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Updated: Jun 4, 2025

Biosynthesis of a Flavonol from a Flavanone by Establishing a One-pot Bienzymatic Cascade
Published on: August 14, 2019
Multienzyme Cascade Catalyzed Skeleton Rearrangement in a Caged Polyketide Biosynthesis
Jia-Liang Zhou1, Qiu-Yue Nie1, Xian-Feng Hou1
1State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences (CAS), CAS, Shanghai 200032, China.
Abstract:
Rearrangement of the skeleton is crucial for improving the structural complexity and diversity of type II polyketide natural products. In this study, we investigated the rearrangement process from a planar aromatic tetracyclic intermediate to the caged lactones, which is managed by five oxidoreductases. We chemically synthesized the proposed linear tetracyclic substrate, validated the transformation process through in vivo and in vitro experiments, and elucidated the enzyme-catalyzed mechanism using isotope labeling. Significantly, a short-chain dehydrogenase TjhD5 was discovered to play a multifunctional role for multistep reactions.
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