Discovery and Biosynthesis of Lipolasso Peptides Reveal CoA-transferase for Tyrosine Lipidation of Ribosomal Peptides
Lipopeptides are bioactive molecules typically produced via nonribosomal pathways. Only four types of lipidated ribosomally synthesized and post-translationally modified peptides (RiPPs) are known, all modified on amine groups by GNAT enzymes. We report an unprecedented biosynthetic gene cluster combining lasso peptide biosynthesis and acyl-CoA metabolism that produces a novel family of lipolasso peptides. A crotonobetainyl-CoA:carnitine CoA-transferase lipidates the Tyr hydroxy group within precursor peptides, revealing a distinct RiPP lipidation strategy. This work expands the paradigm of ribosomal lipopeptide biosynthesis.
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
- Chuan‐Rui Zhang (ORCID: https://orcid.org/0000-0002-0376-0369)
- Jin-Long Lu
- Yuanyuan Li (ORCID: https://orcid.org/0000-0002-5418-4701)
- Hongping Han
- Xinrong Li (ORCID: https://orcid.org/0000-0002-3188-2929)
- Jiao‐Jiao Cui
- Weixu Zhai (ORCID: https://orcid.org/0009-0002-3203-8348)
- Kun Gao (ORCID: https://orcid.org/0000-0002-3856-3672)
Institutions
- Chinese Academy of Sciences (CN)
- Qinghai Normal University (CN)
- Shanghai Institute of Materia Medica (CN)
- Advanced Research Institute (US)
- State Key Laboratory of Chemical Engineering (CN)
- Lanzhou University (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-10-22
- DOI
- https://doi.org/10.1021/acs.orglett.5c03981
- Citations
- 6
- Primary Topic
- RNA and protein synthesis mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 4.84