FEMS Microbiology Letters 106 (1993) 233-238 © 1993 Federation of European Microbiological Societies 0378-1097/93/$06.00 Published by Elsevier 233 FEMSLE 05242 Characterization of mutations that overcome the toxic effect of glucose on phosphoglucose isomerase less strains of Saccharomyces cerevisiae Francisco-Javier Gamo, Francisco Portillo and Carlos Gancedo Instituto de Investigaciones Biomddicas C.S.L C., Facultad de Medicina U.A.M., Madrid, Spain (Received 13 October 1992; revision received 29 October 1992; accepted 30 October 1992) Abstract: Glucose inhibits growth of yeast phosphoglucose isomerase mutants in permissive media. Mutants insensitive to this effect were isolated by selection on media containing 2% fructose + 2% glucose. A nuclear, monogenic, recessive mutation named rgl was responsible for this phenotype. The mutants isolated belonged to two complementation groups and have been termed rgll and rgl2. When the double mutants were grown on fructose, fermentation of fructose or glucose was similar to that of the parental pgi strain but was not measurable when grown on fructose + glucose. Under these conditions, respiration of glucose and to a lesser extent of fructose was enhanced. The double mutants pgi rgl did not grow on fructose + glucose in the presence of antimycin A or ethidium bromide and their cytochrome oxidase was no longer sensitive to glucose repression. The results are interpreted as an indication that in the double mutants the glucose may be channeled through the pentose phosphate pathway to respiration. Key words: Phosphoglucose isomerase; Glucose toxicity; Saccharomyces; Glycolysis Introduction Yeast mutants blocked in any of the steps of the glycolytic pathway do not grow on glucose; moreover, glucose produces an inhibition of growth on other permissive carbon sources [1,2]. This effect has been particularly well documented in the case of mutants lacking phosphoglucose isomerase (pgi). While Escherichia coli mutants affected in the phosphoglucose isomerase step grow on glucose through the pentose phosphate Correspondence to: C. Gancedo, Instituto de Investigaciones Biom6dicas, C/Arturo Duperier 4, E-28029 Madrid, Spain. pathway [3], yeast mutants affected in the same step do not grow on glucose [4-6]. These mutants grow on rich media with fructose or ethanol as carbon sources, but addition of small amounts of glucose arrests growth without affecting viability [2,4]. Addition of glucose to yeast pgi mutants produces accumulation of glucose-6-phosphate and a decrease in ATP content [2,4,7]. Although these metabolic effects were believed to be the cause of growth inhibition, the physiological basis of this inhibition remains unclear. A possible way to understand the inhibitory mechanism(s) of glu- cose is to study mutants in which this sugar is no longer inhibitory. Aguilera [6] isolated in a pgi background mutants able to grow on mixtures of Downloaded from https://academic.oup.com/femsle/article/106/3/233/516548 by guest on 29 March 2023