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^* (Corresponding Author), Hai Deng^* (Corresponding Author)

^*Corresponding author for this work

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

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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 language	English
Pages (from-to)	1633-1642
Number of pages	10
Journal	Chemistry & Biology
Volume	22
Issue number	12
Early online date	3 Dec 2015
DOIs	https://doi.org/10.1016/j.chembiol.2015.10.012
Publication status	Published - 17 Dec 2015

Keywords

carbazole alkaloids
biosynthesis
prenyltransferase
reconstitution
P450 enzyme
neocarazostatin A

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Hai Deng
- School of Natural & Computing Sciences, Chemistry - Reader
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@article{f9cce7df47da4f8284e684096e13ae81,

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

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",

note = "Acknowledgments Y.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).",

year = "2015",

month = dec,

day = "17",

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

language = "English",

volume = "22",

pages = "1633--1642",

journal = "Chemistry & Biology",

issn = "1074-5521",

publisher = "Elsevier Inc.",

number = "12",

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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 E

AU - Gyampoh, Roland

AU - Kyeremeh, Kwaku

AU - Ebel, Rainer

AU - Jaspars, Marcel

AU - Deng, Zixin

AU - Yu, Yi

AU - Deng, Hai

N1 - Acknowledgments Y.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).

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 - carbazole alkaloids

KW - biosynthesis

KW - prenyltransferase

KW - reconstitution

KW - P450 enzyme

KW - neocarazostatin A

U2 - 10.1016/j.chembiol.2015.10.012

DO - 10.1016/j.chembiol.2015.10.012

M3 - Article

VL - 22

SP - 1633

EP - 1642

JO - Chemistry & Biology

JF - Chemistry & Biology

SN - 1074-5521

IS - 12

ER -

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

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