Methods for producing ML-236B, a pravastatin precursor,...

Details Methods for producing ML-236B, a pravastatin precursor,... Methods for producing ML-236B, a pravastatin precursor,...

2006-06-06

2006-06-06

Kerr, Kathleen (Department: 1652)

Chemistry: molecular biology and microbiology

Micro-organism, tissue cell culture or enzyme using process...

Preparing oxygen-containing organic compound

Reexamination Certificate

active

07056710

ABSTRACT:
Polynucleotides, such as DNA, are provided which accelerate the biosynthesis of a HMG-CoA reductase inhibitor, ML-236B, in an ML-236B producing micro-organism when introduced in the ML-236B producing micro-organism. Pravastatin, which is an HM-CoA reductase inhibitor, can be obtained usingStreptomyces carbophilusby microbial conversion of ML-236B produced byPencillium citrinum. The polynucleotides encode a gene (such as micA (polyketide synthase), mlcB (polyketide synthase), micE (efflux pump) or mlcR (transcription factor). Provided are vectors into which such polynucleotides are incorporated; host cells transformed by such vectors; and proteins expressed by such vectors. A method for producing ML-236B using such polynucleotides and/or proteins which comprises recovering ML-236B from a culture of the host cell.

REFERENCES:
patent: 5179013 (1993-01-01), Matsuoka et al.
patent: 57-2240 (1982-01-01), None
patent: WO 95/12661 (1995-05-01), None
patent: WO 00/37629 (2000-06-01), None
patent: WO 01/12814 (2001-02-01), None
Abe et al. Molecular cloning and characterization of an ML-236B (compactin) biosynthetic gene cluster inPenicillium citrinum. Mol Genet Genomics Jul. 2002;267(5):636-46.
Abe et al. Effect of increased dosage of the ML-236B (compactin) biosynthetic gene cluster on ML-236B production inPenicillium citrinum. Mol Genet Genomics Sep. 2002;268(1):130-7.
Abe et al. Functional analysis of mlcR, a regulatory gene for ML-236B (compactin) biosynthesis inPenicillium citrinum. Mol Genet Genomics Nov. 2002;268(3):352-61.
Yu et al. Comparative Mapping of Aflatoxin Pathway Gene Clusters inAspergillus parasiticusandAspergillus flavus. Applied and Environmental Microbiology (1995) 61 (6): 2365-2371.
Chang et al. Increased Expression ofAspergillus parasiticusaflR, Encoding a Sequence-Specific DNA-Binding Protein, Relieves Nitrate Inhibition of Aflatoxin Biosynthesis. Applied and Environmental Microbiology (1995) 61 (6): 2372-2377.
J. Kennedy et al., Database EMBL 'Online!, Nov. 1, 1999 retrieved from EBI, Database accession No. Q9Y7C8 XP002184089.
J. Kennedy et al., Database EMBL 'Online!, Jun. 3, 1999 retrieved from EBI, Database accession No. AF141925 XP002184086.
J. Kennedy et al., Database EMBL 'Online!, Nov. 1, 1999 retrieved from EBI, Database accession No. Q9Y7D5 XP002184087.
J. Kennedy et al., Database EMBL 'Online!, Jun. 3, 1999 retrieved from EBI, Database accession No. AF141924 XP002184129.
J. Kennedy et al., Database EMBL 'Online!, Nov. 1, 1999 retrieved from EBI, Database accession No. Q9Y7D3 XP002184088.
Akira Endo et al., ML-236A, ML-236B, and ML-236C, “New Inhibitors of Cholesterogenesis Produced ByPenicillum citrinum”, The Journal of Antibiotics, 29, 1346-1348 (1976).
Richard Moore et al., “Biosynthesis of the Hypocholesterolemic Agent Mevinolin ByAspergillus terreus. Determination of the Origin of Carbon, Hydrogen, and Oxygen Atoms by13C NMR and Mass Spectrometry”,J. Am. Chem. Soc., 107, 3694-3701 (1985).
David A. Hopwood and David H. Sherman, “Molecular Genetics of Polyketides and its Comparison to Fatty Acid Biosynthesis”,Annu. Rev. Genet., 24, 37-66 (1990).
C. Richard Hutchinson and Isao Fujii, “Polyketide Synthase Gene Manipulation: A Structure-Function Approach in Engineering Novel Antibiotics”,Annu. Rev. Microbiol., 49, 201-238 (1995).
Guo Hong Feng and Thomas J. Leonard, “Characterization of the Polyketide Synthase Gene (pksL1) Required for Aflatoxin Biosynthesis inAspergillus parasiticus”, Journal of Bacteriology, 177, 6246-6254 (1995).
Yoshitaka Takano et al., “Structural Analysis of PKS1, a Polyketide Synthase Gene Involved in Melanin Biosynthesis inColletotrichum lagenarium”, Mol. Gen. Genet., 249, 162-167 (1995).
Jiujiang Yu et al., “Comparative Mapping of Aflatoxin Pathway Gene Clusters inAspergillus parasiticusandAspergillus flavus”, Applied and Environmental Microbiology, 61, 2365-2371 (1995).
D. W. Brown et al., “Twenty-five Coregulated Transcripts Define a Sterigmatocystin Gene Cluster inAspergillus nidulans”, Proc. Natl. Acad. Sci. USA, 93, 1418-1422 (1996).
Jonathan Kennedy et al., “Modulation of Polyketide Synthase Activity by Accessory Proteins During Lovastatin Biosynthesis”,Science, 284, 1368-1372 (1999).
Lee Hendrickson et al., “Lovastatin Biosynthesis inAspergillus terreus: Characterization of Blocked Mutants, Enzyme Activities and a Multifuctional Polyketide Synthase Gene”,Chem. Biol., 6(7) , 429-439 (1999).
Nobufusa Serizawa, “Development of Two-step Fermentation-based Production of Pravastatin, an HMG-CoA Reductase”,J. Synthe. Organ. Chem., 55(4) , 334-338 (1997), Non-english.
I. Fujii, “Cloning of Polyketide Antibiotics Biosynthesising Genes”,Mochida Kinen Zaidan Kenku Seika Hokokusha, 5, 256-257 (1989).
Isao Fujii et al., “Structures and Functional Analyses of Fungal Polyketide Synthase Genes”,Actinomycetol, 12(1), 1-14 (1998).
Joachim Beck et al., “The Multifunctional 6-methylsalicylic Acid Synthase Gene ofPenicillium patulum”, Eur. J. Biochem., 192, (2), 487-498 (1990).
Yoshio Tsujita, “Discovery and Development of Hypolipidemic Drug, Pravastatin Sodium”,Tiss. Cult. Res. Commun., 12(4), 279-289, (1993).
C. Richard Hutchinson et al., “Aspects of the Biosynthesis of non-aromatic Fungal Polyketides by Iterative Polyketide Synthases”,Antonie van Leeuwenhoek, 78(3-4), 287-295, (2000).
Jonathan Kennedy et al., “Hypothetical 57.6 kDa Protein”, DATABASE EMBL, Online, Nov. 1, 1999, retrieved from EBI, accession No. Q9Y7D4.
Futoshi Nara et al., “Development of a Transformation System for the Filamentous, MLO-236B (compactin) -Producing FungusPenicillium citrinum”, Current Genetics, vol. 23, No. 1, 1993, pp. 28-32, XP001018104.
Masahiko Hosobuchi. et al., “Production of ML-236B, and Inhibitor of 3-Hydroxy-3-Methylglutaryl CoA Reductase byPenicillium citrinum: Improvements of Strain and Culture Conditions”,Bioscience Biotechnology Biochemistry, Japan Soc. For Bioscience, Biotechnology and Agrochem., Tokyo, Japan, vol. 57, No. 9, 1993, pp. 1414-1419.
Tatsuji Matsuoka et al., “Purification and Characterization of Cytochome P-450scafromStreptomyces carbophilus”, Eur. J. Biochem., 184, 707-713 (1989).
Ming-Shi Shiao and Hsiao-Shek Don, “Biosynthesis of Mevinolin, A Hypocholesterolemic Fungal Metabolite, inAspergillus terreus”, Proc. Natl. Sci. Counc. Repub. China B. ROC, 11, 223-231 (1987).
J. E. Flaherty and G. A. Payne; “Overexpression of aflR Leads to Upregulation of Pathway Gene Transcription and Increased Aflatoxin Production inAspergillus flavus”, Applied and Environmental Microbiology, Oct. 1997, pp. 3395-4000, vol. 63, No. 10.
Solveig Woitek et al., “3-Hydroxy-3-methylglutaryl-CoA reductase gene ofGibberella fujikuroi: isolation and characterization”,Current Genetics, vol. 31, No. 1, 1997, pp. 38-47.

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