Enzymatic formation of a prenyl β-carboline by a fungal indole prenyltransferase

Sherif Ahmed Hamdy; Takeshi Kodama; Yu Nakashima; Xiaojie Han; Takashi Matsui; Hiroyuki Morita

doi:10.1007/s11418-022-01635-0

Enzymatic formation of a prenyl β-carboline by a fungal indole prenyltransferase

Sherif Ahmed Hamdy, Takeshi Kodama, Yu Nakashima, Xiaojie Han, Takashi Matsui, Hiroyuki Morita^*

^*Corresponding author for this work

Section of Natural Products & Drug Discovery, Division of Medicinal Resources, Institute of Natural Medicine

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

3 Scopus citations

Abstract

CdpNPT from Aspergillus fumigatus is a fungal indole prenyltransferase (IPT) with remarkable substrate promiscuity to generate prenylated compounds. Our first investigation of the catalytic potential of CdpNPT against a β-carboline, harmol (1), revealed that the enzyme also accepts 1 as the prenyl acceptor with dimethylallyl diphosphate (DMAPP) as the prenyl donor and selectively prenylates the C-6 position of 1 by the “regular-type” dimethylallylation to produce 6-(3-dimethylallyl)harmol (2). Furthermore, our X-ray crystal structure analysis of the C-His₆-tagged CdpNPT (38-440) truncated mutant complexed with 1 and docking studies of DMAPP to the crystal structure of the CdpNPT (38-440) mutant suggested that CdpNPT could employ the two-step prenylation system to produce 2.

Original language	English
Pages (from-to)	873-879
Number of pages	7
Journal	Natural Medicines
Volume	76
Issue number	4
DOIs	https://doi.org/10.1007/s11418-022-01635-0
State	Published - 2022/09

Keywords

Harmol
Indole prenyltransferase
Prenylation
β-Carboline

ASJC Scopus subject areas

Pharmaceutical Science
Drug Discovery
Complementary and alternative medicine
Organic Chemistry

Access to Document

10.1007/s11418-022-01635-0

Cite this

@article{78cabdb57a9b4917a3582193e673f1f7,

title = "Enzymatic formation of a prenyl β-carboline by a fungal indole prenyltransferase",

abstract = "CdpNPT from Aspergillus fumigatus is a fungal indole prenyltransferase (IPT) with remarkable substrate promiscuity to generate prenylated compounds. Our first investigation of the catalytic potential of CdpNPT against a β-carboline, harmol (1), revealed that the enzyme also accepts 1 as the prenyl acceptor with dimethylallyl diphosphate (DMAPP) as the prenyl donor and selectively prenylates the C-6 position of 1 by the “regular-type” dimethylallylation to produce 6-(3-dimethylallyl)harmol (2). Furthermore, our X-ray crystal structure analysis of the C-His6-tagged CdpNPT (38-440) truncated mutant complexed with 1 and docking studies of DMAPP to the crystal structure of the CdpNPT (38-440) mutant suggested that CdpNPT could employ the two-step prenylation system to produce 2.",

keywords = "Harmol, Indole prenyltransferase, Prenylation, β-Carboline",

author = "Hamdy, {Sherif Ahmed} and Takeshi Kodama and Yu Nakashima and Xiaojie Han and Takashi Matsui and Hiroyuki Morita",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.",

year = "2022",

month = sep,

doi = "10.1007/s11418-022-01635-0",

language = "英語",

volume = "76",

pages = "873--879",

journal = "Natural Medicines",

issn = "1340-3443",

publisher = "Springer Japan",

number = "4",

}

TY - JOUR

T1 - Enzymatic formation of a prenyl β-carboline by a fungal indole prenyltransferase

AU - Hamdy, Sherif Ahmed

AU - Kodama, Takeshi

AU - Nakashima, Yu

AU - Han, Xiaojie

AU - Matsui, Takashi

AU - Morita, Hiroyuki

PY - 2022/9

Y1 - 2022/9

N2 - CdpNPT from Aspergillus fumigatus is a fungal indole prenyltransferase (IPT) with remarkable substrate promiscuity to generate prenylated compounds. Our first investigation of the catalytic potential of CdpNPT against a β-carboline, harmol (1), revealed that the enzyme also accepts 1 as the prenyl acceptor with dimethylallyl diphosphate (DMAPP) as the prenyl donor and selectively prenylates the C-6 position of 1 by the “regular-type” dimethylallylation to produce 6-(3-dimethylallyl)harmol (2). Furthermore, our X-ray crystal structure analysis of the C-His6-tagged CdpNPT (38-440) truncated mutant complexed with 1 and docking studies of DMAPP to the crystal structure of the CdpNPT (38-440) mutant suggested that CdpNPT could employ the two-step prenylation system to produce 2.

AB - CdpNPT from Aspergillus fumigatus is a fungal indole prenyltransferase (IPT) with remarkable substrate promiscuity to generate prenylated compounds. Our first investigation of the catalytic potential of CdpNPT against a β-carboline, harmol (1), revealed that the enzyme also accepts 1 as the prenyl acceptor with dimethylallyl diphosphate (DMAPP) as the prenyl donor and selectively prenylates the C-6 position of 1 by the “regular-type” dimethylallylation to produce 6-(3-dimethylallyl)harmol (2). Furthermore, our X-ray crystal structure analysis of the C-His6-tagged CdpNPT (38-440) truncated mutant complexed with 1 and docking studies of DMAPP to the crystal structure of the CdpNPT (38-440) mutant suggested that CdpNPT could employ the two-step prenylation system to produce 2.

KW - Harmol

KW - Indole prenyltransferase

KW - Prenylation

KW - β-Carboline

UR - http://www.scopus.com/inward/record.url?scp=85133160474&partnerID=8YFLogxK

U2 - 10.1007/s11418-022-01635-0

DO - 10.1007/s11418-022-01635-0

M3 - 学術論文

C2 - 35767141

AN - SCOPUS:85133160474

SN - 1340-3443

VL - 76

SP - 873

EP - 879

JO - Natural Medicines

JF - Natural Medicines

IS - 4

ER -

Enzymatic formation of a prenyl β-carboline by a fungal indole prenyltransferase

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Fingerprint

Cite this