Functional characterization of CYP81C16 involved in the tanshinone biosynthetic pathway in Salvia miltiorrhiza.
10.1016/S1875-5364(23)60484-4
- Author:
Li REN
1
;
Linglong LUO
1
;
Zhimin HU
1
;
Ying MA
1
;
Jian WANG
1
;
Yatian CHENG
1
;
Baolong JIN
1
;
Tong CHEN
1
;
Jinfu TANG
1
;
Guanghong CUI
1
;
Juan GUO
2
;
Luqi HUANG
3
Author Information
1. State Key Laboratory of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100000, China.
2. State Key Laboratory of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100000, China. Electronic address: guojuanzy@163.com.
3. State Key Laboratory of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100000, China. Electronic address: huangluqi01@126.com.
- Publication Type:Journal Article
- Keywords:
Biosynthetic pathway;
Cytochrome P450;
Hydroxylation;
Neocryptotanshinone;
Salvia miltiorrhiza;
Tanshinone
- MeSH:
Humans;
Salvia miltiorrhiza/metabolism*;
Biosynthetic Pathways;
Quinones/metabolism*;
Plant Roots/metabolism*;
Gene Expression Regulation, Plant
- From:
Chinese Journal of Natural Medicines (English Ed.)
2023;21(12):938-949
- CountryChina
- Language:English
-
Abstract:
Danshen, the dried roots and rhizomes of Salvia miltiorrhiza Bunge (S. miltiorrhiza), is widely used in the treatment of cardiovascular and cerebrovascular diseases. Tanshinones, the bioactive compounds from Danshen, exhibit a wide spectrum of pharmacological properties, suggesting their potential for future therapeutic applications. Tanshinone biosynthesis is a complex process involving at least six P450 enzymes that have been identified and characterized, most of which belong to the CYP76 and CYP71 families. In this study, CYP81C16, a member of the CYP71 clan, was identified in S. miltiorrhiza. An in vitro assay revealed that it could catalyze the hydroxylation of four para-quinone-type tanshinones, namely neocryptotanshinone, deoxyneocryptotanshinone, and danshenxinkuns A and B. SmCYP81C16 emerged as a potential broad-spectrum oxidase targeting the C-18 position of para-quinone-type tanshinones with an impressive relative conversion rate exceeding 90%. Kinetic evaluations andin vivo assays underscored its highest affinity towards neocryptotanshinone among the tested substrates. The overexpression of SmCYP81C16 promoted the accumulation of (iso)tanshinone in hairy root lines. The characterization of SmCYP81C16 in this study accentuates its potential as a pivotal tool in the biotechnological production of tanshinones, either through microbial or plant metabolic engineering.
