Polyunsaturated fatty-acid-like trans-enoyl reductases utilized in polyketide biosynthesis.
Polyketide biosynthesis is typically directed by cis-acting catalytic domains. In the case of the Bacillus subtilis secondary metabolite dihydrobacillaene, the cis-acting domains are not sufficient to generate the saturated C14'-C15' bond. In this communication, we identify PksE as a trans-acting enoyl reductase utilized in the biosynthesis of this portion of dihydrobacillaene. PksE is homologous to the enzymes predicted to serve as enoyl reductases in polyunsaturated fatty acid (PUFA) biosynthesis, and we confirmed this functional assignment in vitro. These results suggest a general enoyl reduction pathway in polyketide biosynthesis and a means by which PUFA-like biosynthetic machinery can modulate small-molecule function.
Bumpus
Stefanie B
SB
Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, Illinois 61801, USA.
Magarvey
Nathan A
NA
Kelleher
Neil L
NL
Walsh
Christopher T
CT
Calderone
Christopher T
CT
D001412:Bacillus subtilis / Q000201:enzymology; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000378:metabolism*; D018942:Macrolides / Q000737:chemistry / Q000378:metabolism*; D010088:Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D048630:Polyketide Synthases / Q000737:chemistry / Q000378:metabolism
D005231:Fatty Acids, Unsaturated; D018942:Macrolides; D048630:Polyketide Synthases; D010088:Oxidoreductases