上海交通大学瞿旭东团队报道了立体选择性脱羧芳香化酶/环化酶法沙霉引导素轴手性联苯框架的生物合成。相关研究成果发表在2025年2月6日出版的《美国化学会杂志》。

芳香族聚酮是一类重要的天然产物，具有多种生物活性，其结构多样性源于芳香族框架的修饰。

该文中，研究人员鉴定了一种立体选择性芳香化酶/环化酶（ARO/CYC）FasU，它负责在法沙霉素中形成轴向手性联苯框架。FasU在以前未鉴定的生物合成中间体上以严格的S-立体特异性催化顺序脱羧和环化/芳构化。通过晶体结构分析和定点突变，研究人员揭示了酶的底物结合模式、立体特异性和参与催化的关键残基。

该发现在II型聚酮生物合成中引入了一类新的ARO/CYC酶，推动了手性芳香族聚酮生物催化剂的发展。

附：英文原文

Title: A Stereoselective Decarboxylative Aromatase/Cyclase Directs the Biosynthesis of an Axially Chiral Biphenyl Framework in Fasamycin

Author: Kai Jiang, Cheng Zhu, Xiaoli Yan, Guangjun Li, Zhi Lin, Zixin Deng, Shukun Luo, Xudong Qu

Issue&Volume: February 6, 2025

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.

DOI: 10.1021/jacs.4c18376

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c18376