A novel O-methyltransferase with substrate promiscuity from Ardisia japonica
10.16438/j.0513-4870.2022-1102
- VernacularTitle:紫金牛中一个新颖底物杂泛性O-甲基转移酶
- Author:
Qi LIU
1
;
Rui-qi YAN
1
;
Bing-han XIE
1
;
Song-yang SUI
2
,
3
;
Ke-bo XIE
2
,
3
;
Jun-gui DAI
2
,
3
;
Lin YANG
1
Author Information
1. College of Life and Environmental Sciences, Minzu University of China, Beijing 100081, China
2. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, CAMS Key Laboratory of Enzymes and Natural Drug Biocatalysis, NHC Key Laboratory of Natural Drug Biosynthesis, Institute of Materia Medica, Peking Union Medical College &
3. Chinese Academy of Medical Sciences, Beijing 100050, China
- Publication Type:Research Article
- Keywords:
italic>Ardisia japonica;
italic>O-methyltransferase;
italic>O-methylation;
substrate promiscuity;
regio-selectivity
- From:
Acta Pharmaceutica Sinica
2023;58(5):1372-1382
- CountryChina
- Language:Chinese
-
Abstract:
italic>O-methyltransferases (OMTs) are one of the key tailoring enzymes in the biosynthesis of many natural products, O-methylation can not only reduce the reactivity of natural products, but also alter their solubility, stability and biological activities. Based on the transcriptome data of Ardisia japonica, a full-length cDNA sequence of candidate OMT (termed as AjOMT1) was cloned by reverse transcription-polymerase chain reaction (RT-PCR) and expressed in Escherichia coli (E. coli) for the first time. In vitro enzyme catalytic activity assay showed that the recombinant AjOMT1 could effectively catalyze quercetin to form O-methylated products. Most importantly, AjOMT1 showed unprecedented substrate promiscuity towards structurally various compounds including flavonoids, stilbenes, coumarins, alkaloids and phenylpropanoids, especially preferring to the compounds with adjacent phenolic hydroxyl groups, and showed regio-selectivity. These results suggested that AjOMT1 could be used as the tool enzyme to conduct O-methylation of different types of compounds to produce diverse active methylated products, and provide a new method for drug discovery, even universal part for synthetic biology of natural products.
