P450 Disruption Reveals Unforeseen Biaryl Cross-Link Chemistry in Glycopeptide Antibiotics

Organic Letters 2026

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Authors: Jiawei Cao, Xingkun Li, Liyuan Zhang, Rui Wang, Zixin Deng, Zhilong Zhao, Mengru Wang, Min Xu
DOI: 10.1021/acs.orglett.6c02291
Cited by: 1
References: 19

Abstract

Glycopeptide antibiotics (GPAs) are the drug of choice for treating multidrug-resistant Gram-positive infections. GPAs possess a unique aromatic amino-acid-rich scaffold interconnected by a diverse set of biaryl cross-links, contributing to their rigid 3D structures for specific target binding on the cell wall. Disruption of the P450 genes responsible for biaryl linkage formation from the biosynthetic gene cluster of varsomycin identified a never-before-seen macrocyclic ring system in GPA, which greatly expands the chemical space of GPAs.

Fields of Study & Subjects

Microbial Natural Products and Biosynthesis Carbohydrate Chemistry and Synthesis Pneumonia and Respiratory Infections

Publication details

Journal / source
Organic Letters
Publisher
American Chemical Society (ACS)
Volume
28
Issue
26
Pages
8481–8486
Publication date
19 June 2026
Language
EN