Recent advances in the biosynthetic studies of lovastatin.
The fungal metabolite lovastatin and its derivatives are widely prescribed cholesterol-lowering drugs that act as potent inhibitors of (3S)-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMG-CoA reductase). These drugs and a number of analogs that have been approved for use in humans are manufactured by fermentation in combination with subsequent chemical or microbial modification. This review highlights early work done in the elucidation of lovastatin biosynthesis involving the use of labeled precursors and the incubation of putative intermediates with cell-free extracts from various fungal sources. A series of more contemporary papers are also reviewed, describing the use of gene cloning to identify the various functions of the enzymes involved in the biosynthesis of lovastatin. In particular, overexpression, purification and the subsequent investigation of the various roles of lovastatin nonaketide synthase (LNKS) during lovastatin biosynthesis are discussed.
Sutherland
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Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada.
Auclair
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Vederas
J C
JC
D000818:Animals; D000924:Anticholesteremic Agents / Q000138:chemical synthesis*; D003001:Cloning, Molecular / Q000379:methods; D006801:Humans; D008148:Lovastatin / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics
D000924:Anticholesteremic Agents; D008148:Lovastatin