Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 60, Issue 12, Pages 6639-6645Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202015442
Keywords
antibiotics; biosynthesis; fungus; macrolides; self-resistance
Categories
Funding
- National Key Research and Development Program of China [2018YFA0901900]
- CAMS Innovation Fund for Medical Sciences [CIFMS 2017-I2M-4-004, 2019-I2M-1-005]
- China Postdoctoral Science Foundation [2018M630113]
Ask authors/readers for more resources
A unique self-resistance mechanism for fungal antibiotics was discovered, utilizing an oxidative-reductive cycle to prevent self-harm. This work contributes to the understanding of antibiotic biosynthesis and resistance mechanisms.
Self-resistance genes are employed by many microbial producers of bioactive natural products to avoid self-harm. Herein, we describe a unique strategy for self-resistance toward a macrolide antibiotic, A26771B (1), identified by elucidating its biosynthetic pathway in the fungus Penicillium egyptiacum. A highly reducing polyketide synthase and a trans-acting thioesterase generate the macrolide backbone, and a cytochrome P450 and an acyltransferase, respectively catalyze hydroxylation and succinylation to form the prodrug berkeleylactone E (2). Then, extracellular oxidative activation by a secreted flavin-dependent oxidase forms 1, while intracellular reductive inactivation by a short-chain reductase reforms 2, forming a redox cycle. Our work illustrates a unique redox-mediated resistance mechanism for fungal antibiotics and contributes to the understanding of antibiotic biosynthesis and resistance.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available