title: Effects of metal ions and hydrogen peroxide on the phenotype of yeast hom6Δ mutant.
abstract: HOM6 is a major gene in the aspartate pathway which leads to biosynthesis of threonine and methionine. The phenotypes of the gene deletion mutant (hom6∆) in a variety of cultural conditions have previously provided meaningful insights into the biological roles of HOM6 and its upstream intermediate metabolites. Here, we conducted a survey on a spectrum of metal ions for their effect on the aspartate pathway and broader sulphur metabolism. We show that manganese (Mn(2+) ) promoted the growth of hom6∆ under both anaerobic and aerobic conditions. Unexpectedly, 4 mmol l(-1) hydrogen peroxide (H2 O2 ), a dose normally causing temporary cell growth arrest, enhanced the growth of hom6∆ under the anaerobic condition only, while it had no effect on the wild type strain BY4743. We propose that Mn(2+) and H2 O2 promote the growth of hom6∆ by reducing the accumulation of the toxic intermediate metabolite-aspartate β-semialdehyde, via directing the aspartate pathway to the central sugar metabolism-tricarboxylic acid cycle.
  
  
  CONCLUSIONS
  This study focuses on the yeast strain which lacks homoserine dehydrogenase encoded by HOM6 gene in aspartate metabolism. The HOM6-deletion mutant (hom6Δ) was analysed in the context of varying environmental parameters such as metal ions and oxidants, under anaerobic and aerobic conditions. We demonstrated that both manganese and hydrogen peroxide can promote the growth of hom6Δ, with the latter exerting such effect only under anaerobic condition. The findings are relevant to the research areas of ageing and anti-fungal drug development. It highlights the importance of interactions between gene expression and environmental factors as well as culture conditions.
authors.affiliation: School of Science and Health, University of Western Sydney, Penrith, NSW, Australia.
authors.forename: N M
authors.initials: NM
authors.lastname: Tun
authors.forename: B R
authors.initials: BR
authors.lastname: Lennon
authors.forename: P J
authors.initials: PJ
authors.lastname: O'Doherty
authors.forename: A J
authors.initials: AJ
authors.lastname: Johnson
authors.forename: G
authors.initials: G
authors.lastname: Petersingham
authors.forename: T D
authors.initials: TD
authors.lastname: Bailey
authors.forename: C
authors.initials: C
authors.lastname: Kersaitis
authors.forename: M J
authors.initials: MJ
authors.lastname: Wu
mesh_terms: D000332:Aerobiosis; D000693:Anaerobiosis; D001224:Aspartic Acid / Q000378:metabolism; D003470:Culture Media; D017353:Gene Deletion; D006715:Homoserine Dehydrogenase / Q000235:genetics*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008345:Manganese / Q000494:pharmacology*; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D008670:Metals / Q000494:pharmacology*; D009154:Mutation; D016877:Oxidants / Q000494:pharmacology; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics
chemical_list: D003470:Culture Media; D008670:Metals; D016877:Oxidants; D029701:Saccharomyces cerevisiae Proteins; D001224:Aspartic Acid; D008345:Manganese; D006861:Hydrogen Peroxide; D006715:Homoserine Dehydrogenase
keywords: HOM6 deletion; Saccharomyces cerevisiae; aspartate pathway; hydrogen peroxide; metal ions