Cyclization mechanism for the synthesis of macrocyclic antibiotic lankacidin in Streptomyces rochei
Cyclization mechanism for the synthesis of macrocyclic antibiotic lankacidin in Streptomyces rochei
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DOI：
10.1016/j.chembiol.2005.01.009
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发表时间：
2005-02-01
影响因子：
--
通讯作者：
Kinashi, H
中科院分区：
文献类型：
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作者：
Arakawa, K;Sugino, F;Kinashi, H
链霉菌7434 AN 4中兰卡菌素生物合成基因簇跨越巨大线性质粒pSLA 2-L的31 kb，包含聚酮合酶（PKS）/非核糖体肽合成酶（NRPS）杂合基因（IkcA）、I型PKS基因和吡咯喹啉醌（PQQ）生物合成基因（IkcK-IkcO）。饲养PQQ的pqq突变恢复兰卡菌素生产，这表明其在氧化过程中的关键作用。然而，17元大环的形成不是由PQQ依赖性脱氢酶（Orf 23）催化的，而是由黄素依赖性胺氧化酶（LkcE）催化的。从IkcE破坏物分离的化合物LC-KA 05是缺乏C2-C18键的无环中间体。这些结果提示了lankacidin大环骨架合成的环化机理。
The lankacidin biosynthetic gene cluster in Streptomyces rochei strain 7434AN4 was found to span 31 kb of the giant linear plasmid pSLA2-L and contain a polyketide synthase (PKS)/nonribosomal peptide synthetase (NRPS) hybrid gene (IkcA), type I PKS genes, and pyrroloquinoline quinone (PQQ) biosynthetic genes (IkcK-IkcO). Feeding of PQQ to a pqq mutant restored the lankacidin production, suggesting its crucial role in an oxidation process. However, formation of the 17-membered macrocyclic ring was not catalyzed by PQQ-dependent dehydrogenase (Orf23), but was by flavin-dependent amine oxidase (LkcE). Compound LC-KA05 isolated from an IkcE disruptant was an acyclic intermediate lacking the C2-C18 linkage. These results suggested a cyclization mechanism for the synthesis of the lankacidin macrocyclic skeleton.