bioRxiv preprint doi: https://doi.org/10.1101/863506; this version posted December 5, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. A yeast platform for high-level synthesis of natural and unnatural tetrahydroisoquinoline alkaloids Michael E. Pyne a,b, Kaspar Kevvai a,b,*, Parbir S. Grewalc,*, Lauren Narcross a,b, Brian Choic, Leanne Bourgeois a,b, John E. Dueberd, & Vincent J. J. Martin a,b, a Department of Biology, Concordia University, Montréal, Québec, Canada b Centre for Applied Synthetic Biology, Concordia University, Montréal, Québec, Canada c Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, California, USA d Department of Bioengineering, University of California, Berkeley, Berkeley, California, USA * These authors contributed equally to this work Correspondence and requests for materials should be addressed to: Vincent J.J. Martin (email:
[email protected]) bioRxiv preprint doi: https://doi.org/10.1101/863506; this version posted December 5, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. ABSTRACT The tetrahydroisoquinoline (THIQ) moiety is a privileged substructure of many bioactive natural products and semi-synthetic analogues. The plant kingdom manufactures more than 3,000 THIQ alkaloids, including the opioids morphine and codeine.