Carboxylic Acid Tailoring in Thioquinolobactin Biosynthesis
The biosynthetic mechanism underlying the formation of thiocarboxylic acid moieties in natural products remains largely unknown. Thioquinolobactin (TQB) is a <i>Pseudomonas fluorescens</i> derived siderophore that contains a thiocarboxylic acid moiety within its structure. Although the biosynthetic gene cluster and proposed pathway for TQB formation have been reported, the biosynthetic mechanism related to the thiocarboxylic acid formation are yet to be fully understood. In this study, we address this question by demonstrating that a unique dual-domain protein QbsL, which possesses both CoA ligase and methyltransferase activities, along with the sulfurtransferase QbsK, facilitates the assembly of the thiocarboxylic acid. Based on this mechanism, we develop a chemoenzymatic method to convert carboxylic acid into selenocarboxylic acid, thereby generating selenium-containing analogues of TQB. These findings resolve the long-standing mystery in TQB biosynthesis and expand the synthetic toolkit for carboxylic acid modification.
Authors
- Yuanning Li (ORCID: https://orcid.org/0000-0002-2206-5804)
- Shanmin Zheng (ORCID: https://orcid.org/0000-0002-7073-3336)
- Ying Lv (ORCID: https://orcid.org/0000-0003-1649-5258)
- Mingyu Liu
- Shengying Li (ORCID: https://orcid.org/0000-0002-5244-870X)
- Jiawei Guo (ORCID: https://orcid.org/0000-0002-8620-6098)
- Xingwang Zhang (ORCID: https://orcid.org/0000-0003-1346-1183)
- Y. L. Feng (ORCID: https://orcid.org/0000-0003-4421-0969)
- Xiaolin Tian (ORCID: https://orcid.org/0009-0008-9529-3227)
- Fangyuan Cheng (ORCID: https://orcid.org/0009-0005-6567-7746)
- Xuan Wang
Institutions
- Shandong University (CN)
- Institute of Marine Biotechnology (DE)
- Qingdao National Laboratory for Marine Science and Technology (CN)
- Istituto di Scienze Marine del Consiglio Nazionale delle Ricerche (IT)
- State Key Laboratory of Microbial Technology
Publication Details
- Journal
- Journal of Natural Products
- Published
- 2025-06-11
- DOI
- https://doi.org/10.1021/acs.jnatprod.5c00331
- Citations
- 1
- Primary Topic
- Enzyme Catalysis and Immobilization
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Shandong Province
- Taishan Scholar Project of Shandong Province
- National Key Research and Development Program of China