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Applied and Environmental Microbiology, May 2000, p. 1970-1973, Vol. 66, No. 5
0099-2240/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Redirection of the Respiro-Fermentative Flux Distribution in Saccharomyces cerevisiae by Overexpression of the Transcription Factor Hap4p

Jolanda Blom,1 M. Joost Teixeira De Mattos,2 and Leslie A. Grivell1,*

Section for Molecular Biology, Swammerdam Institute of Life Sciences, University of Amsterdam, 1098 SM Amsterdam,1 and Section for Microbiology, Swammerdam Institute of Life Sciences, University of Amsterdam,2 The Netherlands

Received 9 November 1999/Accepted 27 February 2000

Reduction of aerobic fermentation on sugars by altering the fermentative/oxidative balance is of significant interest for optimization of industrial production of Saccharomyces cerevisiae. Glucose control of oxidative metabolism in baker's yeast is partly mediated through transcriptional regulation of the Hap4p subunit of the Hap2/3/4/5p transcriptional activator complex. To alleviate glucose repression of oxidative metabolism, we constructed a yeast strain with constitutively elevated levels of Hap4p. Genetic analysis of expression levels of glucose-repressed genes and analysis of respiratory capacity showed that Hap4p overexpression (partly) relieves glucose repression of respiration. Analysis of the physiological properties of the Hap4p overproducer in batch cultures in fermentors (aerobic, glucose excess) has shown that the metabolism of this strain is more oxidative than in the wild-type strain, resulting in a significant reduced ethanol production and improvement of growth rate and a 40% gain in biomass yield. Our results show that modification of one or more transcriptional regulators can be a powerful and a widely applicable tool for redirection of metabolic fluxes in microorganisms.

* Corresponding author. Mailing address: Section for Molecular Biology, Swammerdam Institute of Life Sciences, University of Amsterdam, Kruislaan 318, 1098 SM Amsterdam, The Netherlands. Phone: 31 20 5257924. Fax: 31 20 6685086. E-mail: Grivell{at}bio.uva.nl.

Applied and Environmental Microbiology, May 2000, p. 1970-1973, Vol. 66, No. 5
0099-2240/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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