Trifluoromethylation of Antimycin via Extender Unit Incorporation Improves Antifungal Potency
We report the first biosynthesis of trifluoromethyl (TFM)-containing extender unit and its incorporation into the polyketide biosynthetic pathway. Using engineered enzymes UkaQ<sup>FAV</sup> and Arm13-ACCase, we synthesized a TFM-containing extender unit, which was successfully integrated into the antimycin structure. This modification resulted in stereochemical changes, leading to the formation of an unusual 7<i>S</i>-epimer. The TFM-modified antimycin derivatives exhibited significantly enhanced antifungal activity, providing a new strategy for polyketide diversification and drug development.
Authors
- Xudong Qu (ORCID: https://orcid.org/0000-0002-3301-8536)
- Yun Qian (ORCID: https://orcid.org/0000-0003-1600-5693)
- Jun Zhang (ORCID: https://orcid.org/0000-0002-4379-3616)
- Zixin Deng (ORCID: https://orcid.org/0000-0003-0724-3390)
- Yuhan Dai (ORCID: https://orcid.org/0009-0005-5233-156X)
- Mengmeng Zheng (ORCID: https://orcid.org/0000-0003-0276-0516)
- Chun Lei
- Zhi Xiu Lin (ORCID: https://orcid.org/0009-0005-2240-449X)
Institutions
- Shanghai Jiao Tong University (CN)
- Fudan University (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-04-21
- DOI
- https://doi.org/10.1021/acs.orglett.5c01134
- Citations
- 1
- Primary Topic
- Fluorine in Organic Chemistry
- Type
- article
- Field-Weighted Citation Impact
- 0.79
Funders
- Natural Science Foundation of Shanghai
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Science and Technology Commission of Shanghai Municipality
- Program of Shanghai Academic Research Leader