Neocarazostatin A (NZS) is a bacterial alkaloid with promising bioactivities against free radicals, featuring a tricyclic carbazole nucleus with a prenyl moiety at C-6 of the carbazole ring. Here, we report the discovery and characterization of the biosynthetic pathway of NZS through genome mining and gene inactivation. The in vitro assays characterized two enzymes: NzsA is a P450 hydroxylase and NzsG is a new phytoene-synthase-like prenyltransferase (PTase). This is the first reported native PTase that specifically acts on the carbazole nucleus. Finally, our in vitro reconstituted experiment demonstrated a coupled reaction catalyzed by NzsG and NzsA tailoring the NZS biosynthesis.
- carbazole alkaloids
- P450 enzyme
- neocarazostatin A
Huang, S., Elsayed, S. S., Lv, M., Tabudravu, J., Rateb, M. E., Gyampoh, R., Kyeremeh, K., Ebel, R., Jaspars, M., Deng, Z., Yu, Y., & Deng, H. (2015). Biosynthesis of neocarazostatin A reveals the sequential carbazole prenylation and hydroxylation in the tailoring steps. Chemistry & Biology, 22(12), 1633-1642. https://doi.org/10.1016/j.chembiol.2015.10.012