title: Inverse metabolic engineering based on transient acclimation of yeast improves acid-containing xylose fermentation and tolerance to formic and acetic acids.
abstract: Improving the production of ethanol from xylose is an important goal in metabolic engineering of Saccharomyces cerevisiae. Furthermore, S. cerevisiae must produce ethanol in the presence of weak acids (formate and acetate) generated during pre-treatment of lignocellulosic biomass. In this study, weak acid-containing xylose fermentation was significantly improved using cells that were acclimated to the weak acids during pre-cultivation. Transcriptome analyses showed that levels of transcripts for transcriptional/translational machinery-related genes (RTC3 and ANB1) were enhanced by formate and acetate acclimation. Recombinant yeast strains overexpressing RTC3 and ANB1 demonstrated improved ethanol production from xylose in the presence of the weak acids, along with improved tolerance to the acids. Novel metabolic engineering strategy based on the combination of short-term acclimation and system-wide analysis was developed, which can develop stress-tolerant strains in a short period of time, although conventional evolutionary engineering approach has required long periods of time to isolate inhibitor-adapted strains.
authors.affiliation: Organization of Advanced Science and Technology, Kobe University, 1-1 Rokkodai, Nada, Kobe, 657-8501, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Hasunuma
authors.affiliation: Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe, 657-8501, Japan.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe, 657-8501, Japan. akondo@kobe-u.ac.jp.|Biomass Engineering Program, RIKEN, 1-7-22 Suehiro, Tsurumi, Yokohama, Kanagawa, 230-0045, Japan. akondo@kobe-u.ac.jp.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kondo
mesh_terms: D000064:Acclimatization / Q000235:genetics / Q000502:physiology*; D019342:Acetic Acid / Q000378:metabolism; D018533:Biomass; D000431:Ethanol / Q000378:metabolism; D005285:Fermentation; D005561:Formates / Q000378:metabolism; D020869:Gene Expression Profiling; D006868:Hydrolysis; D060847:Metabolic Engineering; D010448:Peptide Initiation Factors / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D014994:Xylose / Q000378:metabolism*; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D019342:Acetic Acid; D000431:Ethanol; D005561:Formates; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D014994:Xylose; D000097574:Eukaryotic Translation Initiation Factor 5A; C577221:RTC3 protein, S cerevisiae; C030544:formic acid
keywords: Acclimation; Fermentation inhibitor; Inhibitor tolerance; Saccharomyces cerevisiae; Xylose fermentation