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A General Method for Detecting Nitrosamide Formation in the In Vitro Metabolism of Nitrosamines by Cytochrome P450s
Published on: September 25, 2017
Characterizing Two Cytochrome P450s in Tiacumicin Biosynthesis Reveals Reaction Timing for Tailoring Modifications
Ziquan Yu1,2, Haibo Zhang1, Chengshan Yuan1,3
1Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica , South China Sea Institute of Oceanology, Innovation Academy for South China Sea Ecology and Environmental Engineering, Chinese Academy of Sciences , 164 West Xingang Road , Guangzhou 510301 , P. R. China.
Abstract:
Functions of the tailoring enzymes for the biosynthesis of tiacumicin B (1) have been previously determined. However, the reaction timing remains elusive. Herein, we report the in vitro biochemical characterization of two P450 enzymes TiaP1 and TiaP2. The investigation of their substrate scope and kinetic parameters clearly demonstrates that the TiaP2-catalyzed C-20 hydroxylation is the first tailoring step and the TiaP1-catalyzed C-18 hydroxylation is the last step in the biosynthesis of 1.
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