دورية
Expression of the Clifednamide Biosynthetic Pathway in StreptomycesGenerates 27,28-seco-Derivatives
| العنوان: | Expression of the Clifednamide Biosynthetic Pathway in StreptomycesGenerates 27,28-seco-Derivatives |
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| المؤلفون: | Jiao, Yu-Jie, Liu, Yan, Wang, Hao-Xin, Zhu, De-Yu, Shen, Yue-Mao, Li, Yao-Yao |
| المصدر: | Journal of Natural Products; September 2020, Vol. 83 Issue: 9 p2803-2808, 6p |
| مستخلص: | Polycyclic tetramate macrolactams (PoTeMs) are a group of hybrid PK-NRP natural products having a variable set of carbocyclic rings, a conserved assembly pathway, and diverse bioactivities. We report here the identification of seven new PoTeMs, clifednamides D–J (3–9), along with the known clifednamides A (1) and B (2) through rational pathway refactoring and heterologous expression. Remarkably, clifednamides D (3), G (6), and H (7) feature an unprecedented 27,28-secoskeleton. The cytotoxic activities of compounds 1–9indicated that the hydroxy group of C-25, the methyl group of C-30, the inner five-membered ring, and the intact macrocycle are all critical for the activities. Meanwhile, the cytochrome P450 enzyme CftS023A and the hydroxylase CftS023E involved in oxidative tailoring of clifednamides were found to decorate the fused 5–6 bicyclic intermediates. Accordingly, the biosynthetic pathway for clifednamides was proposed. |
| قاعدة البيانات: | Supplemental Index |
Find this issue from the American Chemical Society | تدمد: | 01633864 15206025 |
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| DOI: | 10.1021/acs.jnatprod.0c00900 |