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Updated: May 29, 2025

Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine
Published on: June 13, 2022
A Stereoselective Decarboxylative Aromatase/Cyclase Directs the Biosynthesis of an Axially Chiral Biphenyl Framework
Kai Jiang1,2, Cheng Zhu1, Xiaoli Yan1,2
1State Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
Abstract:
Aromatic polyketides are an important class of natural products with various bioactivities, and their structural diversity arises from modifications to their aromatic frameworks. In this study, we identify a stereoselective aromatase/cyclase (ARO/CYC) FasU, which is responsible for forming the axial chiral biphenyl framework in fasamycin. FasU catalyzes sequential decarboxylation and cyclization/aromatization with strict S-stereospecificity on a previously unidentified biosynthetic intermediate. Through crystal structure analysis and site-directed mutagenesis, we reveal the enzyme's substrate binding mode, stereospecificity, and the key residues involved in catalysis. This discovery introduces a novel class of ARO/CYC enzymes in type II polyketide biosynthesis, advancing the development of biocatalysts for chiral aromatic polyketides.
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