Overexpression of Global Regulator ShCrp Leads to the Discovery of Polycyclic Tetramate Macrolactams in <i>Streptomyces hebeiensis</i> HDN10-293
Two new polycyclic tetramate macrolactams (PTMs), shebamides A and B (1 and 2), were isolated from Streptomyces hebeiensis HDN10-293 following the activation of cryptic biosynthetic gene clusters by overexpression of the global regulator Crp. Their structures were elucidated via comprehensive spectroscopic analysis and electronic circular dichroism calculations, revealing a C-30 ketone─an oxidative modification rarely observed in the PTMs. Compound 1 exhibited significant cytotoxicity against 4 human cancer cell lines (IC50 6.45–12.30 μM). Their biosynthetic pathway was further proposed through functional gene cluster comparison. This study underscores the efficacy of global regulation-based genome mining for discovering structurally unique metabolites.
Authors
- Chuanteng Ma (ORCID: https://orcid.org/0000-0002-0262-8825)
- Xi Zhang (ORCID: https://orcid.org/0000-0002-4638-3997)
- Ruojin Liu
- Yueling Teng
- Tianjiao Zhu (ORCID: https://orcid.org/0000-0003-4185-5593)
- Dehai Li (ORCID: https://orcid.org/0000-0002-7191-2002)
- Wenxue Wang (ORCID: https://orcid.org/0000-0002-3469-1765)
- Qian Che (ORCID: https://orcid.org/0000-0003-0610-1593)
Institutions
- East China University of Science and Technology (CN)
- Institute of Marine Biotechnology (DE)
- Qingdao National Laboratory for Marine Science and Technology (CN)
- Qingdao Institute of Marine Geology (CN)
- Zubov State Oceanographic Institute (RU)
- Ocean University of China (CN)
Publication Details
- Journal
- Journal of Natural Products
- Published
- 2026-05-18
- DOI
- https://doi.org/10.1021/acs.jnatprod.6c00138
- Primary Topic
- Microbial Natural Products and Biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Key Research and Development Project of Hainan Province
- National Key Research and Development Program of China
- Fundamental Research Funds for the Central Universities