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Open Access Research article

The impact of oxygen on the transcriptome of recombinant S. cerevisiae and P. pastoris - a comparative analysis

Kristin Baumann1, Laura Dato2, Alexandra B Graf34, Gianni Frascotti2, Martin Dragosits36, Danilo Porro2, Diethard Mattanovich35, Pau Ferrer1* and Paola Branduardi2

Author Affiliations

1 Department of Chemical Engineering, Autonomous University of Barcelona, Spain

2 Department of Biotechnology and Bioscience, University of Milano-Bicocca, Milan, Italy

3 Institute of Applied Microbiology, Department of Biotechnology, University of Natural Resources and Applied Life Sciences, Vienna, Austria

4 School of Bioengineering, University of Applied Sciences, FH Campus Vienna, Austria

5 Austrian Centre of Industrial Biotechnology (ACIB GmbH), Vienna, Austria

6 Department of Computer Science, UC Davis Genome Center, University of California, Davis, USA

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BMC Genomics 2011, 12:218  doi:10.1186/1471-2164-12-218

Published: 9 May 2011

Abstract

Background

Saccharomyces cerevisiae and Pichia pastoris are two of the most relevant microbial eukaryotic platforms for the production of recombinant proteins. Their known genome sequences enabled several transcriptomic profiling studies under many different environmental conditions, thus mimicking not only perturbations and adaptations which occur in their natural surroundings, but also in industrial processes. Notably, the majority of such transcriptome analyses were performed using non-engineered strains.

In this comparative study, the gene expression profiles of S. cerevisiae and P. pastoris, a Crabtree positive and Crabtree negative yeast, respectively, were analyzed for three different oxygenation conditions (normoxic, oxygen-limited and hypoxic) under recombinant protein producing conditions in chemostat cultivations.

Results

The major differences in the transcriptomes of S. cerevisiae and P. pastoris were observed between hypoxic and normoxic conditions, where the availability of oxygen strongly affected ergosterol biosynthesis, central carbon metabolism and stress responses, particularly the unfolded protein response. Steady state conditions under low oxygen set-points seemed to perturb the transcriptome of S. cerevisiae to a much lesser extent than the one of P. pastoris, reflecting the major tolerance of the baker's yeast towards oxygen limitation, and a higher fermentative capacity. Further important differences were related to Fab production, which was not significantly affected by oxygen availability in S. cerevisiae, while a clear productivity increase had been previously reported for hypoxically grown P. pastoris.

Conclusions

The effect of three different levels of oxygen availability on the physiology of P. pastoris and S. cerevisiae revealed a very distinct remodelling of the transcriptional program, leading to novel insights into the different adaptive responses of Crabtree negative and positive yeasts to oxygen availability. Moreover, the application of such comparative genomic studies to recombinant hosts grown in different environments might lead to the identification of key factors for efficient protein production.