Biosynthesis of lovastatin and related metabolites formed by fungal iterative PKS enzymes

The fungal polyketide lovastatin is a cholesterol lowering agent that is an immediate precursor to a multi‐billion dollar drug, simvastatin (Zocor™). Lovastatin is produced by an iterative type I polyketide synthase known as LovB and a partner enoyl reductase (LovC). There is evidence that a Diels‐A...

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Veröffentlicht in:	Biopolymers 2010-09, Vol.93 (9), p.755-763
Hauptverfasser:	Campbell, Chantel D., Vederas, John C.
Format:	Artikel
Sprache:	eng
Schlagworte:	biosynthesis Cytochalasins - biosynthesis Cytochalasins - chemistry Diels Alderase enzyme Lactones - chemistry Lactones - metabolism Lovastatin - analogs & derivatives Lovastatin - biosynthesis Lovastatin - chemistry natural product polyketide Polyketide Synthases - metabolism Pyrrolidinones - chemistry Pyrrolidinones - metabolism RNA, Catalytic - metabolism Simvastatin - chemical synthesis Simvastatin - chemistry Tetrahydronaphthalenes - chemistry Tetrahydronaphthalenes - metabolism
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Beschreibung
Zusammenfassung:	The fungal polyketide lovastatin is a cholesterol lowering agent that is an immediate precursor to a multi‐billion dollar drug, simvastatin (Zocor™). Lovastatin is produced by an iterative type I polyketide synthase known as LovB and a partner enoyl reductase (LovC). There is evidence that a Diels‐Alderase enzyme activity is utilized in its biosynthesis. This review examines the biosynthesis of lovastatin, as well as of compactin, equisetin, cytochalasins, and solanapyrones, which are other structurally related polyketides that appear to utilize a Diels‐Alderase. © 2010 Wiley Periodicals, Inc. Biopolymers 93: 755–763, 2010.
ISSN:	0006-3525 1097-0282
DOI:	10.1002/bip.21428