Biosynthesis of salinosporamides from alpha,beta-unsaturated fatty acids: implications for extending polyketide synthase diversity.
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.
Liu
Yuan
Y
Scripps Institution of Oceanography, University of California at San Diego, La Jolla, California 92093-0204, USA.
Hazzard
Christopher
C
Eustáquio
Alessandra S
AS
Reynolds
Kevin A
KA
Moore
Bradley S
BS
D000192:Actinomycetales / Q000378:metabolism; D000214:Acyl Coenzyme A / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D007769:Lactams / Q000737:chemistry / Q000378:metabolism*; D048630:Polyketide Synthases / Q000378:metabolism*
D000214:Acyl Coenzyme A; D005231:Fatty Acids, Unsaturated; D007769:Lactams; C015357:methylmalonyl-coenzyme A; D048630:Polyketide Synthases