Physiological and transcriptional characterization of Saccharomyces cerevisiae strains with modified expression of catabolic regulators

A comparative physiological and transcriptional study is presented on wild-type Saccharomyces cerevisiae and mutants with altered levels of catabolic regulators: hxk2Δ lacking hexokinase2, HAP4↑ overproducing hap4p and hxk2ΔHAP4↑. Relative to the wild-type, HAP4↑ showed the same growth rate with some increased yield on glucose, and hxk2Δ grew 28% slower but with a dramatically improved yield. Hxk2ΔHAP4↑ grew 14% slower but showed fully oxidative growth. A higher yield correlated with increased respiration. For both hxk2Δ strains, glucose repression was suppressed (upregulation of high-affinity sugar transporters, invertase and oxidative phosphorylation). T-profiler analysis showed that genes under control of the hap2/3/4/5-binding motif were significantly altered in expression in all strains. HAP4 overexpression, directly or in hxk2 knockouts, led to repression of the genes containing the Zap1p motif including ZAP1 itself, indicating altered zinc metabolism. Whereas HAP4 overexpression resulted in a shift towards oxidative metabolism only, deletion of HXK2 resulted in a strain that, in addition to being oxidative, almost completely lacked the ability to sense glucose. As the double mutant had an energy efficiency close to the maximum even with excess glucose and was derepressed to a larger extent and over a broader range, the functioning of the two regulators is in general considered to be additive.