title: Metabolic engineering of Saccharomyces cerevisiae for the biotechnological production of succinic acid.
abstract: The production of bio-based succinic acid is receiving great attention, and several predominantly prokaryotic organisms have been evaluated for this purpose. In this study we report on the suitability of the highly acid- and osmotolerant yeast Saccharomyces cerevisiae as a succinic acid production host. We implemented a metabolic engineering strategy for the oxidative production of succinic acid in yeast by deletion of the genes SDH1, SDH2, IDH1 and IDP1. The engineered strains harbor a TCA cycle that is completely interrupted after the intermediates isocitrate and succinate. The strains show no serious growth constraints on glucose. In glucose-grown shake flask cultures, the quadruple deletion strain Δsdh1Δsdh2Δidh1Δidp1 produces succinic acid at a titer of 3.62 g L(-1) (factor 4.8 compared to wild-type) at a yield of 0.11 mol (mol glucose)(-1). Succinic acid is not accumulated intracellularly. This makes the yeast S. cerevisiae a suitable and promising candidate for the biotechnological production of succinic acid on an industrial scale.
authors.affiliation: Berlin University of Technology, Institute for Biotechnology, Department of Microbiology and Genetics, Gustav-Meyer-Allee 25, D-13355 Berlin, Germany.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Raab
authors.forename: Gabi
authors.initials: G
authors.lastname: Gebhardt
authors.forename: Natalia
authors.initials: N
authors.lastname: Bolotina
authors.forename: Dirk
authors.initials: D
authors.lastname: Weuster-Botz
authors.forename: Christine
authors.initials: C
authors.lastname: Lang
mesh_terms: D057005:Bioengineering; D018533:Biomass; D003470:Culture Media; D005110:Extracellular Space / Q000378:metabolism; D017353:Gene Deletion; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006038:Glyoxylates / Q000378:metabolism; D007218:Industrial Microbiology; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D019802:Succinic Acid / Q000378:metabolism*
chemical_list: D003470:Culture Media; D006038:Glyoxylates; C528541:SDH1 protein, S cerevisiae; C541941:SDH2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D018698:Glutamic Acid; D019802:Succinic Acid; D007521:Isocitrate Dehydrogenase; C039355:isocitrate dehydrogenase (NADP+); D013385:Succinate Dehydrogenase; D005947:Glucose; C031150:glyoxylic acid