Due to a growing market for the biodegradable and renewable polymer polylactic acid, the world demand for lactic acid is rapidly increasing.  However, lactic acid toxicity at high concentrations or low pH (as required for the production of free acid) is a major concern in the industrial production of lactic acid, where very high concentrations of free lactic acid are desired.  Saccharomyces cerevisiae is the most well characterized eukaryote, the preferred microbial cell factory for the largest industrial biotechnology product (bioethanol), and a robust commercially compatible scaffold to be exploited for diverse chemical production.  S. cerevisiae has also been explored as a host for lactic acid production because of its high acid tolerance.  Here we developed L-lactic acid-overproducing S. cerevisiae by redirecting cellular carbon flux into the production of L-lactic acid.  To this end, we deleted the genes that encode pyruvate decarboxylase 1 (PDC1), L-lactate cytochrome-c oxidoreductase (CYB2) and glycerol-3-phosphate dedydrogenase (GPD1) by replacing them with a heterologous L-lactate dehydrogenase gene (L-LDH) in S. cerevisiae.  To further increase L-lactic acid production, glycolytic flux was improved, which increased the availability of a precursor of L-lactic acid.  The resulting strain, called SAIT-LA, showed a high carbon flux towards L-lactic acid production with L-lactic acid productivity of 2 g/L/h in a glucose fed-batch bioreactor.  This result demonstrates that the L-lactic acid-overproducing S. cerevisiae can be achieved through the redirection of the overflowed carbon metabolism, most likely by increasing the carbon availability and improving the redox balance.

Enhanced production of L-lactic acid by redirecting carbon fluxes in <i>Saccharomyces cerevisiae   </i>

246th National Meeting (2013)

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Enhanced production of L-lactic acid by redirecting carbon fluxes in Saccharomyces cerevisiae