Quantitative trait analysis of yeast biodiversity yields novel gene tools for metabolic engineering
Autor: | Luigi Concilio, Jorge Duitama, Steve Swinnen, Thiago M. Pais, Maria R. Foulquié-Moreno, Johan M. Thevelein, Georg Hubmann, Sofie Saerens, Kevin J. Verstrepen, Elke Nevoigt, Lotte Mathé, Huyen Thi Nguyen, Nicolas Meurens, Jean-Claude de Troostembergh |
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Rok vydání: | 2012 |
Předmět: |
Glycerol
Saccharomyces cerevisiae Proteins Quantitative Trait Loci Bioengineering Single-nucleotide polymorphism Locus (genetics) Saccharomyces cerevisiae Biology Quantitative trait locus Applied Microbiology and Biotechnology Metabolic engineering 03 medical and health sciences Genetic variation Genetic variability Allele 030304 developmental biology Genetics 0303 health sciences Ethanol 030306 microbiology Structural gene Chromosome Mapping Genetic Variation Biodiversity Metabolic Engineering Biotechnology |
Zdroj: | Metabolic Engineering |
ISSN: | 1096-7184 |
Popis: | Engineering of metabolic pathways by genetic modification has been restricted largely to enzyme-encoding structural genes. The product yield of such pathways is a quantitative genetic trait. Out of 52 Saccharomyces cerevisiae strains phenotyped in small-scale fermentations, we identified strain CBS6412 as having unusually low glycerol production and higher ethanol yield as compared to an industrial reference strain. We mapped the QTLs underlying this quantitative trait with pooled-segregant whole-genome sequencing using 20 superior segregants selected from a total of 257. Plots of SNP variant frequency against SNP chromosomal position revealed one major and one minor locus. Downscaling of the major locus and reciprocal hemizygosity analysis identified an allele of SSK1, ssk1(E330N…K356N), expressing a truncated and partially mistranslated protein, as causative gene. The diploid CBS6412 parent was homozygous for ssk1(E330N…K356N). This allele affected growth and volumetric productivity less than the gene deletion. Introduction of the ssk1(E330N…K356N) allele in the industrial reference strain resulted in stronger reduction of the glycerol/ethanol ratio compared to SSK1 deletion and also compromised volumetric productivity and osmotolerance less. Our results show that polygenic analysis of yeast biodiversity can provide superior novel gene tools for metabolic engineering. |
Databáze: | OpenAIRE |
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