A Modified Cre-lox Genetic Switch To Dynamically Control Metabolic Flow in Saccharomyces cerevisiae

The control of metabolic flow is a prerequisite for efficient chemical production in transgenic microorganisms. Exogenous genes required for the biosynthesis of target chemicals are expressed under strong promoters, while the endogenous genes of the original metabolic pathway are repressed by disruption or mutation. These genetic manipulations occasionally cause harmful effects to the host. In the lactate-producing yeast Saccharomyces cerevisiae, where endogenous pyruvate decarboxylase (PDC) is disrupted and exogenous lactate dehydrogenase (LDH) is introduced, PDC deletion is extremely detrimental to cell growth but is required for efficient production of lactate. A suitable means to dynamically control the metabolic flow from ethanol fermentation during the growth phase to lactate fermentation during the production phase is needed. Here, we demonstrated that this flow can be controlled by the exclusive expression of PDC and LDH with a Cre-lox genetic switch. This switch was evaluated with a gene cassette...