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Convergent biosynthetic transformations to a bacterial specialized metabolite
Yi-Ling Du1, Melanie A Higgins2, Guiyun Zhao3
1Institute of Pharmaceutical Biotechnology and The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. yldu@zju.edu.cn.
Nature Chemical Biology
|August 14, 2019
Summary
Marine microbes create the antibiotic indolmycin using a unique pathway distinct from terrestrial bacteria. This discovery reveals novel biosynthetic enzymes and improves antibiotic production.
Area of Science:
- Microbial secondary metabolism
- Natural product biosynthesis
- Enzyme mechanisms
Background:
- Microbes produce specialized metabolites for survival.
- Distinct biosynthetic pathways for the same metabolite are rare.
- Indolmycin is an antibiotic produced by both marine and terrestrial microbes.
Discussion:
- The marine Pseudoalteromonas luteoviolacea pathway uses a shunt product as a substrate for a novel metal-independent N-demethylindolmycin synthase.
- The terrestrial Streptomyces pathway employs a different mechanism.
- Structural analysis elucidated the enzyme's active site and reaction mechanism.
Key Insights:
- A novel metal-independent N-demethylindolmycin synthase was identified in P. luteoviolacea.
- The structure of the enzyme in complex with its product was determined at 1.5 Å resolution.
- Biosynthetic insights enabled engineering of the Streptomyces pathway for improved indolmycin production.
Outlook:
- This study offers a new model for understanding the evolution of distinct biosynthetic routes.
- Further research can explore other specialized metabolites with potentially divergent pathways.
- The findings could lead to the development of new antimicrobial agents.
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