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 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 Rateb, Roland Gyampoh, Kwaku Kyeremeh, Rainer Ebel, Marcel Jaspars, Zixin Deng, Yi Yu, Hai Deng

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34 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
Journal	Chemistry & Biology
Volume	22
Issue number	12
DOIs	https://doi.org/10.1016/j.chembiol.2015.10.012
Publication status	Published - 17 Dec 2015
Externally published	Yes

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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. ",

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

year = "2015",

month = dec,

day = "17",

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

language = "English",

volume = "22",

pages = "1633--1642",

journal = "Chemistry \& Biology",

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publisher = "Elsevier Inc.",

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TY - JOUR

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

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.

U2 - 10.1016/j.chembiol.2015.10.012

DO - 10.1016/j.chembiol.2015.10.012

M3 - Article

SN - 1074-5521

VL - 22

SP - 1633

EP - 1642

JO - Chemistry & Biology

JF - Chemistry & Biology

IS - 12

ER -

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

Abstract

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