Back to the plant: overcoming roadblocks to the microbial production of pharmaceutically important plant natural products

Microbial fermentation platforms offer a cost-effective and sustainable alternative to plant cultivation and chemical synthesis for the production of many plant-derived pharmaceuticals. Plant alkaloids, particularly benzylisoquinoline alkaloids and monoterpene indole alkaloids, and recently cannabinoids have become attractive targets for microbial biosynthesis owing to their medicinal importance. Recent advances in the discovery of pathway components, together with the application of synthetic biology tools, have facilitated the assembly of plant alkaloid and cannabinoid pathways in the microbial hosts Escherichia coli and Saccharomyces cerevisiae. This review highlights key aspects of these pathways in the framework of overcoming bottlenecks in microbial production to further improve end-product titers. We discuss the opportunities that emerge from a better understanding of the pathway components by further study of the plant, and strategies for generation of new and advanced medicinal compounds.