title: Intracellular metabolite profiling of Saccharomyces cerevisiae evolved under furfural.
abstract: Furfural, one of the most common inhibitors in pre-treatment hydrolysates, reduces the cell growth and ethanol production of yeast. Evolutionary engineering has been used as a selection scheme to obtain yeast strains that exhibit furfural tolerance. However, the response of Saccharomyces cerevisiae to furfural at the metabolite level during evolution remains unknown. In this study, evolutionary engineering and metabolomic analyses were applied to determine the effects of furfural on yeasts and their metabolic response to continuous exposure to furfural. After 50 serial transfers of cultures in the presence of furfural, the evolved strains acquired the ability to stably manage its physiological status under the furfural stress. A total of 98 metabolites were identified, and their abundance profiles implied that yeast metabolism was globally regulated. Under the furfural stress, stress-protective molecules and cofactor-related mechanisms were mainly induced in the parental strain. However, during evolution under the furfural stress, S. cerevisiae underwent global metabolic allocations to quickly overcome the stress, particularly by maintaining higher levels of metabolites related to energy generation, cofactor regeneration and recovery from cellular damage. Mapping the mechanisms of furfural tolerance conferred by evolutionary engineering in the present study will be led to rational design of metabolically engineered yeasts.
authors.affiliation: School of Food Science and Biotechnology, Kyungpook National University, Daegu, 41566, South Korea.
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Jung
authors.affiliation: Department of Biotechnology, Graduate School, Korea University, Seoul, 02841, South Korea.
authors.forename: Sooah
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Graduate School, Korea University, Seoul, 02841, South Korea.
authors.forename: Jungwoo
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, 08826, South Korea.
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Seo
authors.affiliation: Department of Biotechnology, Graduate School, Korea University, Seoul, 02841, South Korea.
authors.forename: Kyoung Heon
authors.initials: KH
authors.lastname: Kim
mesh_terms: D000220:Adaptation, Biological; D000935:Antifungal Agents / Q000378:metabolism*; D004361:Drug Tolerance; D005662:Furaldehyde / Q000378:metabolism*; D055442:Metabolome; D055432:Metabolomics; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000187:drug effects / Q000254:growth & development*; D012692:Serial Passage
chemical_list: D000935:Antifungal Agents; D005662:Furaldehyde