Characterization of the azinomycin B biosynthetic gene cluster revealing a different iterative type I polyketide synthase for naphthoate biosynthesis

被引：96

作者：

Zhao, Qunfei ^{[1
]}

He, Qingli ^{[1
]}

Ding, Wei ^{[1
,2
]}

Tang, Mancheng ^{[1
]}

Kang, Qianjin ^{[1
,3
]}

Yu, Yi ^{[1
,3
]}

Deng, Wei ^{[1
]}

Zhang, Qi ^{[1
]}

Fang, Jie ^{[1
]}

Tang, Gongli ^{[1
]}

Liu, Wen ^{[1
,3
]}

机构：

[1] Chinese Acad Sci, State Key Lab Bioorgan & Nat Prod Chem, Shanghai Inst Organ Chem, Shanghai 200032, Peoples R China

[2] Lanzhou Univ, Sch Life Sci, Lanzhou 730000, Peoples R China

[3] Shanghai Jiao Tong Univ, Lab Microbial Metab, Sch Life Sci & Biotechnol, Shanghai 200030, Peoples R China

来源：

CHEMISTRY & BIOLOGY | 2008年 / 15卷 / 07期

基金：

中国国家自然科学基金;

关键词：

D O I：

10.1016/j.chembiol.2008.05.021

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：

Azinomycin B is a complex natural product containing densely assembled functionalities with potent antitumor activity. Cloning and sequence analysis of the azi gene cluster revealed an iterative type I polyketide synthase (PKS) gene, five nonribosomal peptide synthetases (NRPSs) genes and numerous genes encoding the biosynthesis of unusual building blocks and tailoring steps for azinomycin B production. Characterization of AziB as a 5-methyl-naphthoic acid (NP) synthase showed a distinct selective reduction pattern in aromatic polyketide biosynthesis governed by bacterial iterative type I PKSs. Heterologous expression established the PKS-post modification route from 5-methyl-NPA to reach the first building block 3-methoxy-5-methyl-NPA. This proposed azinomycin B biosynthetic pathway sets the stage to investigate the enzymatic mechanisms for building structurally unique and pharmaceutically important groups, including the unprecedented azabicyclic ring system and highly active epoxide moiety.

引用

页码：693 / 705

页数：13

共 32 条

[31] Comparative Characterization of the Lactimidomycin and iso-Migrastatin Biosynthetic Machineries Revealing Unusual Features for Acyltransferase-less Type I Polyketide Synthases and Providing an Opportunity To Engineer New Analogues
Seo, Jeong-Woo
Ma, Ming
Kwong, Thomas
Ju, Jianhua
Lim, Si-Kyu
Jiang, Hui
Lohman, Jeremy R.
Yang, Chunying
Cleveland, John
Zazopoulos, Emmanuel
Farnet, Chris M.
Shen, Ben
BIOCHEMISTRY, 2014, 53 (49) : 7854 - 7865
[32] Five novel mutations in CYP11B2 gene detected in patients with aldosterone synthase deficiency type I: Functional characterization and structural analyses
Nguyen, Huy-Hoang
Hannemann, Frank
Hartmann, Michaela F.
Malunowicz, Ewa M.
Wudy, Stefan A.
Bernhardt, Rita
MOLECULAR GENETICS AND METABOLISM, 2010, 100 (04) : 357 - 364

← 1 2 3 4 →