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

doi:10.1016/j.chembiol.2015.10.012

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

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

39 Citations (Scopus)

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
Pages (from-to)	1633-1642
Number of pages	10
Journal	Chemistry and Biology
Volume	22
Issue number	12
DOIs	https://doi.org/10.1016/j.chembiol.2015.10.012
Publication status	Published - 17 Dec 2015

Keywords

P450 enzyme
biosynthesis
carbazole alkaloids
neocarazostatin A
prenyltransferase
reconstitution

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10.1016/j.chembiol.2015.10.012

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title = "Biosynthesis of Neocarazostatin A Reveals the Sequential Carbazole Prenylation and Hydroxylation in the Tailoring Steps",

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.",

keywords = "P450 enzyme, biosynthesis, carbazole alkaloids, neocarazostatin A, prenyltransferase, reconstitution",

author = "Sheng Huang and Elsayed, \{Somayah Sameer\} and Meinan Lv and Jioji Tabudravu and Rateb, \{Mostafa E.\} and Roland Gyampoh and Kwaku Kyeremeh and Rainer Ebel and Marcel Jaspars and Zixin Deng and Yi Yu and Hai Deng",

year = "2015",

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day = "17",

doi = "10.1016/j.chembiol.2015.10.012",

language = "English",

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journal = "Chemistry and Biology",

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T1 - Biosynthesis of Neocarazostatin A Reveals the Sequential Carbazole Prenylation and Hydroxylation in the Tailoring Steps

AU - Huang, Sheng

AU - Elsayed, Somayah Sameer

AU - Lv, Meinan

AU - Tabudravu, Jioji

AU - Rateb, Mostafa E.

AU - Gyampoh, Roland

AU - Kyeremeh, Kwaku

AU - Ebel, Rainer

AU - Jaspars, Marcel

AU - Deng, Zixin

AU - Yu, Yi

AU - Deng, Hai

PY - 2015/12/17

Y1 - 2015/12/17

N2 - 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.

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.

KW - P450 enzyme

KW - biosynthesis

KW - carbazole alkaloids

KW - neocarazostatin A

KW - prenyltransferase

KW - reconstitution

UR - https://www.scopus.com/pages/publications/84950301578

U2 - 10.1016/j.chembiol.2015.10.012

DO - 10.1016/j.chembiol.2015.10.012

M3 - Article

C2 - 26670080

AN - SCOPUS:84950301578

SN - 1074-5521

VL - 22

SP - 1633

EP - 1642

JO - Chemistry and Biology

JF - Chemistry and Biology

IS - 12

ER -

Biosynthesis of Neocarazostatin A Reveals the Sequential Carbazole Prenylation and Hydroxylation in the Tailoring Steps

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Keywords

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