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Title:
POLYKETIDE SYNTHASE ENZYMES AND RECOMBINANT DNA CONSTRUCTS THEREFOR
Document Type and Number:
WIPO Patent Application WO2000020601
Kind Code:
A3
Abstract:
Host cells comprising recombinant vectors encoding the FK-520 polyketide synthase and FK-520 modification enzymes can be used to produce the FK-520 polyketide. Recombinant DNA constructs comprising one or more FK-520 polyketide synthase domains, modules, open reading frames, and variants thereof can be used to produce recombinant polyketide synthases and a variety of different polyketides with application as pharmaceutical and veterinary products.

Inventors:
REEVES CHRISTOPHER (US)
CHU DANIEL (US)
KHOSLA CHAITAN (US)
SANTI DANIEL (US)
WU KAI (US)
Application Number:
PCT/US1999/022886
Publication Date:
October 26, 2000
Filing Date:
October 01, 1999
Export Citation:
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Assignee:
KOSAN BIOSCIENCES INC (US)
REEVES CHRISTOPHER (US)
CHU DANIEL (US)
KHOSLA CHAITAN (US)
SANTI DANIEL (US)
WU KAI (US)
International Classes:
A61K31/436; A61P25/00; A61P37/06; C07D498/18; C12N1/15; C12N1/19; C12N1/21; C12N5/10; C12N9/00; C12N9/10; C12N9/12; C12N15/09; C12N15/52; C12P17/18; C12P19/32; C12P19/62; (IPC1-7): C12N15/52; C12N15/54; C12N15/62; C12N9/10; C12P17/18; C12P19/32; C07D498/18
Foreign References:
EP0323042A11989-07-05
EP0356399A21990-02-28
EP0463690A11992-01-02
Other References:
MOTAMEDI H ET AL.: "The biosynthetic gene cluster for the macrolactone ring of the immunosuppressant FK506", EUR. J. BIOCHEM., vol. 256, no. 3, 15 September 1998 (1998-09-15), pages 528 - 534, XP000906738
STASSI D L ET AL.: "Ethyl-substituted erythromycin derivatives produced by directed metabolic engineering", PROC. NATL. ACAD. SCI. USA, vol. 95, no. 13, 23 June 1998 (1998-06-23), pages 7305 - 7309, XP002143632
REYNOLDS K A ET AL.: "Rapamycin, FK506, and ascomycin -related compounds", DRUGS PHARM. SCI., vol. 82, 1997, pages 497 - 520, XP000906777
DUMONT F J ET AL.: "The immunosuppressive and toxic effects of FK-506 are mechanistically related: pharmacology of a novel antagonist of FK-506 and rapamycin", JOURNAL OF EXPERIMENTAL MEDICINE, vol. 176, no. 3, 1 September 1992 (1992-09-01), pages 751 - 760, XP000906781
KAWAI M ET AL.: "Structure-activity profiles of macrolactam immunosuppressant FK-506 analogues", FEBS LETTERS, vol. 316, no. 2, January 1993 (1993-01-01), pages 107 - 113, XP002143633
MOTAMEDI H ET AL.: "Characterization of methyltransferase and hydroxylase genes involved in the biosynthesis of the immunosupressants FK506 and FK520", J. BACTERIOLOGY, vol. 178, no. 17, July 1996 (1996-07-01), pages 5243 - 5248, XP002137077
MOTAMEDI H ET AL.: "Structural organization of a multifunctional polyketide synthase involved in the biosynthesis of the macrolide immunosuppressant FK506", EUR. J. BIOCHEM., vol. 244, no. 1, 15 February 1997 (1997-02-15), pages 74 - 80, XP000906743
CHEN T S ET AL.: "Microbial transformation of immunosuppressive compounds. II. Specific desmethylation of 13-methoxy group of FK 506 and FR 9500520 by Actinomycete sp. ATCC 53828", J. ANTIBIOT., vol. 45, no. 4, April 1992 (1992-04-01), pages 577 - 580, XP002143634
SHAFIEE A ET AL.: "Enzymatic synthesis and immunosuppressive activity of novel desmethylated immunomycins (ascomycins)", J. ANTIBIOT., vol. 46, no. 9, September 1993 (1993-09-01), pages 1397 - 1405, XP002143635
KHOSLA C: "Harnessing the biosynthetic potential of modular polyketide synthases", CHEMICAL REVIEWS, vol. 97, no. 7, 1997, pages 2577 - 2590, XP002130646, ISSN: 0009-2665
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