QB3 Institute, University of California, Berkeley, California 94270, United States.
Biochemistry. 2013 Jun 4;52(22):3791-3. doi: 10.1021/bi400520t. Epub 2013 May 23.
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.
LipPks1 是脂肽素合酶的聚酮合酶亚基，被认为使用异丁酰辅酶 A 作为底物催化聚酮链起始反应，然后用甲基丙二酰辅酶 A 进行延伸反应，从而开始在金色链霉菌 Tü117 中合成抗生素 α-脂肽素。含有 6-脱氧赤藓醇 B 合酶硫酯酶结构域的重组 LipPks1 在大肠杆菌中生产，并在体外研究了其底物特异性。令人惊讶的是，几种不同的酰基辅酶 A，包括异丁酰辅酶 A，被接受为起始底物，而乙酰辅酶 A 则没有观察到产物。这些结果表明 LipPks1 具有广泛的底物特异性，可能可用于生产新的抗生素。
