Flavin-Dependent Monooxygenase Kmy13 Mediates Formation of the Carbocyclic <i>ansa</i> System during Kendomycin B Biosynthesis
Kendomycin B is distinguished from other ansamycins by its unique, fully carbogenic <i>ansa</i> scaffold. We show here that FAD-dependent monooxygenase Kmy13 is solely responsible for installing the rare <i>ansa</i> structural framework; <i>in vivo</i> gene disruption/complementation experiments and <i>in vitro</i> enzymatic assays are described in detail. Moreover, the compound with a β-keto ester, kendolactone A (<b>2</b>), was confirmed as the natural substrate of Kmy13 and a bona fide biosynthetic intermediate en route to kendomycin B. Further structural prediction and biochemical assays have provided significant insights into the catalytic mechanism of Kmy13.
Authors
- Yu‐Cheng Gu (ORCID: https://orcid.org/0000-0002-6400-6167)
- Jianhua Ju (ORCID: https://orcid.org/0000-0001-7712-8027)
- Shanwen Zhang (ORCID: https://orcid.org/0000-0002-4534-5358)
- Hongjie Zhu (ORCID: https://orcid.org/0000-0002-2604-033X)
- Ming Peng (ORCID: https://orcid.org/0009-0009-9710-639X)
- Qinglian Li (ORCID: https://orcid.org/0000-0002-4052-9801)
- Jiang Chen (ORCID: https://orcid.org/0000-0001-9215-0396)
Institutions
- Shandong University (CN)
- Chinese Academy of Sciences (CN)
- Syngenta (United Kingdom) (GB)
- Institute of Oceanology (CN)
- South China Sea Institute Of Oceanology (CN)
- University of Chinese Academy of Sciences (CN)
- Syngenta (Switzerland) (CH)
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2024-10-06
- DOI
- https://doi.org/10.1021/jacs.4c08774
- Citations
- 2
- Primary Topic
- Microbial Natural Products and Biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 0.90
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Guangdong Province
- Syngenta International
- Shenzhen Bay Laboratory
- Guangdong Province Introduction of Innovative R&D Team
- National Key Research and Development Program of China
- Major Science and Technology Project of Hainan Province