Discovery and Engineering of the Cocaine Biosynthetic Pathway
文献类型：期刊论文
| 作者 | Wang, Yong-Jiang; Huang, Jian-Ping; Tian, Tian; Yan, Yijun; Chen, Yin; Yang, Jing ; Chen, Jianghua; Gu, Yu-Cheng; Huang, Sheng-Xiong
|
| 刊名 | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
 |
| 出版日期 | 2022 |
| 关键词 | TROPANE ALKALOID BIOSYNTHESIS ERYTHROXYLUM COCA METHYLATION STEP |
| DOI | 10.1021/jacs.2c09091 |
| 英文摘要 | Cocaine, the archetypal tropane alkaloid from the plant genus Erythroxylum, has recently been used clinically as a topical anesthesia of the mucous membranes. Despite this, the key biosynthetic step of the requisite tropane skeleton (methylecgonone) from the identified inter -mediate 4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoic acid (MPOA) has remained, until this point, unknown. Herein, we identify two missing enzymes (EnCYP81AN15 and EnMT4) necessary for the biosynthesis of the tropane skeleton in cocaine by transient expression of the candidate genes in Nicotiana benthamiana. Cytochrome P450 EnCYP81AN15 was observed to selectively mediate the oxidative cyclization of S-MPOA to yield the unstable intermediate ecgonone, which was then methylated to form optically active methylecgonone by methyltransferase EnMT4 in Erythrox-ylum novogranatense. The establishment of this pathway corrects the long-standing (but incorrect) biosynthetic hypothesis of MPOA methylation first and oxidative cyclization second. Notably, the de novo reconstruction of cocaine was realized in N. benthamiana with the two newly identified genes, as well as four already known ones. This study not only reports a near-complete biosynthetic pathway of cocaine and provides new insights into the metabolic networks of tropane alkaloids (cocaine and hyoscyamine) in plants but also enables the heterologous synthesis of tropane alkaloids in other (micro)organisms, entailing significant implications for pharmaceutical production. |
| WOS记录号 | WOS:000885931600001 |
| 源URL | [http://ir.kib.ac.cn/handle/151853/75663]  |
| 专题 | 中国科学院昆明植物研究所 |
| 推荐引用方式 GB/T 7714 | Wang, Yong-Jiang,Huang, Jian-Ping,Tian, Tian,et al. Discovery and Engineering of the Cocaine Biosynthetic Pathway[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2022. |
| APA | Wang, Yong-Jiang.,Huang, Jian-Ping.,Tian, Tian.,Yan, Yijun.,Chen, Yin.,...&Huang, Sheng-Xiong.(2022).Discovery and Engineering of the Cocaine Biosynthetic Pathway.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. |
| MLA | Wang, Yong-Jiang,et al."Discovery and Engineering of the Cocaine Biosynthetic Pathway".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2022). |
入库方式： OAI收割
来源：昆明植物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。