Bao W, Sheldon P J, Wendt-Pienkowski E, Hutchinson C R
School of Pharmacy, University of Wisconsin, Madison, Wisconsin 53706, USA.
J Bacteriol. 1999 Aug;181(15):4690-5. doi: 10.1128/JB.181.15.4690-4695.1999.
The starter unit used in the biosynthesis of daunorubicin is propionyl coenzyme A (CoA) rather than acetyl-CoA, which is used in the production of most of the bacterial aromatic polyketides studied to date. In the daunorubicin biosynthesis gene cluster of Streptomyces peucetius, directly downstream of the genes encoding the beta-ketoacyl:acyl carrier protein synthase subunits, are two genes, dpsC and dpsD, encoding proteins that are believed to function as the starter unit-specifying enzymes. Recombinant strains containing plasmids carrying dpsC and dpsD, in addition to other daunorubicin polyketide synthase (PKS) genes, incorporate the correct starter unit into polyketides made by these genes, suggesting that, contrary to earlier reports, the enzymes encoded by dpsC and dpsD play a crucial role in starter unit specification. Additionally, the results of a cell-free synthesis of 21-carbon polyketides from propionyl-CoA and malonyl-CoA that used the protein extracts of recombinant strains carrying other daunorubicin PKS genes to which purified DpsC was added suggest that this enzyme has the primary role in starter unit discrimination for daunorubicin biosynthesis.
柔红霉素生物合成中使用的起始单元是丙酰辅酶A（CoA），而不是乙酰辅酶A，乙酰辅酶A用于迄今为止研究的大多数细菌芳香族聚酮化合物的生产。在产红色链霉菌的柔红霉素生物合成基因簇中，在编码β-酮酰基：酰基载体蛋白合成酶亚基的基因的直接下游，有两个基因dpsC和dpsD，它们编码的蛋白质被认为是作为起始单元特异性酶发挥作用。除了其他柔红霉素聚酮合酶（PKS）基因外，含有携带dpsC和dpsD质粒的重组菌株将正确的起始单元整合到由这些基因合成的聚酮化合物中，这表明，与早期报道相反，dpsC和dpsD编码的酶在起始单元特异性方面起着关键作用。此外，使用携带其他柔红霉素PKS基因的重组菌株的蛋白质提取物，从丙酰辅酶A和丙二酰辅酶A进行21碳聚酮化合物的无细胞合成结果表明，添加了纯化的DpsC后，这种酶在柔红霉素生物合成的起始单元识别中起主要作用。
