Essential Role of One-carbon Metabolism and Gcn4p and Bas1p Transcriptional Regulators during Adaptation to Anaerobic Growth of Saccharomyces cerevisiae*
- Bonny M. Tsoi‡§,
- Anthony G. Beckhouse§1,
- Cristy L. Gelling§,
- Mark J. Raftery¶,
- Joyce Chiu§,
- Abraham M. Tsoi§,
- Lars Lauterbach§2,
- Peter J. Rogers∥,
- Vincent J. Higgins‡ and
- Ian W. Dawes§3
- ‡School of Biomedical and Health Sciences, University of Western Sydney, Penrith, New South Wales DC 1791, the §Ramaciotti Centre for Gene Function Analysis, School of Biotechnology and Biomolecular Science, and the ¶Bioanalytical Mass Spectrometry Facilities, University of New South Wales, Sydney 2052, and ∥Foster's Group Limited, 4-6 Southampton Crescent, Abbotsford 3067, Australia
- 3 To whom correspondence should be addressed. Tel.: 61-2-9385-2089; Fax: 61-2-9385-1050; E-mail: i.dawes{at}unsw.edu.au.
Abstract
The transcriptional activator Gcn4p is considered the master regulator of amino acid metabolism in Saccharomyces cerevisiae and is required for the transcriptional response to amino acid starvation. Here it is shown that Gcn4p plays a previously undescribed role in regulating adaptation to anaerobic growth. A gcn4 mutant exhibited a highly extended lag phase after a shift to anaerobiosis that was the result of l-serine depletion. In addition, the one-carbon metabolism and purine biosynthesis transcriptional regulator Bas1p were strictly required for anaerobic growth on minimal medium, and this was similarly due to l-serine limitation in bas1 mutants. The induction of one-carbon metabolism during anaerobiosis is needed to increase the supply of l-serine from the glycine and threonine pathways. Using a number of experimental approaches, we demonstrate that these transcription regulators play vital roles in regulating l-serine biosynthesis in the face of increased demand during adaptation to anaerobiosis. This increased l-serine requirement is most likely due to anaerobic remodeling of the cell wall, involving de novo synthesis of a large number of very serine-rich mannoproteins and an increase in the total serine content of the cell wall. During anaerobic starvation for l-serine, this essential amino acid is preferentially directed to the cell wall, indicating the existence of a regulatory mechanism to balance competing cellular demands.
Footnotes
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↵4 The abbreviations used are: H4folate, tetrahydrofolate; GCRE, general control-responsive element; 5,10-CH2-H4folate, 5,10-methylene tetrahydrofolate; SD, synthetic defined medium; MS, mass spectrometry; MS/MS, tandem MS.
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↵* This work was supported by Linkage and Discovery Grants from the Australian Research Council (to I. W. D., V. J. H., and P. J. R.) and by Australian Research Council Postgraduate Awards (to B. M. T., C. L. G., A. M. T., and A. G. B.).
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The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1 and S2 and Tables S1–S3.
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↵1 Present address: Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane 4111, Australia.
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↵2 Present address: Institute of Biology/Microbiology, Humboldt-Universität zu Berlin, Chausseestrasse 117, Berlin 10115, Germany.
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- Received December 9, 2008.
- Revision received February 10, 2009.
- The American Society for Biochemistry and Molecular Biology, Inc.
