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The roles of galactitol, galactose‐1‐phosphate, and phosphoglucomutase in galactose‐induced toxicity in Saccharomyces cerevisiae

The roles of galactitol, galactose‐1‐phosphate, and phosphoglucomutase in galactose‐induced... The uptake and catabolism of galactose by the yeast Saccharomyces cerevisiae is much lower than for glucose and fructose, and in applications of this yeast for utilization of complex substrates that contain galactose, for example, lignocellulose and raffinose, this causes prolonged fermentations. Galactose is metabolized via the Leloir pathway, and besides the industrial interest in improving the flux through this pathway it is also of medical relevance to study the Leloir pathway. Thus, genetic disorders in the genes encoding galactose‐1‐phosphate uridylyltransferase or galactokinase result in galactose toxicity both in patients with galactosemia and in yeast. In order to elucidate galactose related toxicity, which may explain the low uptake and catabolic rates of S. cerevisiae, we have studied the physiological characteristics and intracellular metabolite profiles of recombinant S. cerevisiae strains with improved or impaired growth on galactose. Aerobic batch cultivations on galactose of strains with different combinations of overexpression of the genes GAL1, GAL2, GAL7, and GAL10, which encode proteins that together convert extracellular galactose into glucose‐1‐phosphate, revealed a decrease in the maximum specific growth rate when compared to the reference strain. The hypothesized toxic intermediate galactose‐1‐phosphate cannot be the sole cause of galactose related toxicity, but indications were found that galactose‐1‐phosphate might cause a negative effect through inhibition of phosphoglucomutase. Furthermore, we show that galactitol is formed in S. cerevisiae, and that the combination of elevated intracellular galactitol concentration, and the ratio between galactose‐1‐phosphate concentration and phosphoglucomutase activity seems to be important for galactose related toxicity causing decreased growth rates. Biotechnol. Bioeng. 2008;101: 317–326. © 2008 Wiley Periodicals, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Biotechnology and Bioengineering Wiley

The roles of galactitol, galactose‐1‐phosphate, and phosphoglucomutase in galactose‐induced toxicity in Saccharomyces cerevisiae

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References (58)

Publisher
Wiley
Copyright
Copyright © 2008 Wiley Periodicals, Inc., A Wiley Company
ISSN
0006-3592
eISSN
1097-0290
DOI
10.1002/bit.21890
pmid
18421797
Publisher site
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Abstract

The uptake and catabolism of galactose by the yeast Saccharomyces cerevisiae is much lower than for glucose and fructose, and in applications of this yeast for utilization of complex substrates that contain galactose, for example, lignocellulose and raffinose, this causes prolonged fermentations. Galactose is metabolized via the Leloir pathway, and besides the industrial interest in improving the flux through this pathway it is also of medical relevance to study the Leloir pathway. Thus, genetic disorders in the genes encoding galactose‐1‐phosphate uridylyltransferase or galactokinase result in galactose toxicity both in patients with galactosemia and in yeast. In order to elucidate galactose related toxicity, which may explain the low uptake and catabolic rates of S. cerevisiae, we have studied the physiological characteristics and intracellular metabolite profiles of recombinant S. cerevisiae strains with improved or impaired growth on galactose. Aerobic batch cultivations on galactose of strains with different combinations of overexpression of the genes GAL1, GAL2, GAL7, and GAL10, which encode proteins that together convert extracellular galactose into glucose‐1‐phosphate, revealed a decrease in the maximum specific growth rate when compared to the reference strain. The hypothesized toxic intermediate galactose‐1‐phosphate cannot be the sole cause of galactose related toxicity, but indications were found that galactose‐1‐phosphate might cause a negative effect through inhibition of phosphoglucomutase. Furthermore, we show that galactitol is formed in S. cerevisiae, and that the combination of elevated intracellular galactitol concentration, and the ratio between galactose‐1‐phosphate concentration and phosphoglucomutase activity seems to be important for galactose related toxicity causing decreased growth rates. Biotechnol. Bioeng. 2008;101: 317–326. © 2008 Wiley Periodicals, Inc.

Journal

Biotechnology and Bioengineering – Wiley

Published: Oct 1, 2008

Keywords: galactitol; galactose toxicity; galactosemia; phosphoglucomutase; galactose‐1‐phosphate; intracellular metabolites

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