Arakawa Kenji, Sugino Fuminori, Kodama Kazuya, Ishii Tatsuya, Kinashi Haruyasu
Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8530, Japan.
Chem Biol. 2005 Feb;12(2):249-56. doi: 10.1016/j.chembiol.2005.01.009.
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 (lkcA), type I PKS genes, and pyrroloquinoline quinone (PQQ) biosynthetic genes (lkcK-lkcO). 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 lkcE disruptant was an acyclic intermediate lacking the C2-C18 linkage. These results suggested a cyclization mechanism for the synthesis of the lankacidin macrocyclic skeleton.
人们发现罗氏链霉菌7434AN4菌株中的兰卡杀菌素生物合成基因簇跨越巨大的线性质粒pSLA2-L上的31 kb，包含一个聚酮合酶（PKS）/非核糖体肽合成酶（NRPS）杂交基因（lkcA）、I型PKS基因以及吡咯喹啉醌（PQQ）生物合成基因（lkcK-lkcO）。向pqq突变体投喂PQQ可恢复兰卡杀菌素的产生，表明其在氧化过程中起关键作用。然而，17元大环的形成并非由PQQ依赖的脱氢酶（Orf23）催化，而是由黄素依赖的胺氧化酶（LkcE）催化。从lkcE缺失突变体中分离出的化合物LC-KA05是一种缺乏C2-C18连接的无环中间体。这些结果提示了兰卡杀菌素大环骨架合成的环化机制。
