title: The zinc cluster transcriptional regulator Asg1 transcriptionally coordinates oleate utilization and lipid accumulation in Saccharomyces cerevisiae.
abstract: In this study, we characterize a new function for activator of stress response genes (Asg1) in fatty acid utilization. Asg1 is required for full activation of genes in several pathways, including β-oxidation (POX1, FOX2, and POT1), gluconeogenesis (PCK1), glyoxylate cycle (ICL1), triacylglycerol breakdown (TGL3), and peroxisomal transport (PXA1). In addition, the transcriptional activator Asg1 is found to be enriched on promoters of genes in β-oxidation and gluconeogenesis pathways, suggesting that Asg1 is directly involved in the control of fatty acid utilizing genes. In agreement, impaired growth on non-fermentable carbons such as fatty acids and oils and increased sensitivity to some oxidative agents are found for the Δasg1 strain. The lipid class profile of the Δasg1 cells grown in oleate displays approximately 3-fold increase in free fatty acid (FFA) content in comparison to glucose-grown cells, which correlates with decreased expression of β-oxidation genes. The ∆asg1 strain grown in glucose also exhibits higher accumulation of triacylglycerols (TAGs) during log phase, reaching levels typically observed in stationary phase cells. Altered TAG accumulation is partly due to the inability of the Δasg1 cells to efficiently break down TAGs, which is consistent with lowered expression of TGL3 gene, encoding triglycerol lipase. Overall, these results highlight a new role of the transcriptional regulator Asg1 in coordinating expression of genes involved in fatty acid utilization and its role in regulating cellular lipid accumulation, thereby providing an attractive approach to increase FFAs and TAGs content for the production of lipid-derived biofuels and chemicals in Saccharomyces cerevisiae.
authors.affiliation: Division of Biochemical Technology, School of Bioresources and Technology, King Mongkut's University of Technology Thonburi, 49 Tianthalay Road, Tha Kham, Bangkhuntian, Bangkok, 10150, Thailand.
authors.forename: Siripat
authors.initials: S
authors.lastname: Jansuriyakul
authors.affiliation: Division of Biochemical Technology, School of Bioresources and Technology, King Mongkut's University of Technology Thonburi, 49 Tianthalay Road, Tha Kham, Bangkhuntian, Bangkok, 10150, Thailand.
authors.forename: Pichayada
authors.initials: P
authors.lastname: Somboon
authors.affiliation: Division of Biochemical Technology, School of Bioresources and Technology, King Mongkut's University of Technology Thonburi, 49 Tianthalay Road, Tha Kham, Bangkhuntian, Bangkok, 10150, Thailand.
authors.forename: Napachai
authors.initials: N
authors.lastname: Rodboon
authors.affiliation: NAS of Ukraine, Institute of Cell Biology, Drahomanov Street, 14/16, Lviv, 79005, Ukraine.
authors.forename: Olena
authors.initials: O
authors.lastname: Kurylenko
authors.affiliation: NAS of Ukraine, Institute of Cell Biology, Drahomanov Street, 14/16, Lviv, 79005, Ukraine.|Department of Bioetchnology and Microbiology, University of Rzeszow, Zelwerowicza Street, 4, 35-601, Rzeszow, Poland.
authors.forename: Andriy
authors.initials: A
authors.lastname: Sibirny
authors.affiliation: Division of Biochemical Technology, School of Bioresources and Technology, King Mongkut's University of Technology Thonburi, 49 Tianthalay Road, Tha Kham, Bangkhuntian, Bangkok, 10150, Thailand. nitnipa.soo@kmutt.ac.th.
authors.forename: Nitnipa
authors.initials: N
authors.lastname: Soontorngun
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D042962:Acyl-CoA Oxidase / Q000235:genetics / Q000378:metabolism; D056804:Biofuels / Q000382:microbiology; D003470:Culture Media / Q000737:chemistry; D004746:Enoyl-CoA Hydratase / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005943:Gluconeogenesis; D007218:Industrial Microbiology; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D005810:Multigene Family; D019301:Oleic Acid / Q000378:metabolism*; D018384:Oxidative Stress; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism; D016335:Zinc Fingers
chemical_list: D018528:ATP-Binding Cassette Transporters; C000614857:Asg1 protein, S cerevisiae; D056804:Biofuels; D003470:Culture Media; D005227:Fatty Acids; C098338:PXA1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014280:Triglycerides; D019301:Oleic Acid; D015094:3-Hydroxyacyl CoA Dehydrogenases; D042962:Acyl-CoA Oxidase; C467991:POX1 protein, S cerevisiae; D008049:Lipase; C476342:TGL3 protein, S cerevisiae; D004746:Enoyl-CoA Hydratase; C073759:FOX2 protein, S cerevisiae
keywords: Fatty acid metabolism; Gene regulation; Oxidative stress; S. cerevisiae; Triacylglycerol; β-oxidation