Inactivation of P450 Reprograms the Ring Topology of Glycopeptide Antibiotics
Glycopeptide antibiotics (GPAs) are the drugs of choice for life-threatening Gram-positive infections and feature a biphenolic coupling cross-linked peptide scaffold constructed by certain P450s in a strict sequence- and position-specific manner. However, in situ point mutation of P450 within the fumamycin biosynthetic gene cluster uncovered new derivatives possessing previously inaccessible cross-link patterns, suggesting that P450 inactivation can reprogram the ring topology of GPAs and thereby could be used to expand their chemical space.
Authors
- Mingzhu Mao
- Mengru Wang (ORCID: https://orcid.org/0000-0002-2543-4871)
- Xu M (ORCID: https://orcid.org/0009-0006-2255-3273)
- Xingkun Li
- Zixin Deng
- Sa Zhou
- Weiqian Qi
Institutions
- Tianjin University of Science and Technology (CN)
- Chinese Academy of Sciences (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
- 2026-06-09
- DOI
- https://doi.org/10.1021/acs.orglett.6c01960
- Primary Topic
- Microbial Natural Products and Biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Tianjin City
- National Key Research and Development Program of China