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 language | English |
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Pages (from-to) | 1633-1642 |
Number of pages | 10 |
Journal | Chemistry and Biology |
Volume | 22 |
Issue number | 12 |
DOIs | |
Publication status | Published - 17 Dec 2015 |
Keywords
- P450 enzyme
- biosynthesis
- carbazole alkaloids
- neocarazostatin A
- prenyltransferase
- reconstitution