 3T5 gene,
wherein, the 3R1 gene codes SEQ ID NO: 28;
the 3R2 gene encodes SEQ ID NO: 29;
the 3R4 gene encodes SEQ ID NO: 30;
the 3T1 gene encodes SEQ ID NO: 31;
the 3T2 gene encodes SEQ ID NO: 32;
the 3T3 gene encodes SEQ ID NO: 33;
the 3T4 gene encodes SEQ ID NO: 34;
the 3T5 gene encodes SEQ ID NO: 35.
3. The biosynthetic gene cluster of claim 2, wherein along the 5 '-3' end of a gene the 3T3 gene, the 3T4 gene, the 3T5 gene, the 3R1 gene, the 3R2 gene, the 3A1 gene, the 3A2 gene, the 3A3 gene, the 3A4 gene, the 3A5 gene, the 3A6 gene, the 3P1 gene, the 3G5 gene, the 3M gene, the 3G4 gene, the 3G1 gene, the 3G9 gene, the 3A7 gene, the 3E gene, the 3A10 gene, the 3O gene, the 3I gene, the 3P2 gene, the 3A9 gene, the 3A11 gene, the 3A8 gene, the 3P3 gene, the 3R4 gene, the 3G6 gene, the 3G7 gene, the 3G8 gene, the 3G4 gene, the 3A2 gene, the 3A11 gene, the 3A9 gene, the 3A4 gene, the 3G4 gene, and the like, The 3T1 gene and the 3T2 gene are sequentially connected in series.
4. The biosynthetic gene cluster of any of claims 1 to 3, wherein the nucleotide sequence of the biosynthetic gene cluster is as set forth in SEQ ID NO: shown at 36.
CN201511000174.9A 2015-12-24 2015-12-24 Biosynthetic gene cluster of compounds and application thereof Active CN106916836B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201511000174.9A CN106916836B (en) 2015-12-24 2015-12-24 Biosynthetic gene cluster of compounds and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201511000174.9A CN106916836B (en) 2015-12-24 2015-12-24 Biosynthetic gene cluster of compounds and application thereof

Publications (2)

Publication Number Publication Date
CN106916836A CN106916836A (en) 2017-07-04
CN106916836B true CN106916836B (en) 2022-08-12

Family

ID=59454935

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201511000174.9A Active CN106916836B (en) 2015-12-24 2015-12-24 Biosynthetic gene cluster of compounds and application thereof

Country Status (1)

Country Link
CN (1) CN106916836B (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106916836B (en) * 2015-12-24 2022-08-12 武汉合生科技有限公司 Biosynthetic gene cluster of compounds and application thereof
CN112442507B (en) * 2019-09-05 2022-09-30 武汉合生科技有限公司 Biosynthetic gene cluster of maduramicin compound and application thereof

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1316002A (en) * 1998-07-06 2001-10-03 拜奥蒂卡技术有限公司 Polyketides, their preparation, and materials for use therein
CN1676607A (en) * 2003-05-16 2005-10-05 惠氏公司 Cloning genes from streptomyces cyaneogriseus subsp. noncyanogenus for biosynthesis of antibiotics and methods of use
US8148102B2 (en) * 2007-02-08 2012-04-03 Uwm Research Foundation, Inc. Sequences for FK228 biosynthesis and methods of synthesizing FK228 and FK228 analogs
CN103131716A (en) * 2011-12-02 2013-06-05 上海交通大学 Biosynthetic gene cluster of salinomycin and application thereof
US8664186B2 (en) * 2009-07-24 2014-03-04 Universite De Lorraine Stambomycin and derivatives, their production and their uses as drugs
CN103820474A (en) * 2012-11-16 2014-05-28 中国医药集团总公司四川抗菌素工业研究所 Biosynthesis gene cluster of polyenoid and polyol macrolide compound
CN106916836A (en) * 2015-12-24 2017-07-04 武汉臻智生物科技有限公司 The biological synthesis gene cluster of compound and its application

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6495348B1 (en) * 1993-10-07 2002-12-17 Regents Of The University Of Minnesota Mitomycin biosynthetic gene cluster
US6902913B2 (en) * 1997-04-30 2005-06-07 Kosan Biosciences, Inc. Recombinant narbonolide polyketide synthase
EP1572966B1 (en) * 2002-10-18 2014-04-16 University of Florida Complete biosynthetic gene set for synthesis of polyketide antibiotics, including the albicidin family, resistance genes and uses thereof
GB0230217D0 (en) * 2002-12-27 2003-02-05 Biotica Tech Ltd Borrelidin-producing polyketide synthase and its uses
US7507752B2 (en) * 2004-06-03 2009-03-24 Wyeth Biosynthetic gene cluster for the production of a complex polyketide
US20100022766A1 (en) * 2008-07-25 2010-01-28 Wyeth Biosynthetic gene cluster for the production of a complex polyketide

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1316002A (en) * 1998-07-06 2001-10-03 拜奥蒂卡技术有限公司 Polyketides, their preparation, and materials for use therein
CN1676607A (en) * 2003-05-16 2005-10-05 惠氏公司 Cloning genes from streptomyces cyaneogriseus subsp. noncyanogenus for biosynthesis of antibiotics and methods of use
US8148102B2 (en) * 2007-02-08 2012-04-03 Uwm Research Foundation, Inc. Sequences for FK228 biosynthesis and methods of synthesizing FK228 and FK228 analogs
US8664186B2 (en) * 2009-07-24 2014-03-04 Universite De Lorraine Stambomycin and derivatives, their production and their uses as drugs
CN103131716A (en) * 2011-12-02 2013-06-05 上海交通大学 Biosynthetic gene cluster of salinomycin and application thereof
CN103820474A (en) * 2012-11-16 2014-05-28 中国医药集团总公司四川抗菌素工业研究所 Biosynthesis gene cluster of polyenoid and polyol macrolide compound
CN106916836A (en) * 2015-12-24 2017-07-04 武汉臻智生物科技有限公司 The biological synthesis gene cluster of compound and its application

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
A second type-I PKS gene cluster isolated from Streptomyces hygroscopicus ATCC 29253, a rapamycin-producing strain;Xiaoan Ruan 等;《Gene》;19971205;第1–9页 *
glucose-1-phosphate thymidylyltransferase RfbA [Streptomyces sparsogenes];NCBI;《Genbank Databse》;20191226;Accession No.WP_065957879.1 *
Heterologous Expression of a Cryptic Giant Type I PKS Gene Cluster Leads to the Production of Ansaseomycin;Shuang He Liu 等;《Org. Lett.》;20190429;第3785-3788页 *
MULTISPECIES: AfsR/SARP family transcriptional regulator [Streptomyces];NCBI;《Genbank Database》;20181007;Accession No.WP_014180989.1 *
type I polyketide synthase [Streptomyces milbemycinicus];NCBI;《Genbank Database》;20180522;Accession No.WP_086859474.1 *
type I polyketide synthase [Streptomyces sp. NBS 14/10];NCBI;《Genbank DataBASE》;20180522;Accession No.WP_089509396.1 *
南昌链霉菌中聚醚抗生素释放机制的研究;刘天罡;《中国优秀博士学位论文全文数据库(电子期刊)》;20080201;全文 *
抗生素FR-008生物合成基因簇部分功能区域的分析;何璟;《中国优秀硕士学位论文全文数据库(电子期刊)》;20010524;全文 *
链霉菌基因组中DNA大片段的基因置换与克隆;白林泉;《中国优秀博士学位论文全文数据库(电子期刊)》;19990601;全文 *

Also Published As

Publication number Publication date
CN106916836A (en) 2017-07-04

Similar Documents

Publication Publication Date Title
CN107164253B (en) Genetically engineered bacterium for catalyzing glucosidation of flavonoid compound and application thereof
RU2719189C2 (en) Biosynthetic gene cluster of carrimycin
CN103060248A (en) Method for constructing gene engineering FK506 high-producing strain and streptomyces tsukubaensis high-producing strain
CN104357418A (en) Applications of glycosyltransferase and mutants thereof to synthesis of ginsenoside Rh2
CN106916836B (en) Biosynthetic gene cluster of compounds and application thereof
CN1687403A (en) Engineering bacterium of producing ivermectin, its constructing method and application
CN101802168A (en) Method for production of non-natural antibiotic
CN105176899A (en) Method for constructing recombinant strain capable of producing target gene product at high yield, and recombinant strain and application thereof
CN106636141B (en) A kind of biological synthesis gene cluster of Luo Bolu ketone and its application
CN106916835B (en) Biosynthetic gene cluster of compounds and application thereof
CN106916834B (en) Biosynthetic gene cluster of compounds and application thereof
CN107629994A (en) A kind of method and streptomyces hygroscopicus superior strain of structure FK520 high-yielding engineering bacterial strains
CN111378008A (en) Lipopeptide compound Totopotecamides, and preparation method and application thereof
CN105002106B (en) The high-yielding engineering bacterial strain of plate mycin peace laminin and its fermentation and separation purifying technique
CN112625925B (en) High-yield strain of dalbavancin precursor A40926B0 and application thereof
CN105861455B (en) DoxA protein mutants and its encoding gene and application
CN106190854B (en) A kind of preparation method of desert pseudocyst bacterium and oritavancin intermediate
CN103820362A (en) Construction of biosynthesis gentamicin X2 engineering bacteria and application thereof
CN110423790A (en) A kind of metabolic engineering method of antimycotic tetramycin B orientation high yield
CN112430608B (en) Method for constructing high-yield engineering bacteria of oritavancin precursor and application
KR100636653B1 (en) Novel Olivosyl Pikromycin Derivatives and Method for Preparing the Same
CN106906192A (en) Glucosyltransferase and application thereof in synthesis of crocetin glucose ester
CN116144637A (en) Rumex olivaceus histone deacetylase and encoding gene and application thereof
KR100649394B1 (en) Novel Olivosyl Methymycin Derivatives and Method for Preparing the Same
CN108456689A (en) The method for improving ansamitocin P-3 biosynthesis yield

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
TA01 Transfer of patent application right
TA01 Transfer of patent application right

Effective date of registration: 20220718

Address after: 430075 room d102, building B5, building b4-b8, Wuhan National Biological Industry (Jiufeng innovation) base, No. 666, Gaoxin Avenue, East Lake New Technology Development Zone, Wuhan, Hubei

Applicant after: Wuhan Hesheng Technology Co.,Ltd.

Address before: Building B5, R & D building, Wuhan Institute of biotechnology, 666 Gaoxin Avenue, Donghu Development Zone, Wuhan City, Hubei Province, 430075

Applicant before: WUHAN J1 BIOTECH Co.,Ltd.

GR01 Patent grant
GR01 Patent grant