Systematic engineering of microorganisms to improve alcohol tolerance

Microbial production of alcohol is a promising approach for obtaining important chemicals and fuels from renewable carbon resources. One of the key problems associated with the fermentative production of alcohol is alcohol toxicity and/or growth inhibition, resulting in a low alcohol titer in the fermentation broth. Cost‐effective production of alcohol needs the scientific community to engineer microbes for increased alcohol tolerance. Here, based on the understanding of the mechanisms of alcohol toxicity and alcohol stress resistance, we review the recent progress in engineering microbial alcohol tolerance by rational approaches. In addition, random approaches including traditional mutagenesis and selection, evolution engineering, random knockout and overexpression libraries, genome shuffling, replicational/transcriptional/translational engineering were also included into this review.

[1]  H. Biebl,et al.  Production of 1,3-propanediol by Clostridium butyricum DSM 5431 and product tolerant mutants in fedbatch culture: Feeding strategy for glycerol and ammonium , 1996, Biotechnology Letters.

[2]  J. Liao,et al.  An integrated network approach identifies the isobutanol response network of Escherichia coli , 2009, Molecular systems biology.

[3]  B. Kamm,et al.  Production of platform chemicals and synthesis gas from biomass. , 2007, Angewandte Chemie.

[4]  G. Stephanopoulos,et al.  Selection and optimization of microbial hosts for biofuels production. , 2008, Metabolic engineering.

[5]  L. Ingram,et al.  Effects of alcohols on micro-organisms. , 1984, Advances in microbial physiology.

[6]  L. Hou,et al.  Effect of overexpression of transcription factors on the fermentation properties of Saccharomyces cerevisiae industrial strains , 2009, Letters in applied microbiology.

[7]  M. Young,et al.  Butanol tolerance of Clostridium beijerinckii NCIMB 8052 associated with down-regulation of gldA by antisense RNA. , 2000, Journal of molecular microbiology and biotechnology.

[8]  Ramon Gonzalez,et al.  Gene Array‐Based Identification of Changes That Contribute to Ethanol Tolerance in Ethanologenic Escherichia coli: Comparison of KO11 (Parent) to LY01 (Resistant Mutant) , 2003, Biotechnology progress.

[9]  Yoshio Katakura,et al.  Identification of target genes conferring ethanol stress tolerance to Saccharomyces cerevisiae based on DNA microarray data analysis. , 2007, Journal of biotechnology.

[10]  Katsuhide Fujita,et al.  The genome-wide screening of yeast deletion mutants to identify the genes required for tolerance to ethanol and other alcohols. , 2006, FEMS yeast research.

[11]  H. Takagi,et al.  Effect of l-Proline on Sake Brewing and Ethanol Stress in Saccharomyces cerevisiae , 2005, Applied and Environmental Microbiology.

[12]  Mamoru Watanabe,et al.  Overexpression of MSN2 in a sake yeast strain promotes ethanol tolerance and increases ethanol production in sake brewing. , 2009, Journal of bioscience and bioengineering.

[13]  L. Blank,et al.  Selected Pseudomonas putida Strains Able To Grow in the Presence of High Butanol Concentrations , 2009, Applied and Environmental Microbiology.

[14]  Nathan D. Price,et al.  Achievements and perspectives to overcome the poor solvent resistance in acetone and butanol-producing microorganisms , 2010, Applied Microbiology and Biotechnology.

[15]  S. Kashket,et al.  Maintenance of DpH by a butanol-tolerant mutant of Clostridium beijerinckii , 2004 .

[16]  Yanping Zhang,et al.  Engineering Clostridium Strain to Accept Unmethylated DNA , 2010, PloS one.

[17]  D. T. Jones,et al.  Acetone-butanol fermentation revisited. , 1986, Microbiological reviews.

[18]  James A. Williams,et al.  Strain Engineering by Genome Mass Transfer: Efficient Chromosomal Trait Transfer Method Utilizing Donor Genomic DNA and Recipient Recombineering Hosts , 2009, Molecular biotechnology.

[19]  G. Goma,et al.  Butanol tolerance and autobacteriocin production byClostridium acetobutylicum , 1987, Current Microbiology.

[20]  G. Stanley,et al.  Trehalose promotes the survival of Saccharomyces cerevisiae during lethal ethanol stress, but does not influence growth under sublethal ethanol stress. , 2009, FEMS yeast research.

[21]  T. Leathers,et al.  Lactobacillus buchneri strain NRRL B-30929 converts a concentrated mixture of xylose and glucose into ethanol and other products , 2008, Journal of Industrial Microbiology & Biotechnology.

[22]  Xiao-Jun Ji,et al.  Enhanced 2,3-butanediol production by altering the mixed acid fermentation pathway in Klebsiella oxytoca , 2008, Biotechnology Letters.

[23]  G. Stephanopoulos,et al.  Engineering Yeast Transcription Machinery for Improved Ethanol Tolerance and Production , 2006, Science.

[24]  K. Prather,et al.  Engineering alternative butanol production platforms in heterologous bacteria. , 2009, Metabolic engineering.

[25]  Heui-Dong Park,et al.  Antisense-Mediated Inhibition of Acid Trehalase (ATH1) Gene Expression Promotes Ethanol Fermentation and Tolerance in Saccharomyces cerevisiae , 2005, Biotechnology Letters.

[26]  L. Nielsen,et al.  Fermentative butanol production by clostridia , 2008, Biotechnology and bioengineering.

[27]  Alyssa M. Redding,et al.  Metabolic engineering of Saccharomyces cerevisiae for the production of n-butanol , 2008, Microbial cell factories.

[28]  K. Horikoshi,et al.  A Pseudomonas thrives in high concentrations of toluene , 1989, Nature.

[29]  K. Shanmugam,et al.  Lack of Protective Osmolytes Limits Final Cell Density and Volumetric Productivity of Ethanologenic Escherichia coli KO11 during Xylose Fermentation , 2004, Applied and Environmental Microbiology.

[30]  C. Tomas,et al.  Overexpression of groESL in Clostridium acetobutylicum Results in Increased Solvent Production and Tolerance, Prolonged Metabolism, and Changes in the Cell's Transcriptional Program , 2003, Applied and Environmental Microbiology.

[31]  J. D. de Bont,et al.  Adaptation of Pseudomonas putida S12 to high concentrations of styrene and other organic solvents , 1993, Applied and environmental microbiology.

[32]  A. Schmid,et al.  Biotransformation in Double-Phase Systems: Physiological Responses of Pseudomonas putida DOT-T1E to a Double Phase Made of Aliphatic Alcohols and Biosynthesis of Substituted Catechols , 2004, Applied and Environmental Microbiology.

[33]  E. Papoutsakis.  Engineering solventogenic clostridia. , 2008, Current opinion in biotechnology.

[34]  Yajun Yan,et al.  Engineering metabolic systems for production of advanced fuels , 2009, Journal of Industrial Microbiology & Biotechnology.

[35]  Yuki Takaoka,et al.  Ethanol-tolerant Saccharomyces cerevisiae strains isolated under selective conditions by over-expression of a proofreading-deficient DNA polymerase delta. , 2009, Journal of bioscience and bioengineering.

[36]  Farren J. Isaacs,et al.  Programming cells by multiplex genome engineering and accelerated evolution , 2009, Nature.

[37]  Nasib Qureshi,et al.  Butanol production from wheat straw hydrolysate using Clostridium beijerinckii , 2007, Bioprocess and biosystems engineering.

[38]  James J. Collins,et al.  Next-Generation Synthetic Gene Networks , 2009, Nature Biotechnology.

[39]  Nasib Qureshi,et al.  Butanol fermentation research: upstream and downstream manipulations. , 2004, Chemical record.

[40]  E. Papoutsakis,et al.  Characterization of recombinant strains of the Clostridium acetobutylicum butyrate kinase inactivation mutant: need for new phenomenological models for solventogenesis and butanol inhibition? , 2000, Biotechnology and bioengineering.

[41]  E. Papoutsakis,et al.  Dynamics of Genomic-Library Enrichment and Identification of Solvent Tolerance Genes for Clostridium acetobutylicum , 2007, Applied and Environmental Microbiology.

[42]  C. Snowdon,et al.  ETP1/YHL010c is a novel gene needed for the adaptation of Saccharomyces cerevisiae to ethanol. , 2009, FEMS yeast research.

[43]  H. Blaschek,et al.  Transcriptional Analysis of Clostridium beijerinckii NCIMB 8052 and the Hyper-Butanol-Producing Mutant BA101 during the Shift from Acidogenesis to Solventogenesis , 2008, Applied and Environmental Microbiology.

[44]  H. Heipieper,et al.  Ethanol tolerance and membrane fatty acid adaptation in adh multiple and null mutants of Kluyveromyces lactis. , 2000, Research in microbiology.

[45]  David T. Jones,et al.  Autolytic Activity and Butanol Tolerance of Clostridium acetobutylicum , 1982, Applied and environmental microbiology.

[46]  K. Ganesan,et al.  Critical role of RPI1 in the stress tolerance of yeast during ethanolic fermentation. , 2009, FEMS yeast research.

[47]  D. Klionsky,et al.  Disruption of the yeast ATH1 gene confers better survival after dehydration, freezing, and ethanol shock: potential commercial applications , 1996, Applied and environmental microbiology.

[48]  T. Abee,et al.  Membrane Fluidity Adjustments in Ethanol-Stressed Oenococcus oeni Cells , 2003, Applied and Environmental Microbiology.

[49]  Dong-jian Shi,et al.  Genome shuffling to improve thermotolerance, ethanol tolerance and ethanol productivity of Saccharomyces cerevisiae , 2008, Journal of Industrial Microbiology & Biotechnology.

[50]  P. Rogers,et al.  Generation and characterisation of stable ethanol-tolerant mutants of Saccharomyces cerevisiae , 2010, Journal of Industrial Microbiology & Biotechnology.

[51]  Maintenance of DeltapH by a butanol-tolerant mutant of Clostridium beijerinckii. , 2005, Microbiology.

[52]  T. Ezeji,et al.  Bioproduction of butanol from biomass: from genes to bioreactors. , 2007, Current opinion in biotechnology.

[53]  Zugen Chen,et al.  Proteome reference map and comparative proteomic analysis between a wild type Clostridium acetobutylicum DSM 1731 and its mutant with enhanced butanol tolerance and butanol yield. , 2010, Journal of proteome research.

[54]  G. Stewart,et al.  Ethanol tolerance of yeast , 1987 .

[55]  J. Zeikus,et al.  Ethanol Production by Thermophilic Bacteria: Physiological Comparison of Solvent Effects on Parent and Alcohol-Tolerant Strains of Clostridium thermohydrosulfuricum , 1984, Applied and environmental microbiology.

[56]  S. Jennewein,et al.  Genome Shuffling in Clostridium diolis DSM 15410 for Improved 1,3-Propanediol Production , 2009, Applied and Environmental Microbiology.

[57]  L. Ingram,et al.  Isolation and characterization of ethanol-tolerant mutants of Escherichia coli KO11 for fuel ethanol production , 1998, Journal of Industrial Microbiology and Biotechnology.

[58]  N. Qureshi,et al.  How microbes tolerate ethanol and butanol. , 2009, New biotechnology.

[59]  Dae-Hyuk Kim,et al.  Improved ethanol tolerance in Escherichia coli by changing the cellular fatty acids composition through genetic manipulation , 2009, Biotechnology Letters.

[60]  C. Abbas,et al.  Heterologous expression of Saccharomyces cerevisiae MPR1 gene confers tolerance to ethanol and l-azetidine-2-carboxylic acid in Hansenula polymorpha , 2010, Journal of Industrial Microbiology & Biotechnology.

[61]  M. Roberts,et al.  31P NMR studies of Clostridium thermocellum. Mechanism of end product inhibition by ethanol. , 1985, The Journal of biological chemistry.

[62]  Junmei Ding,et al.  Tolerance and stress response to ethanol in the yeast Saccharomyces cerevisiae , 2009, Applied Microbiology and Biotechnology.

[63]  E. Nevoigt,et al.  Progress in Metabolic Engineering of Saccharomyces cerevisiae , 2008, Microbiology and Molecular Biology Reviews.

[64]  Yan Zhu,et al.  The Importance of Engineering Physiological Functionality into Microbes Opinion , 2022 .

[65]  K. Kitamoto,et al.  Elevated expression of genes under the control of stress response element (STRE) and Msn2p in an ethanol-tolerance sake yeast Kyokai no. 11. , 2007, Journal of bioscience and bioengineering.

[66]  Gregory Stephanopoulos,et al.  Combinatorial engineering of microbes for optimizing cellular phenotype. , 2008, Current opinion in chemical biology.

[67]  E. Papoutsakis,et al.  Metabolite stress and tolerance in the production of biofuels and chemicals: Gene‐expression‐based systems analysis of butanol, butyrate, and acetate stresses in the anaerobe Clostridium acetobutylicum , 2010, Biotechnology and bioengineering.

[68]  L. Ingram,et al.  Enhanced Trehalose Production Improves Growth of Escherichia coli under Osmotic Stress , 2005, Applied and Environmental Microbiology.

[69]  T. Conway,et al.  Ethanol tolerance and carbohydrate metabolism in lactobacilli , 1992, Journal of Industrial Microbiology.

[70]  A. Herrero,et al.  Development of ethanol tolerance in Clostridium thermocellum: effect of growth temperature , 1980, Applied and environmental microbiology.

[71]  Min Zhang,et al.  Butanol Tolerance in a Selection of Microorganisms , 2009, Applied biochemistry and biotechnology.

[72]  Jay D Keasling,et al.  Importance of systems biology in engineering microbes for biofuel production. , 2008, Current opinion in biotechnology.

[73]  L. Hindorff,et al.  Expression of a Cloned Cyclopropane Fatty Acid Synthase Gene Reduces Solvent Formation in Clostridium acetobutylicum ATCC 824 , 2003, Applied and Environmental Microbiology.

[74]  C. Tomas,et al.  Transcriptional Analysis of Butanol Stress and Tolerance in Clostridium acetobutylicum , 2004, Journal of bacteriology.

[75]  G. Stephanopoulos,et al.  Mutagenesis of the Bacterial RNA Polymerase Alpha Subunit for Improvement of Complex Phenotypes , 2009, Applied and Environmental Microbiology.

[76]  G. Stephanopoulos,et al.  Global transcription machinery engineering: a new approach for improving cellular phenotype. , 2007, Metabolic engineering.

[77]  E. Papoutsakis,et al.  Transcriptional Analysis of spo0A Overexpression in Clostridium acetobutylicum and Its Effect on the Cell's Response to Butanol Stress , 2004, Journal of bacteriology.

[78]  Jay D. Keasling,et al.  Functional Genomic Study of Exogenous n-Butanol Stress in Escherichia coli , 2010, Applied and Environmental Microbiology.

[79]  J. Liao,et al.  Non-fermentative pathways for synthesis of branched-chain higher alcohols as biofuels , 2008, Nature.

[80]  K. Ito,et al.  Identification of genes required for growth under ethanol stress using transposon mutagenesis in Saccharomyces cerevisiae , 2001, Molecular Genetics and Genomics.