Discovery of Sporachelins by Genome Mining of a <i>Micromonospora</i> Strain
Myxochelins are a group of catecholate siderophores encoded by <i>mxc</i> biosynthetic gene clusters (BGCs). They are mainly produced by myxobacteria and display a wide variety of bioactivities. Herein, we report a group of new myxochelins produced not by a myxobacterial strain but by an actinobacteria strain, <i>Micromonospora</i> sp. TMD166. They consisted of six new compounds, designated as sporachelins A (<b>1</b>), A1 (<b>2</b>), B (<b>3</b>), C (<b>4</b>), D (<b>5</b>), and E (<b>6</b>), and the known compound myxochelin A (<b>7</b>). The planar structures were determined by comprehensive analyses of 1D and 2D NMR spectroscopic data, and the absolute configurations were confirmed by Marfey's analysis and chemical synthesis. The six sporachelins are the first examples of acylated derivatives at the primary alcohol of myxochelin A. These molecules were found to inhibit human 5-lipoxygenase. In addition, <b>1</b>-<b>7</b> exhibited antifibrotic activity in the TGFβ1-induced human hepatic cell line LX-2 by suppressing fibrosis-related genes <i>COL1A1</i>, <i>ACTA2</i>, and <i>TGFB1</i> expression. This is the first report of antifibrotic activity by myxochelins.
Authors
- Maira Saleem
- Zong‐Gen Peng (ORCID: https://orcid.org/0000-0001-7662-6892)
- Fei-Na Li (ORCID: https://orcid.org/0000-0001-6955-2303)
- Cheng‐Hang Sun (ORCID: https://orcid.org/0000-0001-6813-8274)
- Zhong-Ke Jiang
- Yuyu Liu (ORCID: https://orcid.org/0000-0002-3528-2656)
- Adeela Fatima
- Xin Xiang (ORCID: https://orcid.org/0000-0003-3510-5649)
- Hu Li
- Gang Wu (ORCID: https://orcid.org/0000-0002-1798-4849)
- Shaowei Liu (ORCID: https://orcid.org/0000-0002-4614-4857)
- Xiaomeng Hao
- Jixiang Xu (ORCID: https://orcid.org/0000-0003-4111-4568)
Institutions
- Qinghai University (CN)
- University of the Punjab (PK)
- Capital Medical University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Peking Union Medical College Hospital (CN)
- Czech Academy of Sciences, Institute of Biotechnology (CZ)
- Center for Children (US)
- Institute of Molecular Genetics (RU)
- Research Center for Eco-Environmental Sciences (CN)
- Beijing Children’s Hospital (CN)
- Respiratory Clinical Trials (AU)
- State Key Laboratory of Respiratory Disease (CN)
Publication Details
- Journal
- Journal of Natural Products
- Published
- 2024-11-19
- DOI
- https://doi.org/10.1021/acs.jnatprod.4c00860
- Citations
- 1
- Primary Topic
- Microbial Natural Products and Biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 0.45
Funders
- National Natural Science Foundation of China
- Ministry of Science and Technology of the People's Republic of China
- Chinese Academy of Medical Sciences
- State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University
- Beijing Municipal Natural Science Foundation