Cyclization mechanism for the synthesis of macrocyclic antibiotic lankacidin in Streptomyces rochei

被引：86

作者：

Arakawa, K ^{[1
]}

Sugino, F ^{[1
]}

Kodama, K ^{[1
]}

Ishii, T ^{[1
]}

Kinashi, H ^{[1
]}

机构：

[1] Hiroshima Univ, Grad Sch Adv Sci Matter, Dept Mol Biotechnol, Higashihiroshima 7398530, Japan

来源：

CHEMISTRY & BIOLOGY | 2005年 / 12卷 / 02期

关键词：

D O I：

10.1016/j.chembiol.2005.01.009

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：249 / 256

页数：8

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