2-30: Improved galactose fermentation by Saccharomyces cerevisiae through inverse metabolic engineering

Biomass from marine plants has several interesting attributes which make it a potential renewable source for production of biofuels.  In terms of mass per unit area, yields of marine biomass are higher than yields of terrestrial lignocellulosic biomass.  Marine biomass does not contain recalcitrant lignin or crystalline cellulose and is therefore depolymerized more easily than lignocellulosic biomass.  Relatively high rates of carbon fixation by marine plants also make them attractive for carbon dioxide sequestration and recycling.  One of the abundant carbohydrates in marine biomass is galactose. Although Saccharomyces cerevisiae is capable of fermenting galactose into ethanol, ethanol yield and productivity from galactose are significantly lower than those from glucose. An inverse metabolic engineering approach was undertaken to improve ethanol yield and productivity from galactose in S. cerevisiae. Specifically, we introduced a genome-wide perturbation library into S. cerevisiae, and then screened fast galactose-fermenting transformants. Characterization of genetic perturbations in the isolated transformants revealed novel targets which elicit enhanced galactose utilization in yeast. Interestingly, most of them are not directly related to galactose metabolism. Of the identified genetic perturbations, overexpression of a well-known transcriptional regulator in a truncated form drastically increased ethanol yield and productivity from galactose as well as from a mixture of glucose and galactose. These results suggest that global reconfiguration of sugar metabolism is more effective than overexpression of a single metabolic gene in the galactose assimilation pathway for efficient galactose fermentation in S. cerevisiae.