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Compartmentalization strategies for engineered metabolic pathways
John E. Dueber, University of California, Berkeley, USA
My lab is endeavoring to construct the upstream part of the benzylisoquinoline alkaloid
(BIA) pathway in Saccharomyces cerevisiae. This pathway suffers from a step that
condenses two substrates, one of which is highly reactive and likely a substrate for one
or more endogenous yeast enzymes and the other secreted. As a potential solution to
this problem, we are repurposing an organelle for compartmentalizing the engineered
BIA pathway to insulate it from the rest of the cellular milieu via a lipid bilayer
membrane. In this manner, we aim to concentrate the reactive intermediates to
productively condense in the organelle before undesired cross-reactions can occur in
the cytosol. In this talk, I will discuss efforts in both areas towards our ultimate goal of
high flux through the top part of the BIA pathway in S. cerevisiae.