Journal
CHEMISTRY & BIOLOGY
Volume 22, Issue 12, Pages 1633-1642Publisher
CELL PRESS
DOI: 10.1016/j.chembiol.2015.10.012
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Funding
- 973 Program [2012CB721006]
- National Natural Science Foundation of China [31570033]
- Leverhulme Trust-Royal Society Africa Award [AA090088]
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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.
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