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-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.
Campbell
Chantel D
CD
Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2.
Vederas
John C
JC
D003572:Cytochalasins / Q000096:biosynthesis / Q000737:chemistry; D007783:Lactones / Q000737:chemistry / Q000378:metabolism; D008148:Lovastatin / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000737:chemistry; D048630:Polyketide Synthases / Q000378:metabolism*; D011760:Pyrrolidinones / Q000737:chemistry / Q000378:metabolism; D016337:RNA, Catalytic / Q000378:metabolism*; D019821:Simvastatin / Q000138:chemical synthesis / Q000737:chemistry; D013764:Tetrahydronaphthalenes / Q000737:chemistry / Q000378:metabolism
D003572:Cytochalasins; C518747:Diels-Alder ribozyme; D007783:Lactones; D011760:Pyrrolidinones; D016337:RNA, Catalytic; D013764:Tetrahydronaphthalenes; C012258:mevastatin; C024509:equisetin; D048630:Polyketide Synthases; D008148:Lovastatin; D019821:Simvastatin