title: Systems-level understanding of ethanol-induced stresses and adaptation in E. coli.
abstract: Understanding ethanol-induced stresses and responses in biofuel-producing bacteria at systems level has significant implications in engineering more efficient biofuel producers. We present a computational study of transcriptomic and genomic data of both ethanol-stressed and ethanol-adapted E. coli cells with computationally predicated ethanol-binding proteins and experimentally identified ethanol tolerance genes. Our analysis suggests: (1) ethanol damages cell wall and membrane integrity, causing increased stresses, particularly reactive oxygen species, which damages DNA and reduces the O2level; (2) decreased cross-membrane proton gradient from membrane damage, coupled with hypoxia, leads to reduced ATP production by aerobic respiration, driving cells to rely more on fatty acid oxidation, anaerobic respiration and fermentation for ATP production; (3) the reduced ATP generation results in substantially decreased synthesis of macromolecules; (4) ethanol can directly bind 213 proteins including transcription factors, altering their functions; (5) all these changes together induce multiple stress responses, reduced biosynthesis, cell viability and growth; and (6) ethanol-adapted E. coli cells restore the majority of these reduced activities through selection of specific genomic mutations and alteration of stress responses, ultimately restoring normal ATP production, macromolecule biosynthesis, and growth. These new insights into the energy and mass balance will inform design of more ethanol-tolerant strains.
authors.affiliation: Computational Systems Biology Laboratory, Department of Biochemistry and Molecular Biology, and Institute of Bioinformatics, the University of Georgia, Athens, GA 30602, USA.|BioEnergy Science Center, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA.
authors.forename: Huansheng
authors.initials: H
authors.lastname: Cao
authors.affiliation: Computational Systems Biology Laboratory, Department of Biochemistry and Molecular Biology, and Institute of Bioinformatics, the University of Georgia, Athens, GA 30602, USA.|College of Computer Science and Technology, Jilin University, Changchun, 130012, China.
authors.forename: Du
authors.initials: D
authors.lastname: Wei
authors.affiliation: Institute for Glycomics and School of Information and Communication Technology, Griffith University, Parklands Dr., Southport, QLD 4222, Australia.
authors.forename: Yuedong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Computational Systems Biology Laboratory, Department of Biochemistry and Molecular Biology, and Institute of Bioinformatics, the University of Georgia, Athens, GA 30602, USA.|College of Computer Science and Technology, Jilin University, Changchun, 130012, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Shang
authors.affiliation: Computational Systems Biology Laboratory, Department of Biochemistry and Molecular Biology, and Institute of Bioinformatics, the University of Georgia, Athens, GA 30602, USA.|College of Computer Science and Technology, Jilin University, Changchun, 130012, China.
authors.forename: Gaoyang
authors.initials: G
authors.lastname: Li
authors.affiliation: Institute for Glycomics and School of Information and Communication Technology, Griffith University, Parklands Dr., Southport, QLD 4222, Australia.
authors.forename: Yaoqi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Agronomy, Horticulture and Plant Science, South Dakota State University, Brookings, SD 57007, USA.|BioSNTR, Brookings, SD, 57007, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Computational Systems Biology Laboratory, Department of Biochemistry and Molecular Biology, and Institute of Bioinformatics, the University of Georgia, Athens, GA 30602, USA.|BioEnergy Science Center, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA.|College of Computer Science and Technology, Jilin University, Changchun, 130012, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000220:Adaptation, Biological / Q000187:drug effects* / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D013312:Stress, Physiological / Q000187:drug effects* / Q000235:genetics
chemical_list: D000431:Ethanol