Discovery of Oxidized Polycyclic Tetramate Macrolactams Bearing One or Two Rings through Combinatorial Pathway Reassembly
Organic Letters(2022)
摘要
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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