title: Disruption of multiple genes whose deletion causes lactic-acid resistance improves lactic-acid resistance and productivity in Saccharomyces cerevisiae.
abstract: To create strains that have high productivity of lactic acid without neutralization, a genome-wide screening for strains showing hyper-resistance to 6% l-lactic acid (pH 2.6) was performed using the gene deletion collection of Saccharomyces cerevisiae. We identified 94 genes whose disruption led to resistance to 6% lactic acid in rich medium. We also found that multiple combinations of Δdse2, Δscw11, Δeaf3, and/or Δsed1 disruption led to enhanced resistance to lactic acid depending upon their combinations. In particular, the quadruple disruptant Δdse2Δscw11Δeaf3Δsed1 grew well in 6% lactic acid with the shortest lag phase. We then introduced an exogenous lactate dehydrogenase gene (LDH) into those single and multiple disruptants to evaluate their productivity of lactic acid. It was found that the quadruple disruptant displaying highest lactic-acid resistance showed a 27% increase of lactic-acid productivity as compared with the LDH-harboring wild-type strain. These observations suggest that disruption of multiple genes whose deletion leads to lactic-acid resistance is an effective way to enhance resistance to lactic acid, leading to high lactic-acid productivity without neutralization.
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Minetaka
authors.initials: M
authors.lastname: Sugiyama
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ishida
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kambe
authors.forename: Shusei
authors.initials: S
authors.lastname: Obata
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Haruo
authors.initials: H
authors.lastname: Takahashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Harashima
mesh_terms: D003470:Culture Media; D017353:Gene Deletion; D005800:Genes, Fungal; D006863:Hydrogen-Ion Concentration; D007770:L-Lactate Dehydrogenase / Q000235:genetics; D019344:Lactic Acid / Q000096:biosynthesis*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism
chemical_list: D003470:Culture Media; D019344:Lactic Acid; D007770:L-Lactate Dehydrogenase