Bao W, Sheldon P J, Hutchinson C R
School of Pharmacy and Department of Bacteriology, University of Wisconsin, Madison 53706, USA.
Biochemistry. 1999 Jul 27;38(30):9752-7. doi: 10.1021/bi990751h.
Biosynthesis of the polyketide-derived carbon skeleton of daunorubicin (DNR) begins with propionate rather than acetate, which is the starter unit for most other aromatic polyketides. The dpsCgene has been implicated in specifying the unique propionate-starter unit, and it encodes a protein that is very similar to the Escherichia coli beta-ketoacyl:acyl carrier protein (ACP) synthase III (FabH or KS III) enzyme of fatty acid biosynthesis. Purified DpsC was found to use propionyl-coenzyme A as substrate and to be acylated by propionate at the Ser-118 residue. DpsC exhibits KS III activity in catalyzing the condensation of propionyl-CoA and malonyl-ACP, and also functions as an acyltransferase in the transfer of propionate to an ACP. The DpsC enzyme has a high-substrate specificity, utilizing only propionyl-CoA, and not malonyl-CoA, 2-methylmalonyl-CoA or acetyl-CoA, as the starter unit of DNR biosynthesis.
柔红霉素（DNR）的聚酮衍生碳骨架的生物合成起始于丙酸盐而非乙酸盐，乙酸盐是大多数其他芳香族聚酮的起始单元。dpsC基因与确定独特的丙酸盐起始单元有关，它编码一种与脂肪酸生物合成中大肠杆菌β-酮酰基：酰基载体蛋白（ACP）合酶III（FabH或KS III）酶非常相似的蛋白质。发现纯化的DpsC以丙酰辅酶A作为底物，并在Ser-118残基处被丙酸盐酰化。DpsC在催化丙酰辅酶A和丙二酰ACP缩合时表现出KS III活性，并且在将丙酸盐转移到ACP时还充当酰基转移酶。DpsC酶具有高底物特异性，仅利用丙酰辅酶A作为DNR生物合成的起始单元，而不利用丙二酰辅酶A、2-甲基丙二酰辅酶A或乙酰辅酶A。
