Discovery and Biosynthesis of Dehydroalanine-Containing Lasso Peptide by a Hybrid Biosynthetic System
Lasso peptides and lanthipeptides are two major classes of ribosomally synthesized and post-translationally modified peptides (RiPPs), each defined by distinct post-translational modification (PTM) enzymes. We identify a hybrid biosynthetic gene cluster that integrates PTM enzymes from both pathways to produce a unique lasso peptide featuring a dehydroalanine residue and C-terminal Asp side-chain methylation. Elucidation of its biosynthesis uncovers unprecedented combinatorial RiPP maturation. This study establishes a paradigm for hybrid RiPP biosynthesis and enables discovery and engineering of novel RiPPs.
Authors
- Xinxiang Lei (ORCID: https://orcid.org/0000-0002-5635-5375)
- Shangwen Luo (ORCID: https://orcid.org/0000-0003-2162-2477)
- Shi‐Hui Dong (ORCID: https://orcid.org/0000-0002-1743-2163)
- Jiang Xiong
- Guohua Lou (ORCID: https://orcid.org/0000-0002-2829-3429)
- Jin-Long Lu
- Hongping Han
- Xinrong Li (ORCID: https://orcid.org/0000-0002-3188-2929)
- Yuxia Ma
- Jiao‐Jiao Cui
- Jinming Di (ORCID: https://orcid.org/0000-0003-4420-3152)
- Weixu Zhai (ORCID: https://orcid.org/0009-0002-3203-8348)
- Kun Gao (ORCID: https://orcid.org/0000-0002-3856-3672)
Institutions
- Qinghai Normal University (CN)
- State Key Laboratory of Chemical Engineering (CN)
- Lanzhou University (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-12-05
- DOI
- https://doi.org/10.1021/acs.orglett.5c04385
- Citations
- 1
- Primary Topic
- Microbial Natural Products and Biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 1.39