title: Improvement of glucose uptake rate and production of target chemicals by overexpressing hexose transporters and transcriptional activator Gcr1 in Saccharomyces cerevisiae.
abstract: Metabolic engineering to increase the glucose uptake rate might be beneficial to improve microbial production of various fuels and chemicals. In this study, we enhanced the glucose uptake rate in Saccharomyces cerevisiae by overexpressing hexose transporters (HXTs). Among the 5 tested HXTs (Hxt1, Hxt2, Hxt3, Hxt4, and Hxt7), overexpression of high-affinity transporter Hxt7 was the most effective in increasing the glucose uptake rate, followed by moderate-affinity transporters Hxt2 and Hxt4. Deletion of STD1 and MTH1, encoding corepressors of HXT genes, exerted differential effects on the glucose uptake rate, depending on the culture conditions. In addition, improved cell growth and glucose uptake rates could be achieved by overexpression of GCR1, which led to increased transcription levels of HXT1 and ribosomal protein genes. All genetic modifications enhancing the glucose uptake rate also increased the ethanol production rate in wild-type S. cerevisiae. Furthermore, the growth-promoting effect of GCR1 overexpression was successfully applied to lactic acid production in an engineered lactic acid-producing strain, resulting in a significant improvement of productivity and titers of lactic acid production under acidic fermentation conditions.
authors.affiliation: School of Chemical and Biological Engineering, Seoul National University, Seoul, Republic of Korea.
authors.forename: Daehee
authors.initials: D
authors.lastname: Kim
authors.affiliation: School of Chemical and Biological Engineering, Seoul National University, Seoul, Republic of Korea.
authors.forename: Ji-Yoon
authors.initials: JY
authors.lastname: Song
authors.affiliation: School of Chemical and Biological Engineering, Seoul National University, Seoul, Republic of Korea hahnjs@snu.ac.kr.
authors.forename: Ji-Sook
authors.initials: JS
authors.lastname: Hahn
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D001693:Biological Transport, Active / Q000235:genetics*; D050260:Carbohydrate Metabolism / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D000431:Ethanol / Q000378:metabolism; D005285:Fermentation / Q000235:genetics / Q000502:physiology; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D005947:Glucose / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D019344:Lactic Acid / Q000096:biosynthesis*; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C076227:GCR1 protein, S cerevisiae; D047908:Intracellular Signaling Peptides and Proteins; C118806:MTH1 protein, S cerevisiae; D009004:Monosaccharide Transport Proteins; C081335:STD1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D019344:Lactic Acid; D000431:Ethanol; D005947:Glucose