Glycolic acid production in the engineered yeasts Saccharomyces cerevisiae and Kluyveromyces lactis

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Glycolic acid production in the engineered yeasts Saccharomyces cerevisiae and Kluyveromyces lactis. / Koivistoinen, Outi M.; Kuivanen, Joosu; Barth, Dorothee; Turkia, Heidi; Pitkanen, Juha-Pekka; Penttila, Merja; Richard, Peter.

In: MICROBIAL CELL FACTORIES, Vol. 12, 82, 23.09.2013.

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Koivistoinen, Outi M. ; Kuivanen, Joosu ; Barth, Dorothee ; Turkia, Heidi ; Pitkanen, Juha-Pekka ; Penttila, Merja ; Richard, Peter. / Glycolic acid production in the engineered yeasts Saccharomyces cerevisiae and Kluyveromyces lactis. In: MICROBIAL CELL FACTORIES. 2013 ; Vol. 12.

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@article{22734dcb9bc747d3b55dca3e258630a5,
title = "Glycolic acid production in the engineered yeasts Saccharomyces cerevisiae and Kluyveromyces lactis",
abstract = "Background: Glycolic acid is a C2 hydroxy acid that is a widely used chemical compound. It can be polymerised to produce biodegradable polymers with excellent gas barrier properties. Currently, glycolic acid is produced in a chemical process using fossil resources and toxic chemicals. Biotechnological production of glycolic acid using renewable resources is a desirable alternative.Results: The yeasts Saccharomyces cerevisiae and Kluyveromyces lactis are suitable organisms for glycolic acid production since they are acid tolerant and can grow in the presence of up to 50 g l(-1) glycolic acid. We engineered S. cerevisiae and K. lactis for glycolic acid production using the reactions of the glyoxylate cycle to produce glyoxylic acid and then reducing it to glycolic acid. The expression of a high affinity glyoxylate reductase alone already led to glycolic acid production. The production was further improved by deleting genes encoding malate synthase and the cytosolic form of isocitrate dehydrogenase. The engineered S. cerevisiae strain produced up to about 1 g l(-1) of glycolic acid in a medium containing D-xylose and ethanol. Similar modifications in K. lactis resulted in a much higher glycolic acid titer. In a bioreactor cultivation with D-xylose and ethanol up to 15 g l(-1) of glycolic acid was obtained.Conclusions: This is the first demonstration of engineering yeast to produce glycolic acid. Prior to this work glycolic acid production through the glyoxylate cycle has only been reported in bacteria. The benefit of a yeast host is the possibility for glycolic acid production also at low pH, which was demonstrated in flask cultivations. Production of glycolic acid was first shown in S. cerevisiae. To test whether a Crabtree negative yeast would be better suited for glycolic acid production we engineered K. lactis in the same way and demonstrated it to be a better host for glycolic acid production.",
keywords = "Glycolic acid, Glyoxylic acid, Metabolic engineering, Glyoxylate cycle, Glyoxylate reductase, Saccharomyces cerevisiae, Kluyveromyces lactis, SNF1 PROTEIN-KINASE, ARABIDOPSIS-GLYOXYLATE REDUCTASE, ISOCITRATE LYASE, BUDDING YEAST, CATABOLITE INACTIVATION, SUBSTRATE-SPECIFICITY, NUCLEOTIDE-SEQUENCE, ESCHERICHIA-COLI, SYNTHASE GENES, BAKERS-YEAST",
author = "Koivistoinen, {Outi M.} and Joosu Kuivanen and Dorothee Barth and Heidi Turkia and Juha-Pekka Pitkanen and Merja Penttila and Peter Richard",
year = "2013",
month = "9",
day = "23",
doi = "10.1186/1475-2859-12-82",
language = "English",
volume = "12",
journal = "MICROBIAL CELL FACTORIES",
issn = "1475-2859",
publisher = "BioMed Central",

}

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TY - JOUR

T1 - Glycolic acid production in the engineered yeasts Saccharomyces cerevisiae and Kluyveromyces lactis

AU - Koivistoinen, Outi M.

AU - Kuivanen, Joosu

AU - Barth, Dorothee

AU - Turkia, Heidi

AU - Pitkanen, Juha-Pekka

AU - Penttila, Merja

AU - Richard, Peter

PY - 2013/9/23

Y1 - 2013/9/23

N2 - Background: Glycolic acid is a C2 hydroxy acid that is a widely used chemical compound. It can be polymerised to produce biodegradable polymers with excellent gas barrier properties. Currently, glycolic acid is produced in a chemical process using fossil resources and toxic chemicals. Biotechnological production of glycolic acid using renewable resources is a desirable alternative.Results: The yeasts Saccharomyces cerevisiae and Kluyveromyces lactis are suitable organisms for glycolic acid production since they are acid tolerant and can grow in the presence of up to 50 g l(-1) glycolic acid. We engineered S. cerevisiae and K. lactis for glycolic acid production using the reactions of the glyoxylate cycle to produce glyoxylic acid and then reducing it to glycolic acid. The expression of a high affinity glyoxylate reductase alone already led to glycolic acid production. The production was further improved by deleting genes encoding malate synthase and the cytosolic form of isocitrate dehydrogenase. The engineered S. cerevisiae strain produced up to about 1 g l(-1) of glycolic acid in a medium containing D-xylose and ethanol. Similar modifications in K. lactis resulted in a much higher glycolic acid titer. In a bioreactor cultivation with D-xylose and ethanol up to 15 g l(-1) of glycolic acid was obtained.Conclusions: This is the first demonstration of engineering yeast to produce glycolic acid. Prior to this work glycolic acid production through the glyoxylate cycle has only been reported in bacteria. The benefit of a yeast host is the possibility for glycolic acid production also at low pH, which was demonstrated in flask cultivations. Production of glycolic acid was first shown in S. cerevisiae. To test whether a Crabtree negative yeast would be better suited for glycolic acid production we engineered K. lactis in the same way and demonstrated it to be a better host for glycolic acid production.

AB - Background: Glycolic acid is a C2 hydroxy acid that is a widely used chemical compound. It can be polymerised to produce biodegradable polymers with excellent gas barrier properties. Currently, glycolic acid is produced in a chemical process using fossil resources and toxic chemicals. Biotechnological production of glycolic acid using renewable resources is a desirable alternative.Results: The yeasts Saccharomyces cerevisiae and Kluyveromyces lactis are suitable organisms for glycolic acid production since they are acid tolerant and can grow in the presence of up to 50 g l(-1) glycolic acid. We engineered S. cerevisiae and K. lactis for glycolic acid production using the reactions of the glyoxylate cycle to produce glyoxylic acid and then reducing it to glycolic acid. The expression of a high affinity glyoxylate reductase alone already led to glycolic acid production. The production was further improved by deleting genes encoding malate synthase and the cytosolic form of isocitrate dehydrogenase. The engineered S. cerevisiae strain produced up to about 1 g l(-1) of glycolic acid in a medium containing D-xylose and ethanol. Similar modifications in K. lactis resulted in a much higher glycolic acid titer. In a bioreactor cultivation with D-xylose and ethanol up to 15 g l(-1) of glycolic acid was obtained.Conclusions: This is the first demonstration of engineering yeast to produce glycolic acid. Prior to this work glycolic acid production through the glyoxylate cycle has only been reported in bacteria. The benefit of a yeast host is the possibility for glycolic acid production also at low pH, which was demonstrated in flask cultivations. Production of glycolic acid was first shown in S. cerevisiae. To test whether a Crabtree negative yeast would be better suited for glycolic acid production we engineered K. lactis in the same way and demonstrated it to be a better host for glycolic acid production.

KW - Glycolic acid

KW - Glyoxylic acid

KW - Metabolic engineering

KW - Glyoxylate cycle

KW - Glyoxylate reductase

KW - Saccharomyces cerevisiae

KW - Kluyveromyces lactis

KW - SNF1 PROTEIN-KINASE

KW - ARABIDOPSIS-GLYOXYLATE REDUCTASE

KW - ISOCITRATE LYASE

KW - BUDDING YEAST

KW - CATABOLITE INACTIVATION

KW - SUBSTRATE-SPECIFICITY

KW - NUCLEOTIDE-SEQUENCE

KW - ESCHERICHIA-COLI

KW - SYNTHASE GENES

KW - BAKERS-YEAST

U2 - 10.1186/1475-2859-12-82

DO - 10.1186/1475-2859-12-82

M3 - Article

VL - 12

JO - MICROBIAL CELL FACTORIES

JF - MICROBIAL CELL FACTORIES

SN - 1475-2859

M1 - 82

ER -

ID: 9226729