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Published on: January 19, 2016
Trifluoromethylation of Antimycin via Extender Unit Incorporation Improves Antifungal Potency
Jun Zhang1,2,3, Qian Yun1,3, Yuhan Dai2,3
1School of Pharmacy, Fudan University, 826 Zhangheng Rd., Shanghai 201203, China.
Abstract:
We report the first biosynthesis of trifluoromethyl (TFM)-containing extender unit and its incorporation into the polyketide biosynthetic pathway. Using engineered enzymes UkaQFAV 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 7S-epimer. The TFM-modified antimycin derivatives exhibited significantly enhanced antifungal activity, providing a new strategy for polyketide diversification and drug development.
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