Seminar - Retrobiosynthesis of natural and new-to-nature pharmaceuticals from non-standard amino acids

Sponsored by: The Department of Microbiology and Immunology

Please note that this seminar is scheduled for Zoom. Please register at: https://ubc.zoom.us/meeting/register/u5wtf-2prz4tGdekAVK9TKk9dBIL4nh7sn0N
 

Microbial synthesis, in which tractable laboratory microorganisms are engineered to produce high-value metabolites, overcomes many challenges facing crop-based manufacturing and total chemical synthesis. This talk highlights our recent efforts to build a yeast platform for high-level production of tetrahydroisoquinoline (THIQ) alkaloids, a diverse class of more than 3,000 plant metabolites. We leveraged our platform to produce near-commercial titers of opiates, a 100,000-fold improvement over previous efforts. We further showcased the biosynthetic potential of our production strain by synthesizing more than 10 THIQ scaffolds that have not been observed in nature.

Drawing from our work with opiates, I will outline a novel retrobiosynthesis approach to access untapped families of plant alkaloids and approved natural product drugs. These pharmaceuticals include the anti-hypotensive ephedrine (phenylpropylamino alkaloids), the anti-inflammatory colchicine (phenethylisoquinoline alkaloids), the anti-Alzheimer’s galantamine (Amaryllidaceae alkaloids), and the semi-synthetic solifenacin used to treat overactive bladder.A microbial source of plant pharmaceuticals will enable a more efficient, scalable, and reliable supply of these essential medicines, as well as the opportunity to synthesize new analogues for drug discovery.