Overexpression of alpha-ketoglutarate dehydrogenase in Yarrowia lipolytica and its effect on production of organic acids

The yeast Yarrowia lipolytica is one of the most intensively studied “non-conventional” yeast species. Its ability to secrete various organic acids, like pyruvic (PA), citric, isocitric, and alpha-ketoglutaric (KGA) acid, in large amounts is of interest for biotechnological applications. We have stu...

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Bibliographic Details
Published in:Applied microbiology and biotechnology 2011-03, Vol.89 (5), p.1519-1526
Main Authors: Holz, Martina, Otto, Christina, Kretzschmar, Anne, Yovkova, Venelina, Aurich, Andreas, Pötter, Markus, Marx, Achim, Barth, Gerold
Format: Article
Language:English
Subjects:
Acid production
Acids
Alpha-ketoglutarate dehydrogenase
alpha-ketoglutaric acid
Applied Genetics and Molecular Biotechnology
Biological and medical sciences
Biomedical and Life Sciences
Biosynthesis
Biotechnology
Carbon
Carbon sources
Carboxylic Acids - metabolism
citric acid
Dehydrogenase
Dehydrogenases
Enzymes
Fundamental and applied biological sciences. Psychology
Gene Expression
Genes
Glycerol
Influence
isocitric acid
Ketoglutarate Dehydrogenase Complex - biosynthesis
Ketoglutarate Dehydrogenase Complex - genetics
Life Sciences
Microbial Genetics and Genomics
Microbiology
Organic acids
pyruvic acid
Recombinant Proteins - biosynthesis
Recombinant Proteins - genetics
Saccharomyces cerevisiae
Studies
Trace elements
Vitamin B
Yarrowia - enzymology
Yarrowia - genetics
Yarrowia lipolytica
Yeast
Yeasts
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Summary:The yeast Yarrowia lipolytica is one of the most intensively studied “non-conventional” yeast species. Its ability to secrete various organic acids, like pyruvic (PA), citric, isocitric, and alpha-ketoglutaric (KGA) acid, in large amounts is of interest for biotechnological applications. We have studied the effect of the alpha-ketoglutarate dehydrogenase (KGDH) complex on the production process of KGA. Being well studied in Saccharomyces cerevisiae this enzyme complex consists of three subunits: alpha-ketoglutarate dehydrogenase, dihydrolipoyl transsuccinylase, and lipoamide dehydrogenase. Here we report the effect of overexpression of these subunits encoding genes and resulting increase of specific KGDH activity on organic acid production under several conditions of growth limitation and an excess of carbon source in Y. lipolytica. The constructed strain containing multiple copies of all three KGDH genes showed a reduced production of KGA and an elevated production of PA under conditions of KGA production. However, an increased activity of the KGDH complex had no influence on organic acid production under citric acid production conditions.
ISSN:0175-7598
1432-0614
DOI:10.1007/s00253-010-2957-9