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 & Biology |
Volume | 22 |
Issue number | 12 |
Early online date | 3 Dec 2015 |
DOIs | |
Publication status | Published - 17 Dec 2015 |
Bibliographical note
AcknowledgmentsY.Y. acknowledges the financial support from “973” Program (2012CB721006) and National Natural Science Foundation of China (31570033). R.E., K.K., H.D., and M.J. acknowledge the financial support of the Leverhulme Trust-Royal Society Africa Award (AA090088).
Keywords
- carbazole alkaloids
- biosynthesis
- prenyltransferase
- reconstitution
- P450 enzyme
- neocarazostatin A