The Evolutionary Pattern of Cocaine and Hyoscyamine Biosynthesis Provides Strategies To Produce Tropane Alkaloids

被引:1
作者
Zamar, Duchesse-Lacours [1 ]
Papon, Nicolas [2 ]
Courdavault, Vincent [1 ]
机构
[1] Univ Tours, Fac Pharm, EA2106 Biomol & Biotechnol Vegetales, 31 Ave Monge, F-37200 Tours, France
[2] Univ Angers, Univ Hosp Angers, Fungal Resp Infect Res Unit, 4 Rue Larrey, F-49933 Angers 09, France
关键词
evolution; tropane alkaloids; solanaceae; erythroxylaceae; metabolic engineering; STEP;
D O I
10.1002/cbic.202300234
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cocaine and hyoscyamine are two tropane alkaloids (TA) from Erythroxylaceae and Solanaceae, respectively. These famous compounds possess anticholinergic properties that can be used to treat neuromuscular disorders. While the hyoscyamine biosynthetic pathway has been fully elucidated allowing its de novo synthesis in yeast, the cocaine pathway remained only partially elucidated. Recently, the Huang research group has completed the cocaine biosynthetic route by characterizing its two missing enzymes. This allowed the whole pathway to be transferring into Nicotiana benthamiana to achieve cocaine production. Here, besides highlighting the impact of this discovery, we discuss how TA biosynthesis evolved via the recruitment of two distinct and convergent pathways in Erythroxylaceae and Solanaceae. Finally, while enriching our knowledge on TA biosynthesis, this diversification of the molecular actors involved in cocaine and hyoscyamine biosynthesis opens perspectives in metabolic engineering by exploring enzyme biochemical plasticity that can ease and shorten TA pathway reconstitution in heterologous organisms.
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页数:3
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