Discovery of Oxidized Polycyclic Tetramate Macrolactams Bearing One or Two Rings through Combinatorial Pathway Reassembly

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 Streptornyces. 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.

Automated summary

The structural diversity of PoTeMs is mainly generated by cyclases and cytochrome P450s. In Saccharopolyspora hirsuta, six new cytotoxic PoTeMs, including the first examples of oxidized one-ring PoTeMs, were discovered through combinatorial reassembling and heterologous expression.