Biosynthesis of Antituberculosis Antibiotic Capreomycin Involves a <i>trans</i>-Iterative Adenylation Domain within the Nonribosomal Peptide Synthetase Machinery
Capreomycin (CMN) is a nonribosomal peptide (NRP) antituberculosis antibiotic. CMN biosynthesis involves a non-canonical <i>trans</i>-iterative adenylation (A) domain. Here, we report that the A domain-less nonribosomal peptide synthetase (NRPS) module CmnI utilizes another module's A domain CmnA-A<sub>1</sub> to load the required amino acid onto its thiolation (T) domain. This study provides evidence of an unusual mode of NRP biosynthesis in bacteria, involving a <i>trans</i>-iterative A domain in the NRPS machinery.
Authors
- John Chu (ORCID: https://orcid.org/0000-0002-7033-7229)
- Yi‐Ting Lai (ORCID: https://orcid.org/0000-0002-5662-2090)
- Chin‐Yuan Chang (ORCID: https://orcid.org/0000-0001-7314-3967)
- You-Min Kuo
- Thomas Ma (ORCID: https://orcid.org/0000-0001-8466-0388)
- Yarong Chen (ORCID: https://orcid.org/0000-0002-2600-6756)
- Sheng‐Cih Huang
- Yung‐Lin Wang (ORCID: https://orcid.org/0000-0003-3342-4160)
- Chia Hsieh (ORCID: https://orcid.org/0000-0002-3715-4113)
- Changlian Peng
- Yean‐Kuo Luo
- Yen-Cheng Lin (ORCID: https://orcid.org/0000-0002-8748-6108)
- Po‐Yun Hsiao
- Hsiao-Tzu Liao
Institutions
- National Yang Ming Chiao Tung University (TW)
- Kaohsiung Medical University (TW)
- National Taiwan University (TW)
- Genomics Research Center, Academia Sinica (TW)
- Intelligent Systems Research (United States) (US)
- RIKEN Center for Emergent Matter Science (JP)
- Genomics (United Kingdom) (GB)
- International Drug Development (FR)
- Academia Sinica (TW)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-08-15
- DOI
- https://doi.org/10.1021/acs.orglett.5c03112
- Citations
- 1
- Primary Topic
- Microbial Natural Products and Biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 1.39
Funders
- Kaohsiung Medical University
- National Science and Technology Council