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 E 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
Number of pages10
JournalChemistry & Biology
Volume22
Issue number12
Early online date3 Dec 2015
DOIs
Publication statusPublished - 17 Dec 2015

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Prenylation
Hydroxylation
Biosynthesis
Dimethylallyltranstransferase
Genes
Biosynthetic Pathways
Gene Silencing
Mixed Function Oxygenases
Bioactivity
Alkaloids
Free Radicals
Assays
Genome
Enzymes
neocarazostatin A
carbazole
Experiments
In Vitro Techniques

Keywords

  • carbazole alkaloids
  • biosynthesis
  • prenyltransferase
  • reconstitution
  • P450 enzyme
  • neocarazostatin A

Cite this

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

In: Chemistry & Biology, Vol. 22, No. 12, 17.12.2015, p. 1633-1642.

Research output: Contribution to journalArticle

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. / Biosynthesis of neocarazostatin A reveals the sequential carbazole prenylation and hydroxylation in the tailoring steps. In: Chemistry & Biology. 2015 ; Vol. 22, No. 12. pp. 1633-1642.
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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.",
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AB - 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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