Gene Cluster Directs Diversified Carbazole Biosynthesis via Cooperative Halogenation, Hydroxylation, and Methylation
Chlocarbazomycins are bioactive carbazoles with therapeutic potential. Here, we report a conserved gene cluster (<i>ccz</i>) that directs its biosynthesis via a novel pathway. This cluster encodes a versatile tailoring system, including a regioselective halogenase (CczH), dedicated hydroxylases (CczA/J/D), and a bifunctional methyltransferase (CczI) that iteratively methylates and accelerates N-OH dehydroxylation. Our findings provide new enzymes for carbazole pathway engineering and structural diversification.
Authors
- Zijun Xiao (ORCID: https://orcid.org/0009-0002-2696-5727)
- Qiaoling Wu
- Jianhua Ju (ORCID: https://orcid.org/0000-0001-7712-8027)
- Xinpeng Tian (ORCID: https://orcid.org/0000-0001-5871-0062)
- Xiang Weng
- Ming Peng (ORCID: https://orcid.org/0000-0003-2819-046X)
- Hongjie Zhu (ORCID: https://orcid.org/0000-0002-2604-033X)
- Yingying Chen (ORCID: https://orcid.org/0000-0003-0817-7612)
- Feng Li (ORCID: https://orcid.org/0000-0001-5868-7456)
Institutions
- Shandong University (CN)
- Chinese Academy of Sciences (CN)
- South China Sea Institute Of Oceanology (CN)
- Ministry of Education (TH)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-12-05
- DOI
- https://doi.org/10.1021/acs.orglett.5c04621
- Primary Topic
- Microbial Natural Products and Biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 0.00