Broad Substrate Specificity of the Loading Didomain of the Lipomycin Polyketide Synthase
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 alpha-lipomycin in Streptomyces aureofaciens Tu117. 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.
- Sponsoring Organization:
- USDOE Advanced Research Projects Agency - Energy (ARPA-E)
- DOE Contract Number:
- DE-AR0000091
- OSTI ID:
- 1211115
- Journal Information:
- Biochemistry, Vol. 52, Issue 22; ISSN 0006-2960
- Country of Publication:
- United States
- Language:
- English
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