title: Broad substrate specificity of the loading didomain of the lipomycin polyketide synthase.
abstract: LipPks1, a polyketide synthase subunit of the lipomycin synthase, is believed to catalyze the polyketide chain initiation reaction using isobutyryl-CoA as a substrate, followed by an elongation reaction with methylmalonyl-CoA to start the biosynthesis of antibiotic α-lipomycin in Streptomyces aureofaciens Tü117. Recombinant LipPks1, containing the thioesterase domain from the 6-deoxyerythronolide B synthase, was produced in Escherichia coli, and its substrate specificity was investigated in vitro. Surprisingly, several different acyl-CoAs, including isobutyryl-CoA, were accepted as the starter substrates, while no product was observed with acetyl-CoA. These results demonstrate the broad substrate specificity of LipPks1 and may be applied to producing new antibiotics.
authors.affiliation: QB3 Institute, University of California, Berkeley, California 94270, United States.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yuzawa
authors.forename: Clara H
authors.initials: CH
authors.lastname: Eng
authors.forename: Leonard
authors.initials: L
authors.lastname: Katz
authors.forename: Jay D
authors.initials: JD
authors.lastname: Keasling
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology; D006027:Glycosides / Q000096:biosynthesis; D011090:Polyenes; D048630:Polyketide Synthases / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013304:Streptomyces aureofaciens / Q000201:enzymology; D013379:Substrate Specificity
chemical_list: D000214:Acyl Coenzyme A; D006027:Glycosides; D011090:Polyenes; C548829:alpha-lipomycin; C015357:methylmalonyl-coenzyme A; D048630:Polyketide Synthases