Biosynthetic Code for Divergolide Assembly in a Bacterial Mangrove Endophyte

• Published in: Chembiochem : a European journal of chemical biology Vol. 15; no. 9; pp. 1274 - 1279
• Main Authors: Xu, Zhongli, Baunach, Martin, Ding, Ling, Peng, Huiyun, Franke, Jakob, Hertweck, Christian
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 16.06.2014; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: ansamycins; Bacteria; Biochemistry & Molecular Biology; biosynthesis; Bruguiera gymnorrhiza; Chemistry, Medicinal; divergolides; Life Sciences & Biomedicine; Macrolides - chemistry; Macrolides - isolation & purification; Macrolides - metabolism; modular polyketide synthases; Molecular Conformation; Pharmacology & Pharmacy; polyketides; Rhizophoraceae - microbiology; Science & Technology; Streptomyces; Streptomyces - chemistry; Streptomyces - metabolism; ACID; AMYCOLATOPSIS-MEDITERRANEI S699; ansamycins; DOUBLE-BOND MIGRATION; CONFIGURATION; modular polyketide synthases; STEREOCHEMICAL DETERMINATION; MYXOBACTERIUM-SORANGIUM-CELLULOSUM; polyketides; RIFAMYCIN; divergolides; GENE-CLUSTER; biosynthesis; ACTINOSYNNEMA-PRETIOSUM
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.201402071

Divergolides are structurally diverse ansamycins produced by a bacterial endophyte (Streptomyces sp.) of the mangrove tree Bruguiera gymnorrhiza. By genomic analyses a gene locus coding for the divergolide pathway was detected. The div gene cluster encodes genes for the biosynthesis of 3‐amino‐5‐hydroxybenzoate and the rare extender units ethylmalonyl‐CoA and isobutylmalonyl‐CoA, polyketide assembly by a modular type I polyketide synthase (PKS), and enzymes involved in tailoring reactions, such as a Baeyer–Villiger oxygenase. A detailed PKS domain analysis confirmed the stereochemical integrity of the divergolides and provided valuable new insights into the formation of the diverse aromatic chromophores. The bioinformatic analyses and the isolation and full structural elucidation of four new divergolide congeners led to a revised biosynthetic model that illustrates the formation of four different types of ansamycin chromophores from a single polyketide precursor. Digging into divergolide diversity: The molecular basis for the biosynthesis of the divergolides, structurally diverse ansamycins from a mangrove endophyte, was elucidated. Analysis of the assembly line and the full structural elucidation of four new divergolide congeners led to a revised biosynthetic model, which illustrates the formation of four different types of ansamycin chromophores from a single polyketide precursor.