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Integrated analysis of transcriptome and lipid profiling reveals the co-influences of inositol–choline and Snf1 in controlling lipid biosynthesis in yeast

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Abstract

In the yeast Saccharomyces cerevisiae many genes involved in lipid biosynthesis are transcriptionally controlled by inositol–choline and the protein kinase Snf1. Here we undertook a global study on how inositol–choline and Snf1 interact in controlling lipid metabolism in yeast. Using both a reference strain (CEN.PK113-7D) and a snf1Δ strain cultured at different nutrient limitations (carbon and nitrogen), at a fixed specific growth rate of 0.1 h−1, and at different inositol choline concentrations, we quantified the expression of genes involved in lipid biosynthesis and the fluxes towards the different lipid components. Through integrated analysis of the transcriptome, the lipid profiling and the fluxome, it was possible to obtain a high quality, large-scale dataset that could be used to identify correlations and associations between the different components. At the transcription level, Snf1 and inositol–choline interact either directly through the main phospholipid-involving transcription factors (i.e. Ino2, Ino4, and Opi1) or through other transcription factors e.g. Gis1, Mga2, and Hac1. However, there seems to be flux regulation at the enzyme levels of several lipid involving enzymes. The analysis showed the strength of using both transcriptome and lipid profiling analysis for mapping the co-influence of inositol–choline and Snf1 on phospholipid metabolism.

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Abbreviations

AcCoA:

Acetyl coenzyme A

AceAcCoA:

Acetoacetyl coenzyme A

CDP-DAG:

Cytidine diphosphate-diacylglycerol

Cho:

Choline

DAG:

Diacylglycerol

Etn:

Ethanolamine

ES:

Ergosterol

FA:

Fatty acid or fatty acyl-CoA

Glc-6-P:

Glucose 6-phosphate

G-3-P:

Glycerol 3-phosphate

HIC:

High inositol–choline

IC:

Inositol–choline

LIC:

Low inositol–choline

MaCoA:

Malonyl coenzyme A

PA:

Phosphatidic acids

PC:

Phosphatidylcholine

PE:

Phosphatidylethanolamine

PI:

Phosphatidylinositiol

PL:

Phospholipids

PS:

Phosphatidylserine

Pyr:

Pyruvate

SE:

Sterylester

ST:

Strain factor

TAG:

Triacylglycerol

TF:

Transcription factor

UASINO :

Inositol-sensitive upstream activating sequence

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Acknowledgments

This work was financed by Chalmers Foundation, the Knut and Alice Wallenberg Foundation and the Swedish Research Council (Vetenskapsrådet). We also acknowledge funding from the EU-funded project UNICELLSYS. Pramote Chumnanpuen also would like to thank the Office of the Higher Education Commission, Thailand for support by a stipend for his Ph.D. program under the program Strategic Scholarships for Frontier Research Network. We also thank Nils-Gunnar Carlsson for valuable assistance with running the HPLC-CAD, Tobias Österlund and Klaas Buijs for helpful suggestions on manuscript preparation.

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  1. Systems and Synthetic Biology, Department of Chemical and Biological Engineering, Chalmers University of Technology, Kemivägen 10, 412 96, Gothenburg, Sweden

    Pramote Chumnanpuen, Jie Zhang, Intawat Nookaew & Jens Nielsen

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  1. Pramote Chumnanpuen
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  2. Jie Zhang
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  4. Jens Nielsen
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Correspondence to Jens Nielsen.

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Communicated by S. Hohmann.

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Chumnanpuen, P., Zhang, J., Nookaew, I. et al. Integrated analysis of transcriptome and lipid profiling reveals the co-influences of inositol–choline and Snf1 in controlling lipid biosynthesis in yeast. Mol Genet Genomics 287, 541–554 (2012). https://doi.org/10.1007/s00438-012-0697-5

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