Insights into the Biosynthesis of Hormaomycin, An Exceptionally Complex Bacterial Signaling Metabolite

被引：89

作者：

Hoefer, Ivonne ^{[2
]}

Cruesemann, Max ^{[1
]}

Radzom, Markus ^{[3
]}

Geers, Bernadette ^{[3
]}

Flachshaar, Daniel ^{[1
]}

Cai, Xiaofeng ^{[1
]}

Zeeck, Axel ^{[3
]}

Piel, Joern ^{[1
]}

机构：

[1] Univ Bonn, Kekule Inst Organ Chem & Biochem, D-53121 Bonn, Germany

[2] Max Planck Inst Chem Ecol, Dept Bioorgan Chem, D-07745 Jena, Germany

[3] Univ Gottingen, Inst Organ & Biomol Chem, D-37077 Gottingen, Germany

来源：

CHEMISTRY & BIOLOGY | 2011年 / 18卷 / 03期

关键词：

MBTH-LIKE PROTEIN; NONRIBOSOMAL PEPTIDE SYNTHETASES; PRECURSOR-DIRECTED BIOSYNTHESIS; GENE-CLUSTER; SECONDARY METABOLISM; STREPTOMYCES-COELICOLOR; ANTIBIOTIC PRODUCTION; ADENYLATION DOMAINS; LINCOMYCIN; CLOROBIOCIN;

D O I：

10.1016/j.chembiol.2010.12.018

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：

Hormaomycin produced by Streptomyces griseoflavus is a structurally highly modified depsipeptide that contains several unique. building blocks with cyclopropyl, nitro, and chlorine moieties. Within the genus Streptomyces, it acts as a bacterial hormone that induces morphological differentiation and the production of bioactive secondary metabolites. In addition, hormaomycin is an extremely potent narrow-spectrum antibiotic. In this study, we shed light on hormaomycin biosynthesis by a combination of feeding studies, isolation of the biosynthetic nonribosomal peptide synthetase (NRPS) gene cluster, and in vivo and in vitro functional analysis of enzymes. In addition, several nonnatural hormaomycin congeners were generated by feeding-induced metabolic rerouting. The NRPS contains numerous highly repetitive regions that suggest an evolutionary scenario for this unusual bacterial hormone, providing new opportunities for evolution-inspired metabolic engineering of novel nonribosomal peptides.

引用

页码：381 / 391

页数：11

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