The GLO1 Gene Is Required for Full Activity of O‑Acetyl Homoserine Sulfhydrylase Encoded by MET17

• Published in: ACS chemical biology 2017-02, Vol.12 (2), p.414-421
• Main Authors: Kinzurik, Matias I, Ly, Kien, David, Karine M, Gardner, Richard C, Fedrizzi, Bruno
• Format: Article
• Language: English
• Subjects: Cysteine Synthase - genetics; Cysteine Synthase - metabolism; Fermentation; Gene Deletion; Genes, Fungal; Hydrogen Sulfide - metabolism; Lactoylglutathione Lyase - genetics; Mutation; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism
• ISSN: 1554-8929; 1554-8937
• DOI: 10.1021/acschembio.6b00815

During glycolysis, yeast generates methylglyoxal (MG), a toxic metabolite that affects growth. Detoxification can occur when glyoxylase I (GLO1) and glyoxylase II (GLO2) convert MG to lactic acid. We have identified an additional, previously unrecognized role for GLO1 in sulfur assimilation in the yeast Saccharomyces cerevisiae. During a screening for putative carbon–sulfur lyases, the glo1 deletion strain showed significant production of H2S during fermentation. The glo1 strain also assimilated sulfate inefficiently but grew normally on cysteine. These phenotypes are consistent with reduced activity of the O-acetyl homoserine sulfhydrylase, Met17p. Overexpression of Glo1p gave a dominant negative phenotype that mimicked the glo1 and met17 deletion strain phenotypes. Western analysis revealed reduced expression of Met17p in the glo1 deletion, but there was no indication of an altered conformation of Met17p or any direct interaction between the two proteins. Unravelling a novel function in sulfur assimilation and H2S generation in yeast for a gene never connected with this pathway provides new opportunities for the study of this molecule in cell signaling, as well as the potential regulation of its accumulation in the wine and beer industry.