{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:00:48Z","timestamp":1790650848785,"version":"4.1.0"},"reference-count":82,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:00:00Z","timestamp":1635811200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:00:00Z","timestamp":1635811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003130","name":"fonds wetenschappelijk onderzoek","doi-asserted-by":"publisher","award":["12W3918N"],"award-info":[{"award-number":["12W3918N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004727","name":"vlaams instituut voor biotechnologie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004727","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010563","name":"fonds baillet latour","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010563","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012331","name":"agentschap innoveren en ondernemen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012331","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"european research council","doi-asserted-by":"publisher","award":["CoG682009"],"award-info":[{"award-number":["CoG682009"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"european research council","doi-asserted-by":"publisher","award":["959109"],"award-info":[{"award-number":["959109"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biotechnol Biofuels"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The brewer\u2019s yeast <jats:italic>Saccharomyces cerevisiae<\/jats:italic> is exploited in several industrial processes, ranging from food and beverage fermentation to the production of biofuels, pharmaceuticals and complex chemicals. The large genetic and phenotypic diversity within this species offers a formidable natural resource to obtain superior strains, hybrids, and variants. However, most industrially relevant traits in <jats:italic>S<\/jats:italic>. <jats:italic>cerevisiae<\/jats:italic> strains are controlled by multiple genetic loci. Over the past years, several studies have identified some of these QTLs. However, because these studies only focus on a limited set of traits and often use different techniques and starting strains, a global view of industrially relevant QTLs is still missing.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Here, we combined the power of 1125 fully sequenced inbred segregants with high-throughput phenotyping methods to identify as many as 678 QTLs across 18 different traits relevant to industrial fermentation processes, including production of ethanol, glycerol, isobutanol, acetic acid, sulfur dioxide, flavor-active esters, as well as resistance to ethanol, acetic acid, sulfite and high osmolarity. We identified and confirmed several variants that are associated with multiple different traits, indicating that many QTLs are pleiotropic. Moreover, we show that both rare and common variants, as well as variants located in coding and non-coding regions all contribute to the phenotypic variation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our findings represent an important step in our understanding of the genetic underpinnings of industrially relevant yeast traits and open new routes to study complex genetics and genetic interactions as well as to engineer novel, superior industrial yeasts. Moreover, the major role of rare variants suggests that there is a plethora of different combinations of mutations that can be explored in genome editing.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13068-021-02059-w","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T18:39:30Z","timestamp":1635878370000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Massive QTL analysis identifies pleiotropic genetic determinants for stress resistance, aroma formation, and ethanol, glycerol and isobutanol production in Saccharomyces cerevisiae"],"prefix":"10.1186","volume":"14","author":[{"given":"Ping-Wei","family":"Ho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supinya","family":"Piampongsant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigida","family":"Gallone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Del Cortona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter-Jan","family":"Peeters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Reijbroek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jules","family":"Verbaet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Herrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen","family":"Cortebeeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robbe","family":"Nolmans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veerle","family":"Saels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Steensels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel F.","family":"Jarosz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3077-6219","authenticated-orcid":false,"given":"Kevin J.","family":"Verstrepen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,2]]},"reference":[{"issue":"6","key":"2059_CR1","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.1016\/j.cell.2016.08.020","volume":"166","author":"B Gallone","year":"2016","unstructured":"Gallone B, Steensels J, Prahl T, Soriaga L, Saels V, Herrera-Malaver B, et al. Domestication and divergence of saccharomyces cerevisiae beer yeasts. Cell. 2016;166(6):1397-1410.e16.","journal-title":"Cell"},{"issue":"10","key":"2059_CR2","doi-asserted-by":"publisher","first-page":"R381","DOI":"10.1016\/j.cub.2019.04.025","volume":"29","author":"J Steensels","year":"2019","unstructured":"Steensels J, Gallone B, Voordeckers K, Verstrepen KJ. Domestication of industrial microbes. Curr Biol. 2019;29(10):R381\u201393.","journal-title":"Curr Biol"},{"issue":"1","key":"2059_CR3","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1371\/journal.pgen.0010005","volume":"1","author":"JC Fay","year":"2005","unstructured":"Fay JC, Benavides JA. Evidence for domesticated and wild populations of Saccharomyces cerevisiae. PLoS Genet. 2005;1(1):66\u201371.","journal-title":"PLoS Genet"},{"issue":"7236","key":"2059_CR4","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nature07743","volume":"458","author":"G Liti","year":"2009","unstructured":"Liti G, Carter DM, Moses AM, Warringer J, Parts L, James SA, et al. Population genomics of domestic and wild yeasts. Nature. 2009;458(7236):337\u201341.","journal-title":"Nature"},{"key":"2059_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2164-9-524","volume":"9","author":"L Carreto","year":"2008","unstructured":"Carreto L, Eiriz MF, Gomes AC, Pereira PM, Schuller D, Santos MAS. Comparative genomics of wild type yeast strains unveils important genome diversity. BMC Genomics. 2008;9:1\u201317.","journal-title":"BMC Genomics"},{"issue":"11","key":"2059_CR6","doi-asserted-by":"publisher","first-page":"1562","DOI":"10.1038\/s41559-019-0997-9","volume":"3","author":"B Gallone","year":"2019","unstructured":"Gallone B, Steensels J, Mertens S, Dzialo MC, Gordon JL, Wauters R, et al. Interspecific hybridization facilitates niche adaptation in beer yeast. Nat Ecol Evol. 2019;3(11):1562\u201375.","journal-title":"Nat Ecol Evol"},{"key":"2059_CR7","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1146\/annurev-micro-091213-113025","volume":"68","author":"J Steensels","year":"2014","unstructured":"Steensels J, Verstrepen KJ. Taming wild yeast: Potential of conventional and nonconventional yeasts in industrial fermentations. Annu Rev Microbiol. 2014;68:61\u201380.","journal-title":"Annu Rev Microbiol"},{"issue":"5","key":"2059_CR8","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1111\/1574-6976.12073","volume":"38","author":"J Steensels","year":"2014","unstructured":"Steensels J, Snoek T, Meersman E, Nicolino MP, Voordeckers K, Verstrepen KJ. Improving industrial yeast strains: exploiting natural and artificial diversity. FEMS Microbiol Rev. 2014;38(5):947\u201395.","journal-title":"FEMS Microbiol Rev"},{"issue":"18","key":"2059_CR9","doi-asserted-by":"publisher","first-page":"6166","DOI":"10.1128\/AEM.00133-15","volume":"81","author":"E Meersman","year":"2015","unstructured":"Meersman E, Steensels J, Paulus T, Struyf N, Saels V, Mathawan M, et al. Breeding strategy to generate robust yeast starter cultures for cocoa pulp fermentations. Appl Environ Microbiol. 2015;81(18):6166\u201376.","journal-title":"Appl Environ Microbiol"},{"issue":"2","key":"2059_CR10","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1016\/j.cell.2018.08.057","volume":"175","author":"E Sharon","year":"2018","unstructured":"Sharon E, Chen S-AA, Khosla NM, Smith JD, Pritchard JK, Fraser HB. Functional genetic variants revealed by massively parallel precise genome editing. Cell. 2018;175(2):544\u201357.","journal-title":"Cell"},{"issue":"6289","key":"2059_CR11","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1126\/science.aaf5124","volume":"352","author":"MJ Sadhu","year":"2016","unstructured":"Sadhu MJ, Bloom JS, Day L, Kruglyak L. CRISPR-directed mitotic recombination enables genetic mapping without crosses. Science (New York, NY). 2016;352(6289):1113\u20136.","journal-title":"Science (New York, NY)"},{"issue":"6","key":"2059_CR12","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1038\/nbt.4137","volume":"36","author":"KR Roy","year":"2018","unstructured":"Roy KR, Smith JD, Vonesch SC, Lin G, Tu CS, Lederer AR, et al. Multiplexed precision genome editing with trackable genomic barcodes in yeast. Nat Biotechnol. 2018;36(6):512\u201320.","journal-title":"Nat Biotechnol"},{"key":"2059_CR13","doi-asserted-by":"publisher","first-page":"6","DOI":"10.3389\/fgene.2019.00683","volume":"10","author":"E Peltier","year":"2019","unstructured":"Peltier E, Friedrich A, Schacherer J, Marullo P. Quantitative trait nucleotides impacting the technological performances of industrial saccharomyces cerevisiae strains. Front Genet. 2019;10:6.","journal-title":"Front Genet"},{"issue":"10","key":"2059_CR14","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1038\/nrg3937","volume":"16","author":"A Long","year":"2015","unstructured":"Long A, Liti G, Luptak A, Tenaillon O. Elucidating the molecular architecture of adaptation via evolve and resequence experiments. Nat Rev Genet. 2015;16(10):567\u201382.","journal-title":"Nat Rev Genet"},{"key":"2059_CR15","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.copbio.2017.10.011","volume":"50","author":"R Mans","year":"2018","unstructured":"Mans R, Daran JMG, Pronk JT. Under pressure: evolutionary engineering of yeast strains for improved performance in fuels and chemicals production. Curr Opin Biotechnol. 2018;50:47\u201356.","journal-title":"Curr Opin Biotechnol"},{"issue":"August","key":"2059_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ymben.2019.08.004","volume":"56","author":"TE Sandberg","year":"2019","unstructured":"Sandberg TE, Salazar MJ, Weng LL, Palsson BO, Feist AM. The emergence of adaptive laboratory evolution as an efficient tool for biological discovery and industrial biotechnology. Metab Eng. 2019;56(August):1\u201316.","journal-title":"Metab Eng"},{"issue":"11","key":"2059_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pgen.1005635","volume":"11","author":"K Voordeckers","year":"2015","unstructured":"Voordeckers K, Kominek J, Das A, Espinosa-Cant\u00fa A, De Maeyer D, Arslan A, et al. Adaptation to high ethanol reveals complex evolutionary pathways. PLoS Genet. 2015;11(11):1\u201331.","journal-title":"PLoS Genet"},{"issue":"1","key":"2059_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13068-016-0696-6","volume":"10","author":"PW Ho","year":"2017","unstructured":"Ho PW, Swinnen S, Duitama J, Nevoigt E. The sole introduction of two single-point mutations establishes glycerol utilization in Saccharomyces cerevisiae CENPK derivatives. Biotechnol Biofuels. 2017;10(1):1\u201315.","journal-title":"Biotechnol Biofuels"},{"issue":"8","key":"2059_CR19","first-page":"1823","volume":"35","author":"CJ Huang","year":"2018","unstructured":"Huang CJ, Lu MY, Chang YW, Li WH. Experimental evolution of yeast for high-temperature tolerance. Mol Biol Evol. 2018;35(8):1823\u201339.","journal-title":"Mol Biol Evol"},{"issue":"5","key":"2059_CR20","doi-asserted-by":"publisher","first-page":"1572","DOI":"10.1073\/pnas.0408709102","volume":"102","author":"RB Brem","year":"2005","unstructured":"Brem RB, Kruglyak L. The landscape of genetic complexity across 5,700 gene expression traits in yeast. Proc Natl Acad Sci USA. 2005;102(5):1572\u20137.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"11","key":"2059_CR21","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1038\/nrg1964","volume":"7","author":"MV Rockman","year":"2006","unstructured":"Rockman MV, Kruglyak L. Genetics of global gene expression. Nat Rev Genet. 2006;7(11):862\u201372.","journal-title":"Nat Rev Genet"},{"issue":"6878","key":"2059_CR22","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/416326a","volume":"416","author":"LM Steinmetz","year":"2002","unstructured":"Steinmetz LM, Sinha H, Richards DR, Spiegelman JI, Oefner PJ, McCusker JH, et al. Dissecting the architecture of a quantitative trait locus in yeast. Nature. 2002;416(6878):326\u201330.","journal-title":"Nature"},{"key":"2059_CR23","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1371\/journal.pgen.1002912","volume":"8","author":"G Liti","year":"2012","unstructured":"Liti G, Louis EJ. Advances in quantitative trait analysis in yeast. PLoS Genet. 2012;8:8.","journal-title":"PLoS Genet"},{"issue":"1\u20132","key":"2059_CR24","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1007\/s10681-005-1681-5","volume":"142","author":"BCY Collard","year":"2005","unstructured":"Collard BCY, Jahufer MZZ, Brouwer JB, Pang ECK. An introduction to markers, quantitative trait loci (QTL) mapping and marker-assisted selection for crop improvement: The basic concepts. Euphytica. 2005;142(1\u20132):169\u201396.","journal-title":"Euphytica"},{"key":"2059_CR25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2164-15-207","volume":"15","author":"J Duitama","year":"2014","unstructured":"Duitama J, S\u00e1nchez-Rodr\u00edguez A, Goovaerts A, Pulido-Tamayo S, Hubmann G, Foulqui\u00e9-Moreno MR, et al. Improved linkage analysis of Quantitative Trait Loci using bulk segregants unveils a novel determinant of high ethanol tolerance in yeast. BMC Genomics. 2014;15:1.","journal-title":"BMC Genomics"},{"issue":"7","key":"2059_CR26","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1101\/gr.116731.110","volume":"21","author":"L Parts","year":"2011","unstructured":"Parts L, Cubillos FA, Warringer J, Jain K, Salinas F, Bumpstead SJ, et al. Revealing the genetic structure of a trait by sequencing a population under selection. Genome Res. 2011;21(7):1131\u20138.","journal-title":"Genome Res"},{"issue":"1","key":"2059_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13068-015-0421-x","volume":"9","author":"JP Meijnen","year":"2016","unstructured":"Meijnen JP, Randazzo P, Foulqui\u00e9-Moreno MR, Van Den Brink J, Vandecruys P, Stojiljkovic M, et al. Polygenic analysis and targeted improvement of the complex trait of high acetic acid tolerance in the yeast Saccharomyces cerevisiae. Biotechnol Biofuels. 2016;9(1):1\u201318.","journal-title":"Biotechnol Biofuels"},{"issue":"1","key":"2059_CR28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13068-020-01761-5","volume":"13","author":"M Stojiljkovic","year":"2020","unstructured":"Stojiljkovic M, Foulqui\u00e9-Moreno MR, Thevelein JM. Polygenic analysis of very high acetic acid tolerance in the yeast Saccharomyces cerevisiae reveals a complex genetic background and several new causative alleles. Biotechnol Biofuels. 2020;13(1):1\u201327.","journal-title":"Biotechnol Biofuels"},{"issue":"3","key":"2059_CR29","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1534\/genetics.106.065292","volume":"175","author":"XH Hu","year":"2007","unstructured":"Hu XH, Wang MH, Tan T, Li JR, Yang H, Leach L, et al. Genetic dissection of ethanol tolerance in the budding yeast Saccharomyces cerevisiae. Genetics. 2007;175(3):1479\u201387.","journal-title":"Genetics"},{"issue":"5","key":"2059_CR30","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1101\/gr.131698.111","volume":"22","author":"S Swinnen","year":"2012","unstructured":"Swinnen S, Schaerlaekens K, Pais T, Claesen J, Hubmann G, Yang Y, et al. Identification of novel causative genes determining the complex trait of high ethanol tolerance in yeast using pooled-segregant whole-genome sequence analysis. Genome Res. 2012;22(5):975\u201384.","journal-title":"Genome Res"},{"issue":"1","key":"2059_CR31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12864-018-4562-8","volume":"19","author":"M Eder","year":"2018","unstructured":"Eder M, Sanchez I, Brice C, Camarasa C, Legras JL, Dequin S. QTL mapping of volatile compound production in Saccharomyces cerevisiae during alcoholic fermentation. BMC Genomics. 2018;19(1):1\u201319.","journal-title":"BMC Genomics"},{"issue":"7436","key":"2059_CR32","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/nature11867","volume":"494","author":"JS Bloom","year":"2013","unstructured":"Bloom JS, Ehrenreich IM, Loo WT, Lite TLV, Kruglyak L. Finding the sources of missing heritability in a yeast cross. Nature. 2013;494(7436):234\u20137.","journal-title":"Nature"},{"issue":"1","key":"2059_CR33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1558-5646.2011.01486.x","volume":"66","author":"MV Rockman","year":"2012","unstructured":"Rockman MV. The QTN program and the alleles that matter for evolution: All that\u2019s gold does not glitter. Evolution. 2012;66(1):1\u201317.","journal-title":"Evolution"},{"issue":"3","key":"2059_CR34","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1016\/j.cell.2017.12.015","volume":"172","author":"R She","year":"2018","unstructured":"She R, Jarosz DF. Mapping Causal Variants with Single-Nucleotide Resolution Reveals Biochemical Drivers of Phenotypic Change. Cell. 2018;172(3):478-490.e15.","journal-title":"Cell"},{"issue":"5","key":"2059_CR35","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/j.cels.2019.04.002","volume":"8","author":"CM Jakobson","year":"2019","unstructured":"Jakobson CM, Jarosz DF. Molecular origins of complex heritability in natural genotype-to-phenotype relationships. Cell Syst. 2019;8(5):363\u201379.","journal-title":"Cell Syst"},{"issue":"1","key":"2059_CR36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-019-09166-1","volume":"10","author":"CM Jakobson","year":"2019","unstructured":"Jakobson CM, She R, Jarosz DF. Pervasive function and evidence for selection across standing genetic variation in S cerevisiae. Nat Commun. 2019;10(1):1\u201313.","journal-title":"Nat Commun"},{"key":"2059_CR37","first-page":"8","volume":"5","author":"J Peter","year":"2018","unstructured":"Peter J, De Chiara M, Friedrich A, Yue J-X, Pflieger D, Bergstr\u00f6m A, et al. Genome evolution across 1,011 Saccharomyces cerevisiae isolates Species-wide genetic and phenotypic diversity. Nature. 2018;5:8.","journal-title":"Nature"},{"key":"2059_CR38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15294\/lifesci.v8i1.29984","volume":"8","author":"T Fournier","year":"2019","unstructured":"Fournier T, Saada OA, Hou J, Peter J, Caudal E, Schacherer J. Extensive impact of low-frequency variants on the phenotypic landscape at population-scale. Life. 2019;8:1\u201318.","journal-title":"Life"},{"issue":"2","key":"2059_CR39","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1093\/bfgp\/elv044","volume":"15","author":"DA Skelly","year":"2016","unstructured":"Skelly DA, Magwene PM. Population perspectives on functional genomic variation in yeast. Brief Funct Genomics. 2016;15(2):138\u201346.","journal-title":"Brief Funct Genomics"},{"issue":"June","key":"2059_CR40","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1038\/351652a0","volume":"351","author":"J McDonald","year":"1991","unstructured":"McDonald J, Kreitman M. Adaptive protein evolution at Adh in Drosophila. Nature. 1991;351(June):652\u20134.","journal-title":"Nature"},{"issue":"11","key":"2059_CR41","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1038\/nrg2207","volume":"8","author":"T Mitchell-Olds","year":"2007","unstructured":"Mitchell-Olds T, Willis JH, Goldstein DB. Which evolutionary processes influence natural genetic variation for phenotypic traits? Nat Rev Genet. 2007;8(11):845\u201356.","journal-title":"Nat Rev Genet"},{"issue":"21","key":"2059_CR42","doi-asserted-by":"publisher","first-page":"5412","DOI":"10.1111\/mec.13341","volume":"24","author":"P Almeida","year":"2015","unstructured":"Almeida P, Barbosa R, Zalar P, Imanishi Y, Shimizu K, Turchetti B, et al. A population genomics insight into the Mediterranean origins of wine yeast domestication. Mol Ecol. 2015;24(21):5412\u201327.","journal-title":"Mol Ecol"},{"issue":"4","key":"2059_CR43","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1007\/s00253-010-2707-z","volume":"87","author":"C Weber","year":"2010","unstructured":"Weber C, Farwick A, Benisch F, Brat D, Dietz H, Subtil T, et al. Trends and challenges in the microbial production of lignocellulosic bioalcohol fuels. Appl Microbiol Biotechnol. 2010;87(4):1303\u201315.","journal-title":"Appl Microbiol Biotechnol"},{"key":"2059_CR44","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.enzmictec.2016.09.004","volume":"96","author":"N Mohandesi","year":"2017","unstructured":"Mohandesi N, Haghbeen K, Ranaei O, Arab SS, Hassani S. Catalytic efficiency and thermostability improvement of Suc2 invertase through rational site-directed mutagenesis. Enzyme Microb Technol. 2017;96:14\u201322.","journal-title":"Enzyme Microb Technol"},{"issue":"35","key":"2059_CR45","doi-asserted-by":"publisher","first-page":"26815","DOI":"10.1074\/jbc.M110.145946","volume":"285","author":"MA Teste","year":"2010","unstructured":"Teste MA, Marie Fran\u00e7ois J, Parrou JL. Characterization of a new multigene family encoding isomaltases in the yeast Saccharomyces cerevisiae, the IMA family. J Biol Chem. 2010;285(35):26815\u201324.","journal-title":"J Biol Chem"},{"key":"2059_CR46","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1371\/journal.pbio.1001446","volume":"10","author":"K Voordeckers","year":"2012","unstructured":"Voordeckers K, Brown CA, Vanneste K, van der Zande E, Voet A, Maere S, et al. Reconstruction of ancestral metabolic enzymes reveals molecular mechanisms underlying evolutionary innovation through gene duplication. PLoS Biol. 2012;10:12.","journal-title":"PLoS Biol"},{"issue":"3","key":"2059_CR47","first-page":"213","volume":"42","author":"S Novak","year":"2004","unstructured":"Novak S, Zechner-Krpan V, Mari V. Maltose Transport and Metabolism in S cerevisiae. Ftb. 2004;42(3):213\u20138.","journal-title":"Ftb."},{"issue":"9","key":"2059_CR48","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1101\/gr.243147.118","volume":"29","author":"B Offei","year":"2019","unstructured":"Offei B, Vandecruys P, De Graeve S, Foulqui\u00e9-Moreno MR, Thevelein JM. Unique genetic basis of the distinct antibiotic potency of high acetic acid production in the probiotic yeast Saccharomyces cerevisiae var. Boulardii Genome Research. 2019;29(9):1478\u201394.","journal-title":"Boulardii Genome Research"},{"issue":"2","key":"2059_CR49","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1093\/oxfordjournals.jbchem.a129637","volume":"70","author":"K Umezu","year":"1971","unstructured":"Umezu K, Amaya T, Yoshimoto A, Tomita K. Purification and properties of orotidine-5\u2019-phosphate pyrophosphorylase and orotidine-5\u2019-phosphate decarboxylase from bakers\u2019 yeast. J Biochem. 1971;70(2):249\u201362.","journal-title":"J Biochem"},{"issue":"3","key":"2059_CR50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/nmicrobiol.2015.30","volume":"1","author":"MT Alam","year":"2016","unstructured":"Alam MT, Zelezniak A, M\u00fclleder M, Shliaha P, Schwarz R, Capuano F, et al. The metabolic background is a global player in Saccharomyces gene expression epistasis. Nat Microbiol. 2016;1(3):1\u201310.","journal-title":"Nat Microbiol"},{"issue":"7","key":"2059_CR51","first-page":"584","volume":"1","author":"P Niederberger","year":"1981","unstructured":"Niederberger P, Miozzari G, H\u00fctter R. Biological role of the general control of amino acid biosynthesis in Saccharomyces cerevisiae. Mol Cell Biol. 1981;1(7):584\u201393.","journal-title":"Mol Cell Biol"},{"key":"2059_CR52","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1371\/journal.pgen.1003548","volume":"9","author":"TM Pais","year":"2013","unstructured":"Pais TM, Foulqui\u00e9-Moreno MR, Hubmann G, Duitama J, Swinnen S, Goovaerts A, et al. Comparative Polygenic Analysis of Maximal Ethanol Accumulation Capacity and Tolerance to High Ethanol Levels of Cell Proliferation in Yeast. PLoS Genet. 2013;9:6.","journal-title":"PLoS Genet"},{"issue":"1","key":"2059_CR53","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/MMBR.67.1.1-15.2003","volume":"67","author":"GB Kohlhaw","year":"2003","unstructured":"Kohlhaw GB. Leucine Biosynthesis in Fungi: Entering Metabolism through the Back Door. Microbiol Mol Biol Rev. 2003;67(1):1\u201315.","journal-title":"Microbiol Mol Biol Rev"},{"issue":"8","key":"2059_CR54","doi-asserted-by":"publisher","first-page":"2259","DOI":"10.1128\/AEM.02625-07","volume":"74","author":"LA Hazelwood","year":"2008","unstructured":"Hazelwood LA, Daran JM, Van Maris AJA, Pronk JT, Dickinson JR. The Ehrlich pathway for fusel alcohol production: A century of research on Saccharomyces cerevisiae metabolism. Appl Environ Microbiol. 2008;74(8):2259\u201366.","journal-title":"Appl Environ Microbiol"},{"key":"2059_CR55","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1051\/matecconf\/201822501013","volume":"225","author":"E Erdiwansyah","year":"2018","unstructured":"Erdiwansyah E, Mamat R, Sani MSM, Khoerunnisa F, Sardjono RE, Ali O, et al. Effects of Diesel-Biodiesel Blends in Diesel Engine Single Cylinder on the Emission Characteristic. MATEC Web of Conferences. 2018;225:1\u20136.","journal-title":"MATEC Web of Conferences"},{"issue":"2","key":"2059_CR56","doi-asserted-by":"publisher","first-page":"S95","DOI":"10.1093\/femsre\/fux031","volume":"41","author":"MC Dzialo","year":"2017","unstructured":"Dzialo MC, Park R, Steensels J, Lievens B, Verstrepen KJ. Physiology, ecology and industrial applications of aroma formation in yeast. FEMS Microbiol Rev. 2017;41(2):S95-128.","journal-title":"FEMS Microbiol Rev"},{"issue":"9","key":"2059_CR57","doi-asserted-by":"publisher","first-page":"5228","DOI":"10.1128\/AEM.69.9.5228-5237.2003","volume":"69","author":"KJ Verstrepen","year":"2003","unstructured":"Verstrepen KJ, Van Laere SDM, Vanderhaegen BMP, Derdelinckx G, Dufour JP, Pretorius IS, 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. Appl Environ Microbiol. 2003;69(9):5228\u201337.","journal-title":"Appl Environ Microbiol"},{"issue":"2","key":"2059_CR58","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1111\/1751-7915.12488","volume":"10","author":"HD Goold","year":"2017","unstructured":"Goold HD, Kroukamp H, Williams TC, Paulsen IT, Varela C, Pretorius IS. Yeast\u2019s balancing act between ethanol and glycerol production in low-alcohol wines. Microb Biotechnol. 2017;10(2):264\u201378.","journal-title":"Microb Biotechnol"},{"issue":"4","key":"2059_CR59","doi-asserted-by":"publisher","first-page":"371","DOI":"10.5344\/ajev.2004.55.4.371","volume":"55","author":"DJ Erasmus","year":"2004","unstructured":"Erasmus DJ, Cliff M, van Vuuren HJJ. Impact of yeast strain on the production of acetic acid, glycerol, and the sensory attributes of icewine. Am J Enol Vitic. 2004;55(4):371\u20138.","journal-title":"Am J Enol Vitic"},{"issue":"1","key":"2059_CR60","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1128\/AEM.65.1.143-149.1999","volume":"65","author":"F Remize","year":"1999","unstructured":"Remize F, Roustan JL, Sablayrolles JM, Barre P, Dequin S. Glycerol overproduction by engineered Saccharomyces cerevisiae wine yeast strains leads to substantial changes in by-product formation and to a stimulation of fermentation rate in stationary phase. Appl Environ Microbiol. 1999;65(1):143\u20139.","journal-title":"Appl Environ Microbiol"},{"issue":"2","key":"2059_CR61","first-page":"450","volume":"65","author":"L Jespersen","year":"1999","unstructured":"Jespersen L, Cesar LB, Meaden PG. Multiple-Glucoside Transporter Genes in Brewer\u2019s. Yeast. 1999;65(2):450\u20136.","journal-title":"Yeast"},{"issue":"10","key":"2059_CR62","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/j.cub.2010.04.027","volume":"20","author":"CA Brown","year":"2010","unstructured":"Brown CA, Murray AW, Verstrepen KJ. Rapid expansion and functional divergence of subtelomeric gene families in yeasts. Curr Biol. 2010;20(10):895\u2013903.","journal-title":"Curr Biol"},{"issue":"1","key":"2059_CR63","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1134\/S1607672910030051","volume":"432","author":"DG Naumoff","year":"2010","unstructured":"Naumoff DG, Naumov GI. Discovery of a novel family of \u03b1-glucosidase IMA genes in yeast Saccharomyces cerevisiae. Dokl Biochem Biophys. 2010;432(1):114\u20136.","journal-title":"Dokl Biochem Biophys"},{"issue":"1","key":"2059_CR64","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/femsyr\/fox006","volume":"17","author":"WL Marques","year":"2017","unstructured":"Marques WL, Mans R, Marella ER, Cordeiro RL, van den Broek M, Daran JMG, et al. Elimination of sucrose transport and hydrolysis in Saccharomyces cerevisiae: A platform strain for engineering sucrose metabolism. FEMS Yeast Res. 2017;17(1):1\u201311.","journal-title":"FEMS Yeast Res"},{"issue":"3","key":"2059_CR65","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1002\/jib.145","volume":"120","author":"Y He","year":"2014","unstructured":"He Y, Dong J, Yin H, Zhao Y, Chen R, Wan X, et al. Wort composition and its impact on the flavour-active higher alcohol and ester formation of beer - A review. J Inst Brew. 2014;120(3):157\u201363.","journal-title":"J Inst Brew"},{"issue":"5","key":"2059_CR66","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1002\/j.2050-0416.1998.tb00998.x","volume":"104","author":"OS Younis","year":"1998","unstructured":"Younis OS, Stewart GG. Sugar uptake and subsequent ester and higher alcohol production by Saccharomyces cerevisiae. J Inst Brew. 1998;104(5):255\u201364.","journal-title":"J Inst Brew"},{"issue":"1","key":"2059_CR67","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/sj.jim.2900442","volume":"20","author":"H Alexandre","year":"1998","unstructured":"Alexandre H, Charpentier C. Biochemical aspects of stuck and sluggish fermentation in grape must. J Ind Microbiol Biotechnol. 1998;20(1):20\u20137.","journal-title":"J Ind Microbiol Biotechnol"},{"issue":"22","key":"2059_CR68","first-page":"1","volume":"10","author":"Y Su","year":"2020","unstructured":"Su Y, Zhang W, Zhang A, Shao W. Biorefinery: The production of isobutanol from biomass feedstocks. Applied Sciences (Switzerland). 2020;10(22):1\u201318.","journal-title":"Applied Sciences (Switzerland)"},{"issue":"1","key":"2059_CR69","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13068-019-1486-8","volume":"12","author":"J Wess","year":"2019","unstructured":"Wess J, Brinek M, Boles E. Improving isobutanol production with the yeast Saccharomyces cerevisiae by successively blocking competing metabolic pathways as well as ethanol and glycerol formation. Biotechnol Biofuels. 2019;12(1):1\u201315.","journal-title":"Biotechnol Biofuels"},{"issue":"3","key":"2059_CR70","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1007\/s002940050482","volume":"36","author":"JE Kurtz","year":"1999","unstructured":"Kurtz JE, Exinger F, Erbs P, Jund R. New insights into the pyrimidine salvage pathway of Saccharomyces cerevisiae: Requirement of six genes for cytidine metabolism. Curr Genet. 1999;36(3):130\u20136.","journal-title":"Curr Genet"},{"issue":"2\u20133","key":"2059_CR71","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/0378-1119(87)90131-4","volume":"57","author":"CS Hoffman","year":"1987","unstructured":"Hoffman CS, Winston F. A ten-minute DNA preparation from yeast efficiently releases autonomous plasmids for transformation of Escherichia coli. Gene. 1987;57(2\u20133):267\u201372.","journal-title":"Gene"},{"issue":"1","key":"2059_CR72","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/nprot.2007.13","volume":"2","author":"RD Gietz","year":"2007","unstructured":"Gietz RD, Schiestl RH. High-efficiency yeast transformation using the LiAc\/SS carrier DNA\/PEG method. Nat Protoc. 2007;2(1):31\u20134.","journal-title":"Nat Protoc"},{"issue":"22","key":"2059_CR73","doi-asserted-by":"publisher","first-page":"6965","DOI":"10.1128\/AEM.02235-14","volume":"80","author":"J Steensels","year":"2014","unstructured":"Steensels J, Meersman E, Snoek T, Saels V, Verstrepen KJ. Large-scale selection and breeding to generate industrial yeasts with superior aroma production. Appl Environ Microbiol. 2014;80(22):6965\u201375.","journal-title":"Appl Environ Microbiol"},{"key":"2059_CR74","first-page":"4","volume":"2","author":"O Wagih","year":"2014","unstructured":"Wagih O. Parts L gitter: a robust and accurate method for quantification of colony sizes from plate images. GBethesda. 2014;2:4.","journal-title":"GBethesda."},{"issue":"15","key":"2059_CR75","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","volume":"30","author":"AM Bolger","year":"2014","unstructured":"Bolger AM, Lohse M, Usadel B. Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30(15):2114\u201320.","journal-title":"Bioinformatics"},{"issue":"14","key":"2059_CR76","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","volume":"25","author":"H Li","year":"2009","unstructured":"Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25(14):1754\u201360.","journal-title":"Bioinformatics"},{"key":"2059_CR77","first-page":"178","volume":"201","author":"R Poplin","year":"2017","unstructured":"Poplin R, Ruano-Rubio V, DePristo M, Fennell T, Carneiro M, Van der Auwera G, et al. Scaling accurate genetic variant discovery to tens of thousands of samples. Biorxiv. 2017;201:178.","journal-title":"Biorxiv."},{"issue":"5","key":"2059_CR78","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1101\/gr.102970.109","volume":"20","author":"AR Quinlan","year":"2010","unstructured":"Quinlan AR, Clark RA, Sokolova S, Leibowitz ML, Zhang Y, Hurles ME, et al. Genome-wide mapping and assembly of structural variant breakpoints in the mouse genome. Genome Res. 2010;20(5):623\u201335.","journal-title":"Genome Res"},{"issue":"2","key":"2059_CR79","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1093\/bib\/bbs017","volume":"14","author":"H Thorvaldsd\u00f3ttir","year":"2013","unstructured":"Thorvaldsd\u00f3ttir H, Robinson JT, Mesirov JP. Integrative Genomics Viewer (IGV): High-performance genomics data visualization and exploration. Brief Bioinform. 2013;14(2):178\u201392.","journal-title":"Brief Bioinform"},{"issue":"2","key":"2059_CR80","doi-asserted-by":"publisher","first-page":"80","DOI":"10.4161\/fly.19695","volume":"6","author":"P Cingolani","year":"2012","unstructured":"Cingolani P, Platts A, Wang LL, Coon M, Nguyen T, Wang L, et al. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly. 2012;6(2):80\u201392.","journal-title":"Fly"},{"issue":"D1","key":"2059_CR81","doi-asserted-by":"publisher","first-page":"D447","DOI":"10.1093\/nar\/gku1003","volume":"43","author":"D Szklarczyk","year":"2015","unstructured":"Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, et al. STRING v10: Protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2015;43(D1):D447\u201352.","journal-title":"Nucleic Acids Res"},{"issue":"11","key":"2059_CR82","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498\u2013504.","journal-title":"Genome Res"}],"container-title":["Biotechnology for Biofuels"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13068-021-02059-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13068-021-02059-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13068-021-02059-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T07:05:12Z","timestamp":1675839912000},"score":1,"resource":{"primary":{"URL":"https:\/\/biotechnologyforbiofuels.biomedcentral.com\/articles\/10.1186\/s13068-021-02059-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,2]]},"references-count":82,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["2059"],"URL":"https:\/\/doi.org\/10.1186\/s13068-021-02059-w","relation":{},"ISSN":["1754-6834"],"issn-type":[{"value":"1754-6834","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,2]]},"assertion":[{"value":"15 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 October 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 November 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"211"}}