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Physiological and Transcriptional Responses of Saccharomyces cerevisiae to Zinc Limitation in Chemostat Cultures

Raffaele De Nicola,^1,, Lucie A. Hazelwood,^2,5, Erik A. F. De Hulster,^2,5 Michael C. Walsh,³ Theo A. Knijnenburg,^4,5 Marcel J. T. Reinders,^4,5 Graeme M. Walker,¹ Jack T. Pronk,^2,5 Jean-Marc Daran,^2,5 and Pascale Daran-Lapujade^2,5*

Yeast Research Group, Division of Molecular and Life Sciences, University of Abertay, Dundee DD1 1HG, Scotland,¹ Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC Delft, The Netherlands,² Heineken Supply Chain, Research and Innovation, Burgemeester Smeetsweg 1, 2380 BB Zoeterwoude, The Netherlands,³ Information and Communication Theory Group, Delft University of Technology, Mekelweg 4, 2628 CD Delft, The Netherlands,⁴ Kluyver Centre for Genomics of Industrial Fermentations, Julianalaan 67, 2628 BC Delft, The Netherlands⁵

Received 28 June 2007/ Accepted 4 October 2007

Transcriptional responses of the yeast Saccharomyces cerevisiae to Zn availability were investigated at a fixed specific growth rate under limiting and abundant Zn concentrations in chemostat culture. To investigate the context dependency of this transcriptional response and eliminate growth rate-dependent variations in transcription, yeast was grown under several chemostat regimens, resulting in various carbon (glucose), nitrogen (ammonium), zinc, and oxygen supplies. A robust set of genes that responded consistently to Zn limitation was identified, and the set enabled the definition of the Zn-specific Zap1p regulon, comprised of 26 genes and characterized by a broader zinc-responsive element consensus (MHHAACCBYNMRGGT) than so far described. Most surprising was the Zn-dependent regulation of genes involved in storage carbohydrate metabolism. Their concerted down-regulation was physiologically relevant as revealed by a substantial decrease in glycogen and trehalose cellular content under Zn limitation. An unexpectedly large number of genes were synergistically or antagonistically regulated by oxygen and Zn availability. This combinatorial regulation suggested a more prominent involvement of Zn in mitochondrial biogenesis and function than hitherto identified.

Published ahead of print on 12 October 2007.

Supplemental material for this article may be found at http://aem.asm.org/.

Both authors contributed equally to this work.

Present address: DSM Nutritional Products AG, Center of Biotechnology, Basel CH-4002, Switzerland.