Biosynthesis of Neocarazostatin A Reveals the Sequential Carbazole Prenylation and Hydroxylation in the Tailoring Steps. Issue 12 (17th December 2015)

• Record Type: Journal Article
• Authors: Huang, Sheng; Elsayed, Somayah Sameer; Lv, Meinan; Tabudravu, Jioji; Rateb, Mostafa E.; Gyampoh, Roland; Kyeremeh, Kwaku; Ebel, Rainer; Jaspars, Marcel; Deng, Zixin; Yu, Yi; Deng, Hai
• Is Part Of: Chemistry & biology. Volume 22:Issue 12(2015)
• Page Start: 1633
• Page End: 1642
• Publication Date: 2015-12-17
• Subjects: carbazole alkaloids -- biosynthesis -- prenyltransferase -- reconstitution -- P450 enzyme -- neocarazostatin A; Biochemistry -- Periodicals; 540
• DOI: 10.1016/j.chembiol.2015.10.012
• Languages: English
• ISSNs: 1074-5521

Abstract

Summary: 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. Graphical Abstract: Highlights: The biosynthetic gene cluster of neocarazostatin A was identified A new type of carbazole prenyltransferases, NzsG, was characterized The P450 enzyme NzsA catalyzing the last step of the biosynthesis was identified The biotransformation in the late stage of the biosynthesis was reconstituted Abstract : Huang et al. identified the gene cluster directing the biosynthesis of neocarazostatin A, characterized two new enzymes responsible for the late stage of the biosynthesis, and reconstituted in vitro the biotransformation from the biosynthetic intermediate to neocarazostatin A.