Biosynthesis of neocarazostatin A reveals the sequential carbazole prenylation and hydroxylation in the tailoring steps

Sheng Huang, Somayah Sameer Elsayed, Meinan Lv, Jioji Tabudravu, Mostafa Rateb, Roland Gyampoh, Kwaku Kyeremeh, Rainer Ebel, Marcel Jaspars, Zixin Deng, Yi Yu, Hai Deng

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Abstract

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.

Original languageEnglish
Pages (from-to)1633-1642
JournalChemistry & Biology
Volume22
Issue number12
DOIs
Publication statusPublished - 17 Dec 2015
Externally publishedYes

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Huang, S., Elsayed, S. S., Lv, M., Tabudravu, J., Rateb, M., 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