title: Investigate the Metabolic Reprogramming of Saccharomyces cerevisiae for Enhanced Resistance to Mixed Fermentation Inhibitors via 13C Metabolic Flux Analysis.
abstract: The fermentation inhibitors from the pretreatment of lignocellulosic materials, e.g., acetic acid and furfural, are notorious due to their negative effects on the cell growth and chemical production. However, the metabolic reprogramming of the cells under these stress conditions, especially metabolic response for resistance to mixed inhibitors, has not been systematically investigated and remains mysterious. Therefore, in this study, 13C metabolic flux analysis (13C-MFA), a powerful tool to elucidate the intracellular carbon flux distributions, has been applied to two Saccharomyces cerevisiae strains with different tolerances to the inhibitors under acetic acid, furfural, and mixed (i.e., acetic acid and furfural) stress conditions to unravel the key metabolic responses. By analyzing the intracellular carbon fluxes as well as the energy and cofactor utilization under different conditions, we uncovered varied metabolic responses to different inhibitors. Under acetate stress, ATP and NADH production was slightly impaired, while NADPH tended towards overproduction. Under furfural stress, ATP and cofactors (including both NADH and NADPH) tended to be overproduced. However, under dual-stress condition, production of ATP and cofactors was severely impaired due to synergistic stress caused by the simultaneous addition of two fermentation inhibitors. Such phenomenon indicated the pivotal role of the energy and cofactor utilization in resisting the mixed inhibitors of acetic acid and furfural. Based on the discoveries, valuable insights are provided to improve the tolerance of S. cerevisiae strain and further enhance lignocellulosic fermentation.
authors.affiliation: Department of Biological Systems Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, United States of America.
authors.forename: Weihua
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Civil and Environmental Engineering and Earth Sciences, University of Notre Dame, Notre Dame, IN 46556, United States of America.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Civil and Environmental Engineering and Earth Sciences, University of Notre Dame, Notre Dame, IN 46556, United States of America.
authors.forename: Na
authors.initials: N
authors.lastname: Wei
authors.affiliation: Department of Biological Systems Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, United States of America.
authors.forename: Xueyang
authors.initials: X
authors.lastname: Feng
mesh_terms: D019342:Acetic Acid / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D056804:Biofuels / Q000382:microbiology; D002247:Carbon Isotopes / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D005285:Fermentation / Q000187:drug effects* / Q000235:genetics; D005662:Furaldehyde / Q000494:pharmacology*; D007553:Isotope Labeling; D008031:Lignin / Q000378:metabolism; D064688:Metabolic Flux Analysis / Q000379:methods*; D009243:NAD / Q000096:biosynthesis; D009249:NADP / Q000096:biosynthesis; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D013312:Stress, Physiological / Q000187:drug effects
chemical_list: D056804:Biofuels; D002247:Carbon Isotopes; D009243:NAD; C036909:lignocellulose; D009249:NADP; D000255:Adenosine Triphosphate; D008031:Lignin; D005662:Furaldehyde; D019342:Acetic Acid