Enhancing the performance of brewing yeasts.

Beer production is one of the oldest known traditional biotechnological processes, but is nowadays facing increasing demands not only for enhanced product quality, but also for improved production economics. Targeted genetic modification of a yeast strain is one way to increase beer quality and to improve the economics of beer production. In this review we will present current knowledge on traditional approaches for improving brewing strains and for rational metabolic engineering. These research efforts will, in the near future, lead to the development of a wider range of industrial strains that should increase the diversity of commercial beers.

[1]  C. Bamforth,et al.  DIMETHYL SULPHIDE—A REVIEW , 1982 .

[2]  G. Shaffer,et al.  When Cooperation Fails: The International Law and Politics of Genetically Modified Foods , 2009 .

[3]  N. D. Da Silva,et al.  Development and characterization of a vector set with regulated promoters for systematic metabolic engineering in Saccharomyces cerevisiae , 2012, Yeast.

[4]  H. Moriya,et al.  A genome-wide activity assessment of terminator regions in Saccharomyces cerevisiae provides a ″terminatome″ toolbox. , 2013, ACS synthetic biology.

[5]  E. Nevoigt,et al.  Genetic improvement of brewer’s yeast: current state, perspectives and limits , 2010, Applied Microbiology and Biotechnology.

[6]  N. Jausovec,et al.  The influence of intelligence and emotions on the acceptability of genetically modified organisms , 2012 .

[7]  N. Urano,et al.  Conversion of a non-flocculent brewer's yeast to flocculent ones by electrofusion , 1993 .

[8]  Huimin Zhao,et al.  Recent advances in DNA assembly technologies. , 2014, FEMS yeast research.

[9]  J. Teixeira,et al.  A review of flavour formation in continuous beer fermentations , 2008 .

[10]  L. Kruglyak,et al.  Finding the sources of missing heritability in a yeast cross , 2012, Nature.

[11]  D. Xiao,et al.  Construction of recombinant industrial brewer’s yeast with lower diacetyl production and proteinase A activity , 2012, European Food Research and Technology.

[12]  E. Storgårds,et al.  Comparative physiology and fermentation performance of Saaz and Frohberg lager yeast strains and the parental species Saccharomyces eubayanus , 2013, Yeast.

[13]  P Manivasakam,et al.  Micro-homology mediated PCR targeting in Saccharomyces cerevisiae. , 1995, Nucleic acids research.

[14]  Guangyi Zhang,et al.  Mutagenizing brewing yeast strain for improving fermentation property of beer. , 2008, Journal of bioscience and bioengineering.

[15]  Sanghoon Ko,et al.  Very high gravity (VHG) ethanolic brewing and fermentation: a research update , 2011, Journal of Industrial Microbiology & Biotechnology.

[16]  Freddy R. Delvaux,et al.  Isolation and Characterization of Brewer's Yeast Variants with Improved Fermentation Performance under High-Gravity Conditions , 2006, Applied and Environmental Microbiology.

[17]  M. Goddard,et al.  Saccharomyces eubayanus and Saccharomyces arboricola reside in North Island native New Zealand forests. , 2016, Environmental microbiology.

[18]  V. Vidgren,et al.  Novel brewing yeast hybrids: creation and application , 2016, Applied Microbiology and Biotechnology.

[19]  Leonid Kruglyak,et al.  Dissection of genetically complex traits with extremely large pools of yeast segregants , 2010, Nature.

[20]  A. Kondo,et al.  Cell surface engineering of industrial microorganisms for biorefining applications. , 2015, Biotechnology advances.

[21]  M. Mokrejs,et al.  Sequencing the genome of bottom brewer´s yeast , 2013 .

[22]  K. Krogerus,et al.  125th Anniversary Review: Diacetyl and its control during brewery fermentation , 2013 .

[23]  J. François,et al.  A metabolic and genomic study of engineered Saccharomyces cerevisiae strains for high glycerol production. , 2007, Metabolic engineering.

[24]  H. Boucherie,et al.  Two‐dimensional gel analysis of the proteome of lager brewing yeasts , 2000, Yeast.

[25]  G. P. Casey,et al.  Developments in sporulation and breeding of brewer's yeast , 1989 .

[26]  D. Xiao,et al.  Reduced production of diacetyl by overexpressing BDH2 gene and ILV5 gene in yeast of the lager brewers with one ILV2 allelic gene deleted , 2017, Journal of Industrial Microbiology & Biotechnology.

[27]  S. Dequin,et al.  The potential of genetic engineering for improving brewing, wine-making and baking yeasts , 2001, Applied Microbiology and Biotechnology.

[28]  G. Church,et al.  Cas9 as a versatile tool for engineering biology , 2013, Nature Methods.

[29]  Mark Johnston,et al.  Microbe domestication and the identification of the wild genetic stock of lager-brewing yeast , 2011, Proceedings of the National Academy of Sciences.

[30]  M. Takashio,et al.  Breeding of brewer's yeast by hybridization between a top-fermenting yeast Saccharomyces cerevisiae and a cryophilic yeast Saccharomyces bayanus. , 2002, Journal of bioscience and bioengineering.

[31]  P. Dostálek,et al.  Development of engineered yeast for biosorption of beer haze-active polyphenols , 2016, Applied Microbiology and Biotechnology.

[32]  Keun Kim,et al.  The construction of a stable starch-fermenting yeast strain using genetic engineering and rare-mating , 1996, Applied biochemistry and biotechnology.

[33]  Huimin Zhao,et al.  Customized optimization of metabolic pathways by combinatorial transcriptional engineering. , 2013, Methods in molecular biology.

[34]  K. K. Thomsen,et al.  Construction of a yeast vector directing the synthesis and release of barley (1→3, 1→4)-β-glucanase , 1986 .

[35]  K. Ülgen,et al.  Bioconversion of starch into ethanol by a recombinant Saccharomyces cerevisiae strain YPG-AB , 2002 .

[36]  D. Xiao,et al.  Increased esters and decreased higher alcohols production by engineered brewer’s yeast strains , 2013, European Food Research and Technology.

[37]  M. Penttilä,et al.  Construction of brewer's yeasts secreting fungal endo-ß-glucanase , 1987, Current Genetics.

[38]  Yong-Su Jin,et al.  Optimal Growth and Ethanol Production from Xylose by Recombinant Saccharomyces cerevisiae Require Moderate d-Xylulokinase Activity , 2003, Applied and Environmental Microbiology.

[39]  W. Hsu,et al.  Construction of an amylolytic yeast by multiple integration of the Aspergillus awamori glucoamylase gene into a Saccharomyces cerevisiae chromosome , 1998 .

[40]  G. Stephanopoulos,et al.  Tuning genetic control through promoter engineering. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[41]  A. Querol,et al.  Analysis of the genetic variability in the species of the Saccharomyces sensu stricto complex , 2003, Yeast.

[42]  Gavin Sherlock,et al.  Saccharomyces pastorianus lager yeast Reconstruction of the genome origins and evolution of the hybrid Material Supplemental , 2008 .

[43]  D. Xiao,et al.  Intergeneric yeast fusants with efficient ethanol production from cheese whey powder solution: Construction of a Kluyveromyces marxianus and Saccharomyces cerevisiae AY‐5 hybrid , 2012 .

[44]  P. Dostálek,et al.  Biologically Active Compounds from Hops and Prospects for Their Use. , 2016, Comprehensive reviews in food science and food safety.

[45]  A. Mizuno,et al.  Characterization of low-acetic-acid-producing yeast isolated from 2-deoxyglucose-resistant mutants and its application to high-gravity brewing. , 2006, Journal of bioscience and bioengineering.

[46]  H. Maki,et al.  Spontaneous loss of heterozygosity in diploid Saccharomyces cerevisiae cells. , 2000, Genetics.

[47]  J. Hansen.  Inactivation of MXR1 Abolishes Formation of Dimethyl Sulfide from Dimethyl Sulfoxide inSaccharomyces cerevisiae , 1999, Applied and Environmental Microbiology.

[48]  Akihiko Kondo,et al.  Cell-surface display of enzymes by the yeast Saccharomyces cerevisiae for synthetic biology. , 2014, FEMS yeast research.

[49]  A. Jimenez,et al.  Construction of an efficient amylolytic industrial yeast strain containing DNA exclusively derived from yeast. , 2001, FEMS microbiology letters.

[50]  H. Azadi,et al.  Genetically Modified and Organic Crops in Developing Countries: A Review of Options for Food Security , 2009, Biotechnology advances.

[51]  Merja Penttilä,et al.  Yeast oligo-mediated genome engineering (YOGE). , 2013, ACS synthetic biology.

[52]  Jan Steensels,et al.  Improving industrial yeast strains: exploiting natural and artificial diversity , 2014, FEMS microbiology reviews.

[53]  D. Saison,et al.  Decrease of 4-vinylguaiacol during beer aging and formation of apocynol and vanillin in beer. , 2008, Journal of agricultural and food chemistry.

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

[55]  L. Parts.  Genome‐wide mapping of cellular traits using yeast , 2014, Yeast.

[56]  Hal S Alper,et al.  The synthetic biology toolbox for tuning gene expression in yeast. , 2014, FEMS yeast research.

[57]  A. Querol,et al.  The complex and dynamic genomes of industrial yeasts. , 2009, FEMS microbiology letters.

[58]  I. Pretorius,et al.  Starch fermentation by recombinant saccharomyces cerevisiae strains expressing the α‐amylase and glucoamylase genes from lipomyces kononenkoae and saccharomycopsis fibuligera , 2003, Biotechnology and bioengineering.

[59]  Verena Siewers,et al.  Characterization of chromosomal integration sites for heterologous gene expression in Saccharomyces cerevisiae , 2009, Yeast.

[60]  C. Fadda,et al.  Aging of craft durum wheat beer fermented with sourdough yeasts , 2016 .

[61]  Y. Kaneko,et al.  Pure and Mixed Genetic Lines of Saccharomyces bayanus and Saccharomyces pastorianus and Their Contribution to the Lager Brewing Strain Genome , 2006, Applied and Environmental Microbiology.

[62]  Ralph A. Cacho,et al.  Discovery of Unclustered Fungal Indole Diterpene Biosynthetic Pathways through Combinatorial Pathway Reassembly in Engineered Yeast. , 2015, Journal of the American Chemical Society.

[63]  Jef D Boeke,et al.  RADOM, an efficient in vivo method for assembling designed DNA fragments up to 10 kb long in Saccharomyces cerevisiae. , 2015, ACS synthetic biology.

[64]  J. Wendland,et al.  Breeding of lager yeast with Saccharomyces cerevisiae improves stress resistance and fermentation performance , 2012, Yeast.

[65]  Carola Engler,et al.  A One Pot, One Step, Precision Cloning Method with High Throughput Capability , 2008, PloS one.

[66]  Zhaoyue Wang,et al.  Recombinant industrial brewing yeast strains with ADH2 interruption using self-cloning GSH1+CUP1 cassette. , 2009, FEMS yeast research.

[67]  J. Teixeira,et al.  Yeast: the soul of beer’s aroma—a review of flavour-active esters and higher alcohols produced by the brewing yeast , 2014, Applied Microbiology and Biotechnology.

[68]  P. Dostálek,et al.  Surface-engineered Saccharomyces cerevisiae displaying α-acetolactate decarboxylase from Acetobacter aceti ssp xylinum , 2016, Biotechnology Letters.

[69]  T. Becker,et al.  A New Validation of Relevant Substances for the Evaluation of Beer Aging Depending on the Employed Boiling System , 2010 .

[70]  Zhaoyue Wang,et al.  Integrated expression of the α-amylase, dextranase and glutathione gene in an industrial brewer’s yeast strain , 2011, World Journal of Microbiology and Biotechnology.

[71]  D. G. Gibson,et al.  Synthesis of DNA fragments in yeast by one-step assembly of overlapping oligonucleotides , 2009, Nucleic acids research.

[72]  Jay D Keasling,et al.  BglBricks: A flexible standard for biological part assembly , 2010, Journal of biological engineering.

[73]  S. Wunderlich,et al.  Consumer perception of genetically modified organisms and sources of information. , 2015, Advances in nutrition.

[74]  S. Yamano,et al.  Construction of a brewer's yeast having alpha-acetolactate decarboxylase gene from Acetobacter aceti ssp. xylinum integrated in the genome. , 1994, Journal of biotechnology.

[75]  Huimin Zhao,et al.  Directed evolution of a highly efficient cellobiose utilizing pathway in an industrial Saccharomyces cerevisiae strain , 2013, Biotechnology and bioengineering.

[76]  Simon C. Lovell,et al.  Sequencing and Characterisation of Rearrangements in Three S. pastorianus Strains Reveals the Presence of Chimeric Genes and Gives Evidence of Breakpoint Reuse , 2013, PloS one.

[77]  C. Landry,et al.  Complex Ancestries of Lager-Brewing Hybrids Were Shaped by Standing Variation in the Wild Yeast Saccharomyces eubayanus , 2016, PLoS genetics.

[78]  J. Pátková,et al.  Very high gravity wort fermentation by immobilised yeast , 2000, Biotechnology Letters.

[79]  L. Mattinen,et al.  Adaptive evolution of the lager brewing yeast Saccharomyces pastorianus for improved growth under hyperosmotic conditions and its influence on fermentation performance. , 2013, FEMS yeast research.

[80]  Roberto Pérez-Torrado,et al.  Genetic improvement of non-GMO wine yeasts: Strategies, advantages and safety , 2015 .

[81]  Huimin Zhao,et al.  Combinatorial Design of a Highly Efficient Xylose-Utilizing Pathway in Saccharomyces cerevisiae for the Production of Cellulosic Biofuels , 2012, Applied and Environmental Microbiology.

[82]  Jessica M Walter,et al.  CRISPR‐Cas‐Assisted Multiplexing (CAM): Simple Same‐Day Multi‐Locus Engineering in Yeast , 2016, Journal of cellular physiology.

[83]  F. Rudolf,et al.  Saccharomyces cerevisiae Shuttle vectors , 2017, Yeast.

[84]  F. Omura.  Targeting of mitochondrial Saccharomyces cerevisiae Ilv5p to the cytosol and its effect on vicinal diketone formation in brewing , 2008, Applied Microbiology and Biotechnology.

[85]  R. Ortíz-López,et al.  Genome annotation of a Saccharomyces sp. lager brewer's yeast , 2016, Genomics data.

[86]  A. C. Chang,et al.  Construction of biologically functional bacterial plasmids in vitro. , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[87]  C. Fadda,et al.  Is it possible to create an innovative craft durum wheat beer with sourdough yeasts? A case study , 2015 .

[88]  P. Dostálek,et al.  Biotransformations and biological activities of hop flavonoids. , 2015, Biotechnology advances.

[89]  C. T. Hittinger,et al.  Efficient engineering of marker-free synthetic allotetraploids of Saccharomyces. , 2016, Fungal genetics and biology : FG & B.

[90]  T. Sasaki,et al.  Breeding of a Brewer's Yeast Possessing Anticontaminant Properties , 1984 .

[91]  C. Blanco,et al.  Comparison of carbonyl profiles from Czech and Spanish lagers: Traditional and modern technology , 2016 .

[92]  Max G Schubert,et al.  Efficient Multiplexed Integration of Synergistic Alleles and Metabolic Pathways in Yeasts via CRISPR-Cas. , 2015, Cell systems.

[93]  George M. Church,et al.  Genome engineering in Saccharomyces cerevisiae using CRISPR-Cas systems , 2013, Nucleic acids research.

[94]  U. Bond.  Chapter 6: The genomes of lager yeasts. , 2009, Advances in applied microbiology.

[95]  F. Rudolf,et al.  A shuttle vector series for precise genetic engineering of Saccharomyces cerevisiae , 2016, Yeast.

[96]  J. Woolford,et al.  Ribosome Biogenesis in the Yeast Saccharomyces cerevisiae , 2013, Genetics.

[97]  Hal S. Alper,et al.  The development and characterization of synthetic minimal yeast promoters , 2015, Nature Communications.

[98]  A. Kondo,et al.  Expression of varied GFPs in Saccharomyces cerevisiae: codon optimization yields stronger than expected expression and fluorescence intensity , 2016, Scientific Reports.

[99]  J. Hansen,et al.  The level of MXR1 gene expression in brewing yeast during beer fermentation is a major determinant for the concentration of dimethyl sulfide in beer. , 2002, FEMS yeast research.

[100]  J. Londesborough,et al.  Maltotriose utilization in lager yeast strains: MTT1 encodes a maltotriose transporter , 2005, Yeast.

[101]  T. James,et al.  Lager yeasts possess dynamic genomes that undergo rearrangements and gene amplification in response to stress , 2008, Current Genetics.

[102]  C. Gaillardin,et al.  Analysis of the constitution of the beer yeast genome by PCR, sequencing and subtelomeric sequence hybridization. , 2001, International journal of systematic and evolutionary microbiology.

[103]  A. Granell,et al.  GoldenBraid: An Iterative Cloning System for Standardized Assembly of Reusable Genetic Modules , 2011, PloS one.

[104]  Sylvestre Marillonnet,et al.  Golden Gate cloning. , 2014, Methods in molecular biology.

[105]  P. Dostálek,et al.  Application of a hop by‐product in brewing: reduction in the level of haze‐active prolamines and improved antioxidant properties of the beer , 2014 .

[106]  T. Seppänen-Laakso,et al.  Inheritance of brewing-relevant phenotypes in constructed Saccharomyces cerevisiae × Saccharomyces eubayanus hybrids , 2017, Microbial Cell Factories.

[107]  Thomas Jeffries,et al.  Shuffling of Promoters for Multiple Genes To Optimize Xylose Fermentation in an Engineered Saccharomyces cerevisiae Strain , 2007, Applied and Environmental Microbiology.

[108]  Gavin Sherlock,et al.  Genetic Manipulation of Brewing Yeasts: Challenges and Opportunities , 2017 .

[109]  Huimin Zhao,et al.  Iowa State University From the SelectedWorks of Zengyi Shao 2012 Cloning and characterization of a panel of constitutive promoters for applications in pathway engineering in Saccharomyces cerevisiae , 2017 .

[110]  William C. Deloache,et al.  A Highly Characterized Yeast Toolkit for Modular, Multipart Assembly. , 2015, ACS synthetic biology.

[111]  Huimin Zhao,et al.  DNA assembler: a synthetic biology tool for characterizing and engineering natural product gene clusters. , 2012, Methods in enzymology.

[112]  C. Bamforth,et al.  Effects of Sulfur Dioxide and Polyvinylpolypyrrolidone on the Flavor Stability of Beer as Measured by Sensory and Chemical Analysis , 2003 .

[113]  J. Kalinowski,et al.  Towards systems metabolic engineering in Pichia pastoris. , 2017, Biotechnology advances.

[114]  J. Prieto,et al.  Engineering baker's yeast: room for improvement. , 1999, Trends in biotechnology.

[115]  Christian Weber,et al.  Cytosolic re-localization and optimization of valine synthesis and catabolism enables inseased isobutanol production with the yeast Saccharomyces cerevisiae , 2012, Biotechnology for Biofuels.

[116]  T. Becker,et al.  Self-cloning brewing yeast: a new dimension in beverage production , 2013, European Food Research and Technology.

[117]  Tom Ellis,et al.  DNA assembly for synthetic biology: from parts to pathways and beyond. , 2011, Integrative biology : quantitative biosciences from nano to macro.

[118]  D. Xiao,et al.  Decreased proteinase A excretion by strengthening its vacuolar sorting and weakening its constitutive secretion in Saccharomyces cerevisiae , 2016, Journal of Industrial Microbiology & Biotechnology.

[119]  T. G. Villa,et al.  Cloning and characterization of the beer foaming gene CFG1 from Saccharomyces pastorianus. , 2012, Journal of agricultural and food chemistry.

[120]  U. Stahl,et al.  Increasing sulphite formation in Saccharomyces cerevisiae by overexpression of MET14 and SSU1 , 2002, Yeast.

[121]  Narendra Maheshri,et al.  Harnessing mutagenic homologous recombination for targeted mutagenesis in vivo by TaGTEAM , 2013, Nucleic acids research.

[122]  K. Verstrepen,et al.  Phenotypic diversity of Flo protein family-mediated adhesion in Saccharomyces cerevisiae. , 2009, FEMS yeast research.

[123]  K. Verstrepen,et al.  Expression Levels of the Yeast Alcohol Acetyltransferase Genes ATF1, Lg-ATF1, and ATF2 Control the Formation of a Broad Range of Volatile Esters , 2003, Applied and Environmental Microbiology.

[124]  P. Sigsgaard,et al.  Construction of a hybrid brewing strain of saccharomyces carlsbergensis by mating of meiotic segregants , 1981 .

[125]  D. Voytas,et al.  Transposable elements and genome organization: a comprehensive survey of retrotransposons revealed by the complete Saccharomyces cerevisiae genome sequence. , 1998, Genome research.

[126]  L. Ruohonen,et al.  Maltose and maltotriose utilisation by group I strains of the hybrid lager yeast Saccharomyces pastorianus , 2016, FEMS yeast research.

[127]  T. Kunz,et al.  Relationship of iso‐α‐acid content and endogenous antioxidative potential during storage of lager beer , 2014 .

[128]  Erminio Monteleone,et al.  Influence of information about manufacturing process on beer acceptability , 2004 .

[129]  G. Marchant,et al.  A new window of opportunity to reject process-based biotechnology regulation. , 2015, GM crops & food.

[130]  Pedro Almeida,et al.  Distinct Domestication Trajectories in Top-Fermenting Beer Yeasts and Wine Yeasts , 2016, Current Biology.

[131]  V. Vidgren,et al.  New lager yeast strains generated by interspecific hybridization , 2015, Journal of Industrial Microbiology & Biotechnology.

[132]  T. Itoh,et al.  Next-generation sequencing analysis of lager brewing yeast strains reveals the evolutionary history of interspecies hybridization , 2016, DNA research : an international journal for rapid publication of reports on genes and genomes.

[133]  I. Pretorius,et al.  Controlled Expression of the Dominant Flocculation Genes FLO1, FLO5, and FLO11 in Saccharomyces cerevisiae , 2008, Applied and Environmental Microbiology.

[134]  Z Zhang,et al.  Plasmid stability in recombinant Saccharomyces cerevisiae. , 1996, Biotechnology advances.

[135]  K. Verstrepen,et al.  Large-Scale Selection and Breeding To Generate Industrial Yeasts with Superior Aroma Production , 2014, Applied and Environmental Microbiology.

[136]  Guangyi Zhang,et al.  Constructing an amylolytic brewing yeast Saccharomyces pastorianus suitable for accelerated brewing. , 2004, Journal of bioscience and bioengineering.

[137]  M. Burton,et al.  Consumer attitudes towards genetic modification, functional foods, and microorganisms: a choice modeling experiment for beer , 2002 .

[138]  Hal S Alper,et al.  Short Synthetic Terminators for Improved Heterologous Gene Expression in Yeast. , 2015, ACS synthetic biology.

[139]  K. L. Zimmermann,et al.  Public perceptions of agri-food applications of genetic modification - a systematic review and meta-analysis , 2013 .

[140]  J. Thevelein,et al.  Natural and modified promoters for tailored metabolic engineering of the yeast Saccharomyces cerevisiae. , 2014, Methods in molecular biology.

[141]  David Vogel,et al.  The Politics of Precaution: Regulating Health, Safety, and Environmental Risks in Europe and the United States , 2012 .

[142]  T. Ogata,et al.  Chromosomal structures of bottom fermenting yeasts. , 1999, Systematic and applied microbiology.

[143]  D. Xiao,et al.  Diacetyl content reduction in industrial brewer’s yeast through ILV2 disruption and BDH1 expression , 2016, European Food Research and Technology.

[144]  R. Bhatia,et al.  Risks and Precautions of Genetically Modified Organisms , 2011 .

[145]  Induction of production and secretion β(1→4) glucanase with Saccharomyces cerevesiae by replacing the MET10 gene with egl1 gene from Trichoderma reesei , 2009, Letters in applied microbiology.

[146]  J. Aguilera,et al.  Principles for the risk assessment of genetically modified microorganisms and their food products in the European Union. , 2013, International journal of food microbiology.

[147]  Guy Baele,et al.  Domestication and Divergence of Saccharomyces cerevisiae Beer Yeasts , 2006, Cell.

[148]  Wolfgang Kunze,et al.  Technology Brewing and malting , 1999 .

[149]  A. Dudley,et al.  Allelic Variation, Aneuploidy, and Nongenetic Mechanisms Suppress a Monogenic Trait in Yeast , 2014, Genetics.

[150]  Xuejing Bai,et al.  Secretion expression of SOD1 and its overlapping function with GSH in brewing yeast strain for better flavor and anti-aging ability , 2014, Journal of Industrial Microbiology & Biotechnology.

[151]  I. Russell,et al.  Innovations in Alcoholic Beverage Production , 2015 .

[152]  M. Granvogl,et al.  Studies on the Simultaneous Formation of Aroma-Active and Toxicologically Relevant Vinyl Aromatics from Free Phenolic Acids during Wheat Beer Brewing. , 2016, Journal of agricultural and food chemistry.

[153]  A. Mizuno,et al.  Beer brewing using a fusant between a sake yeast and a brewer's yeast. , 2001, Journal of bioscience and bioengineering.

[154]  Anton Glieder,et al.  Carbon source dependent promoters in yeasts , 2014, Microbial Cell Factories.

[155]  Carolien Martijn,et al.  Acceptance of genetically modified foods: The relation between technology and evaluation , 2008, Appetite.

[156]  Masahira Hattori,et al.  Genome Sequence of the Lager Brewing Yeast, an Interspecies Hybrid , 2009, DNA research : an international journal for rapid publication of reports on genes and genomes.

[157]  J Craig Venter,et al.  One-step assembly in yeast of 25 overlapping DNA fragments to form a complete synthetic Mycoplasma genitalium genome , 2008, Proceedings of the National Academy of Sciences.

[158]  Huimin Zhao,et al.  Construction and engineering of large biochemical pathways via DNA assembler. , 2013, Methods in molecular biology.

[159]  J. Hansen,et al.  Saccharomyces carlsbergensis contains two functional MET2 alleles similar to homologues from S. cerevisiae and S. monacensis. , 1994, Gene.

[160]  K. Kristiansen,et al.  Saccharomyces carlsbergensis contains two functional genes encoding the Acyl‐CoA binding protein, one similar to the ACB1 gene from S. cerevisiae and one identical to the ACB1 gene from S. monacensis , 1997, Yeast.

[161]  I. Pretorius,et al.  Co-expression of a Saccharomyces diastaticus glucoamylase-encoding gene and a Bacillus amyloliquefaciens alpha-amylase-encoding gene in Saccharomyces cerevisiae. , 1991, Gene.

[162]  Qi Li,et al.  Domesticating brewing yeast for decreasing acetaldehyde production and improving beer flavor stability , 2014, European Food Research and Technology.

[163]  K. Tanaka,et al.  Diversity of the HO gene encoding an endonuclease for mating‐type conversion in the bottom fermenting yeast Saccharomyces pastorianus , 2000, Yeast.

[164]  M. Pedersen.  DNA sequence polymorphisms in the genus saccharomyces III. Restriction endonuclease fragment patterns of chromosomal regions in brewing and other yeast strains , 1986 .

[165]  T. Brányik,et al.  The role of physicochemical interactions and FLO genes expression in the immobilization of industrially important yeasts by adhesion. , 2011, Colloids and surfaces. B, Biointerfaces.

[166]  S. Yamano,et al.  Cloning and expression of the gene encoding α-acetolactate decarboxylase from Acetobacter aceti ssp. xylinum in brewer's yeast , 1994 .

[167]  Haiyong Wang,et al.  Genome shuffling to improve fermentation properties of top-fermenting yeast by the improvement of stress tolerance , 2010 .

[168]  K. Kavanagh,et al.  Application of protoplast fusion to the nonconventional yeast , 1996 .

[169]  Hal S Alper,et al.  Characterization of plasmid burden and copy number in Saccharomyces cerevisiae for optimization of metabolic engineering applications. , 2013, FEMS yeast research.

[170]  Gene assembly and combinatorial libraries in S. cerevisiae via reiterative recombination. , 2013, Methods in molecular biology.

[171]  G. Stewart,et al.  125th Anniversary Review: Developments in brewing and distilling yeast strains , 2013 .

[172]  E. V. Soares.  Flocculation in Saccharomyces cerevisiae: a review , 2011, Journal of applied microbiology.

[173]  E. Beinrohr,et al.  Determination of Total Sulphur Dioxide in Beer Samples by Flow-Through Chronopotentiometry , 2006 .

[174]  M. Penttilä,et al.  Chromosomal Integration and Expression of Two Bacterial α-Acetolactate Decarboxylase Genes in Brewer's Yeast , 1991, Applied and environmental microbiology.

[175]  Mikko Arvas,et al.  Ploidy influences the functional attributes of de novo lager yeast hybrids , 2016, Applied Microbiology and Biotechnology.

[176]  P. Gonçalves,et al.  Population structure and reticulate evolution of Saccharomyces eubayanus and its lager‐brewing hybrids , 2014, Molecular ecology.

[177]  J. Hansen,et al.  Inactivation of MET10 in brewer's yeast specifically increases SO2 formation during beer production , 1996, Nature Biotechnology.

[178]  A. Iwamatsu,et al.  Molecular cloning, sequence analysis, and expression of the yeast alcohol acetyltransferase gene , 1994, Applied and environmental microbiology.

[179]  Zengyi Shao,et al.  DNA assembler, an in vivo genetic method for rapid construction of biochemical pathways , 2008, Nucleic acids research.

[180]  R. Parker,et al.  The link between adjacent codon pairs and mRNA stability , 2017, BMC Genomics.

[181]  P. Dostálek,et al.  Antioxidant Properties of Free, Soluble Ester and Insoluble‐Bound Phenolic Compounds in Different Barley Varieties and Corresponding Malts , 2008 .

[182]  U. Bond,et al.  Brewing up a storm: The genomes of lager yeasts and how they evolved. , 2017, Biotechnology advances.

[183]  Huimin Zhao,et al.  Customized optimization of metabolic pathways by combinatorial transcriptional engineering , 2012, Nucleic acids research.

[184]  J. Pronk,et al.  One-step assembly and targeted integration of multigene constructs assisted by the I-SceI meganuclease in Saccharomyces cerevisiae , 2013, FEMS yeast research.

[185]  Wujiu Zhang,et al.  Disruption of Brewer's Yeast Alcohol Dehydrogenase II Gene and Reduction of Acetaldehyde Content during Brewery Fermentation , 2006 .

[186]  J. Wendland,et al.  Genome Sequence of Saccharomyces carlsbergensis, the World’s First Pure Culture Lager Yeast , 2014, G3: Genes, Genomes, Genetics.

[187]  Antonio G. Cordente,et al.  A breeding strategy to harness flavor diversity of Saccharomyces interspecific hybrids and minimize hydrogen sulfide production. , 2012, FEMS yeast research.

[188]  J. Keasling,et al.  Lipid engineering reveals regulatory roles for membrane fluidity in yeast flocculation and oxygen-limited growth. , 2017, Metabolic engineering.

[189]  P. Barré,et al.  Cloning and analysis of a FLO5 flocculation gene from S. cerevisiae , 1994, Current Genetics.

[190]  Paul J. Chambers,et al.  Microbiological approaches to lowering ethanol concentration in wine , 2010 .

[191]  V. Siewers.  An overview on selection marker genes for transformation of Saccharomyces cerevisiae. , 2014, Methods in molecular biology.

[192]  N. D. Da Silva,et al.  Introduction and expression of genes for metabolic engineering applications in Saccharomyces cerevisiae. , 2012, FEMS yeast research.

[193]  Naoto Urano,et al.  Conversion of a non-flocculent brewer's yeast to flocculent ones by electrofusion: 2. Small-scale brewing by fusants , 1993 .

[194]  L. Ruohonen,et al.  Improved Fermentation Performance of a Lager Yeast after Repair of Its AGT1 Maltose and Maltotriose Transporter Genes , 2009, Applied and Environmental Microbiology.

[195]  Y. Kaneko,et al.  Co‐existence of two types of chromosome in the bottom fermenting yeast, Saccharomyces pastorianus , 1998, Yeast.

[196]  J. Nielsen,et al.  Alleviation of glucose repression of maltose metabolism by MIG1 disruption in Saccharomyces cerevisiae , 1996, Applied and environmental microbiology.

[197]  J. Pronk,et al.  Efficient simultaneous excision of multiple selectable marker cassettes using I-SceI-induced double-strand DNA breaks in Saccharomyces cerevisiae. , 2014, FEMS yeast research.

[198]  Jurgen F. Nijkamp,et al.  Chromosomal Copy Number Variation in Saccharomyces pastorianus Is Evidence for Extensive Genome Dynamics in Industrial Lager Brewing Strains , 2015, Applied and Environmental Microbiology.

[199]  Yang-Hoon Kim,et al.  Bioethanol production by a flocculent hybrid, CHFY0321 obtained by protoplast fusion between Saccharomyces cerevisiae and Saccharomyces bayanus , 2010 .

[200]  Hal S Alper,et al.  Use of expression-enhancing terminators in Saccharomyces cerevisiae to increase mRNA half-life and improve gene expression control for metabolic engineering applications. , 2013, Metabolic engineering.

[201]  T. James,et al.  Aneuploidy and copy number breakpoints in the genome of lager yeasts mapped by microarray hybridisation , 2004, Current Genetics.

[202]  Markus J. Herrgård,et al.  EasyCloneMulti: A Set of Vectors for Simultaneous and Multiple Genomic Integrations in Saccharomyces cerevisiae , 2016, PloS one.

[203]  M. Penttilä,et al.  Molecular cloning and analysis of the yeast flocculation gene FLO1 , 1994, Yeast.

[204]  M. Gastl,et al.  Reduction of toxicologically relevant styrene in wheat beer using specially produced wheat and barley malts , 2017, European Food Research and Technology.

[205]  G. W. Hatfield,et al.  A vector set for systematic metabolic engineering in Saccharomyces cerevisiae , 2011, Yeast.

[206]  K. Sigler,et al.  The phenomenon of Czech beer: a review. , 2018 .

[207]  A. Querol,et al.  Molecular Characterization of New Natural Hybrids of Saccharomyces cerevisiae and S. kudriavzevii in Brewing , 2008, Applied and Environmental Microbiology.

[208]  J. B. D. A. Silva,et al.  Production of alcohol-free beer with elevated amounts of flavouring compounds using lager yeast mutants , 2013 .

[209]  E. Louis,et al.  New yeasts—new brews: modern approaches to brewing yeast design and development , 2017, FEMS yeast research.

[210]  R. Akada.  Genetically modified industrial yeast ready for application. , 2002, Journal of bioscience and bioengineering.

[211]  K. Kondo,et al.  Nucleotide sequence and expression of the Enterobacter aerogenes alpha-acetolactate decarboxylase gene in brewer's yeast , 1988, Applied and environmental microbiology.

[212]  H. Ko,et al.  Construction of dextrin and isomaltose-assimilating brewer’s yeasts for production of low-carbohydrate beer , 2014, Biotechnology Letters.

[213]  L. Šilhánková.  Yeast mutants excreting vitamin B1 and their use in the production of thiamine rich beers , 1985 .

[214]  Zhaoyue Wang,et al.  Construction of amylolytic industrial brewing yeast strain with high glutathione content for manufacturing beer with improved anti-staling capability and flavor. , 2010, Journal of microbiology and biotechnology.

[215]  Huimin Zhao,et al.  Directed evolution of a cellobiose utilization pathway in Saccharomyces cerevisiae by simultaneously engineering multiple proteins , 2013, Microbial Cell Factories.

[216]  E. Nevoigt,et al.  Genetic engineering of brewing yeast to reduce the content of ethanol in beer. , 2002, FEMS yeast research.

[217]  P. Margalith,et al.  Interspecific protoplast fusion of Saccharomyces cerevisiae and Saccharomyces mellis , 1983, European Journal of Applied Microbiology and Biotechnology.

[218]  Jay D Keasling,et al.  CasEMBLR: Cas9-Facilitated Multiloci Genomic Integration of in Vivo Assembled DNA Parts in Saccharomyces cerevisiae. , 2015, ACS synthetic biology.

[219]  C. Lopes,et al.  Evaluation of different genetic procedures for the generation of artificial hybrids in Saccharomyces genus for winemaking. , 2012, International journal of food microbiology.

[220]  K. K. Thomsen,et al.  Processing and secretion of barley (1–3, 1–4)-β-glucanase in yeast , 1989 .

[221]  J. Keasling,et al.  High-level semi-synthetic production of the potent antimalarial artemisinin , 2013, Nature.

[222]  H. Shimizu,et al.  Stable disruption of ethanol production by deletion of the genes encoding alcohol dehydrogenase isozymes in Saccharomyces cerevisiae. , 2012, Journal of bioscience and bioengineering.

[223]  D. Greig,et al.  Saccharomyces cerevisiae: a nomadic yeast with no niche? , 2015, FEMS yeast research.

[224]  F. Bai,et al.  Evidence for a Far East Asian origin of lager beer yeast , 2014, Current Biology.

[225]  J. Nielsen,et al.  Advances in metabolic engineering of yeast Saccharomyces cerevisiae for production of chemicals , 2014, Biotechnology journal.

[226]  Virginia W Cornish,et al.  Reiterative Recombination for the in vivo assembly of libraries of multigene pathways , 2011, Proceedings of the National Academy of Sciences.

[227]  V. Siewers,et al.  A systems-level approach for metabolic engineering of yeast cell factories. , 2012, FEMS yeast research.

[228]  H. Yoshimoto,et al.  Acetate ester production by Saccharomyces cerevisiae lacking the ATF1 gene encoding the alcohol acetyltransferase , 1996 .

[229]  J. Teixeira,et al.  Continuous beer fermentation diacetyl as a villain , 2015 .

[230]  H. Čížková,et al.  Determination of free amino acids in beers: A comparison of Czech and foreign brands , 2008 .

[231]  A. Fujita,et al.  Engineering of Yeast Put4 Permease and Its Application to Lager Yeast for Efficient Proline Assimilation , 2005, Bioscience, biotechnology, and biochemistry.

[232]  Rainer Fischer,et al.  The CRISPR/Cas9 system for plant genome editing and beyond. , 2015, Biotechnology advances.

[233]  Chris Boulton,et al.  Brewing: Science and Practice , 2004 .

[234]  T. Ashikari,et al.  Isolation and Characterization of a Gene Specific to Lager Brewing Yeast That Encodes a Branched-Chain Amino Acid Permease , 2001, Applied and Environmental Microbiology.

[235]  H. Cherest,et al.  Two divergent MET10 genes, one from Saccharomyces cerevisiae and one from Saccharomyces carlsbergensis, encode the alpha subunit of sulfite reductase and specify potential binding sites for FAD and NADPH , 1994, Journal of bacteriology.

[236]  V. Siewers,et al.  Advances in yeast genome engineering. , 2014, FEMS yeast research.