Enhanced productivity through gratuitous induction in recombinant yeast fermentations

The advantages of gratuitous induction for GAL-regulated cloned gene (lacZ) product synthesis were evaluated for the yeast Saccharomyces cerevisiae. The growth, yield, and productivity of a gratuitous (gal1) strain were compared with those of an otherwise isogenic, nongratuitous (GAL1) strain. Batch studies clearly demonstrated the improvements possible in product synthesis when the inducer is not metabolized by the yeast cells; both beta-galactosidase specific and volumetric activities were superior for the gal1 strain. At equivalent metabolizable sugar concentrations, the productivity of the gratuitous strain exceeded that of the nongratuitous strain by 180%. The effects of initial inducer concentration and induction time were also examined. For the gratuitous strain, galactose:glucose ratios as low as 0.1 still gave maximum beta-galactosidase volumetric activity. A 5-fold higher ratio was necessary for full induction with the nongratuitous strain, and productivity was substantially lower relative to the gal1 strain. A comparison of various times for galactose addition indicated that productivity is highest when the gratuitous culture is induced for the entire batch fermentation.