Discovery and Functional Characterization of a Yeast Sugar Alcohol Phosphatase

Yi Fan Xu, Wenyun Lu, Jonathan C. Chen, Sarah A. Johnson, Patrick A. Gibney, David G. Thomas, Greg Brown, Amanda L. May, Shawn R. Campagna, Alexander F. Yakunin, David Botstein, Joshua D. Rabinowitz

Research output: Contribution to journalArticle

Abstract

Sugar alcohols (polyols) exist widely in nature. While some specific sugar alcohol phosphatases are known, there is no known phosphatase for some important sugar alcohols (e.g., sorbitol-6-phosphate). Using liquid chromatography-mass spectrometry-based metabolomics, we screened yeast strains with putative phosphatases of unknown function deleted. We show that the yeast gene YNL010W, which has close homologues in all fungi species and some plants, encodes a sugar alcohol phosphatase. We term this enzyme, which hydrolyzes sorbitol-6-phosphate, ribitol-5-phosphate, and (d)-glycerol-3-phosphate, polyol phosphatase 1 or PYP1. Polyol phosphates are structural analogs of the enediol intermediate of phosphoglucose isomerase (Pgi). We find that sorbitol-6-phosphate and ribitol-5-phosphate inhibit Pgi and that Pyp1 activity is important for yeast to maintain Pgi activity in the presence of environmental sugar alcohols. Pyp1 expression is strongly positively correlated with yeast growth rate, presumably because faster growth requires greater glycolytic and accordingly Pgi flux. Thus, yeast express the previously uncharacterized enzyme Pyp1 to prevent inhibition of glycolysis by sugar alcohol phosphates. Pyp1 may be useful for engineering sugar alcohol production.

Original languageEnglish (US)
Pages (from-to)3011-3020
Number of pages10
JournalACS chemical biology
Volume13
Issue number10
DOIs
StatePublished - Oct 19 2018

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine

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    Xu, Y. F., Lu, W., Chen, J. C., Johnson, S. A., Gibney, P. A., Thomas, D. G., Brown, G., May, A. L., Campagna, S. R., Yakunin, A. F., Botstein, D., & Rabinowitz, J. D. (2018). Discovery and Functional Characterization of a Yeast Sugar Alcohol Phosphatase. ACS chemical biology, 13(10), 3011-3020. https://doi.org/10.1021/acschembio.8b00804