Samuel A Bradley, Frederik G Hansson, Beata J Lehka, Daniela Rago, Pedro Pinho, Huadong Peng, Khem B Adhikari, Ahmad K Haidar, Lea G Hansen, Daria Volkova, Maxence Holtz, Sergi Muyo Abad, Xin Ma, Konstantinos Koudounas, Sébastien Besseau, Nicolas Gautron, Céline Mélin, Jillian Marc, Caroline Birer Williams, Vincent Courdavault, Emil D Jensen, Jay D Keasling, Jie Zhang, Michael K Jensen
Monoterpene indole alkaloids (MIAs) make up a highly bioactive class of metabolites produced by a range of tropical and subtropical plants. The corynanthe-type MIAs are a stereochemically complex subclass with therapeutic potential against a large number of indications including cancer, psychotic disorders, and erectile dysfunction. Here, we report yeast-based cell factories capable of de novo production of corynanthe-type MIAs rauwolscine, yohimbine, tetrahydroalstonine, and corynanthine. From this, we demonstrate regioselective biosynthesis of 4 fluorinated derivatives of these compounds and de novo biosynthesis of 7-chlororauwolscine by coexpression of a halogenase with the biosynthetic pathway...
April 18, 2024: ACS Synthetic Biology