P450 Disruption Reveals Unforeseen Biaryl Cross-Link Chemistry in Glycopeptide Antibiotics
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.
Authors
- R Wang
- Mengru Wang (ORCID: https://orcid.org/0000-0002-2543-4871)
- Min Xu (ORCID: https://orcid.org/0000-0002-6661-5177)
- Liyuan Zhang (ORCID: https://orcid.org/0000-0002-7469-1743)
- Jiawei Cao
- Xingkun Li
- Zhilong Zhao
- Zixin Deng
Institutions
- Linyi University (CN)
- State Key Laboratory of Synthetic Chemistry (CN)
- Tianjin Institute of Industrial Biotechnology (CN)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2026-06-18
- DOI
- https://doi.org/10.1021/acs.orglett.6c02291
- Primary Topic
- Microbial Natural Products and Biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 0.00