编码结构相关多烯复合物的完整FR-008/杀假丝菌素基因簇的组织和突变分析

Organizational and mutational analysis of a complete FR-008/candicidin gene cluster encoding a structurally related polyene complex.

作者信息

Chen Shi, Huang Xi, Zhou Xiufen, Bai Linquan, He Jing, Jeong Ki Jun, Lee Sang Yup, Deng Zixin

机构信息

Bio-X Life Science Research Center and School of Life Science and Biotechnology, Shanghai Jiaotong University, 200030, Shanghai, China.

出版信息

Chem Biol. 2003 Nov;10(11):1065-76. doi: 10.1016/j.chembiol.2003.10.007.

DOI:10.1016/j.chembiol.2003.10.007

PMID:14652074

Abstract

The complete gene cluster for biosynthesis of a polyene complex, FR-008, spans 137.2 kb of the genome of Streptomyces sp. FR-008 consisting of six genes for a modular PKS and 15 additional genes. The extensive similarity to the partially characterized candicidin gene cluster in Streptomyces griseus IMRU3570, especially for genes involved in mycosamine biosynthesis, prompted us to compare the compounds produced by Streptomyces sp. FR-008 and Streptomyces griseus IMRU3570, and we found that FR-008 and candicidin complex are identical. A model for biosynthesis of a set of four structurally related FR-008/candicidin compounds was proposed. Deletion of the putative regulatory genes abolished antibiotic production, while disruption of putative glycosyltransferase and GDP-ketosugar aminotransferase functionalities led to the productions of a set of nonmycosaminated aglycones and a novel polyene complex with attachment of altered sugar moiety, respectively.

摘要

用于合成多烯复合物FR - 008的完整基因簇跨越链霉菌属FR - 008基因组的137.2 kb，由一个模块化聚酮合酶的六个基因和另外15个基因组成。与灰色链霉菌IMRU3570中部分特征明确的杀假丝菌素基因簇具有广泛相似性，特别是对于参与肌醇胺生物合成的基因，这促使我们比较链霉菌属FR - 008和灰色链霉菌IMRU3570产生的化合物，我们发现FR - 008和杀假丝菌素复合物是相同的。提出了一组四种结构相关的FR - 008/杀假丝菌素化合物的生物合成模型。推定调控基因的缺失消除了抗生素的产生，而推定糖基转移酶和GDP - 酮糖氨基转移酶功能的破坏分别导致了一组非肌醇胺化苷元的产生和一种带有改变糖部分连接的新型多烯复合物的产生。