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Biosynthesis of Salinosporamides from α,β-Unsaturated Fatty Acids: Implications for Extending Polyketide Synthase Diversity

2009; American Chemical Society; Volume: 131; Issue: 30 Linguagem: Inglês

10.1021/ja9042824

1943-2984

Yuan Liu, Christopher Hazzard, Alessandra S. Eustáquio, Kevin A. Reynolds, Bradley S. Moore,

Enzyme Structure and Function

A new series of coenzyme A-tethered polyketide synthase extender units were discovered in relation to the biosynthesis of the salinosporamide family of anticancer agents from the marine bacterium Salinispora tropica. In vivo and in vitro experiments revealed that the crotonyl-CoA reductase/carboxylase SalG has broad substrate tolerance toward 2-alkenyl-CoAs that give rise to the salinosporamide C-2 substitution pattern.