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Updated: Aug 30, 2025
From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
Discovery of Oxidized Polycyclic Tetramate Macrolactams Bearing One or Two Rings through Combinatorial Pathway
Haochen Zou1, Xin Xia1, Qiushuang Xu2
1Key Laboratory of Chemical Biology of Ministry of Education, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
Abstract:
The structural diversity of polycyclic tetramate macrolactams (PoTeMs) are mainly generated by the cyclases and cytochrome P450s (CYPs). The PoTeM cluster sah in Saccharopolyspora hirsuta harboring two CYP genes was combinatorially reassembled and heterologously expressed in Streptomyces. As a result, six new cytotoxic PoTeMs, sahamides A-F (1-6), were discovered, and 1-3 are the first examples of oxidized one-ring PoTeMs. Remarkably, SahE represents the first CYP performing oxidative modification on the ornithine moiety of PoTeMs.
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