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Whole-cell-dependent biosynthesis of sulfo-conjugate using human sulfotransferase expressing budding yeast

Abstract

Cytosolic sulfotransferases (SULTs), one of the predominant phase II drug metabolizing enzymes (DME), play important roles in metabolism of xeno- and endobiotics to generate their sulfo-conjugates. These sulfo-conjugates often have biological activities but are difficult to study, because even though only small amounts are required to evaluate their efficacy and safety, chemical or biological synthesis of sulfo-conjugatesis is often challenging. Previously, we constructed a DME expression system for cytochrome P450 and UGT, using yeast cells, and successfully produced xenobiotic metabolites in a whole-cell-dependent manner. In this study, we developed a yeast expression system for human SULTs, including SULT1A1, 1A3, 1B1, 1C4, 1E1, and 2A1, in Saccharomyces cerevisiae and examined its sulfo-conjugate productivity. The recombinant yeast cells expressing each of the SULTs successfully produced several hundred milligram per liter of xeno- or endobioticsulfo-conjugates within 6 h. This whole-cell-dependent biosynthesis enabled us to produce sulfo-conjugates without the use of 3’-phosphoadenosine-5’-phosphosulfate, an expensive cofactor. Additionally, the production of regiospecific sulfo-conjugates of several polyphenols was possible with this method, making this novel yeast expression system a powerful tool for uncovering the metabolic pathways and biological actions of sulfo-conjugates.

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Acknowledgements

The study was supported by the JSPSKAKENHI Grant Number JP26292072(SI).

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Correspondence to Shinichi Ikushiro.

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Nishikawa, M., Masuyama, Y., Nunome, M. et al. Whole-cell-dependent biosynthesis of sulfo-conjugate using human sulfotransferase expressing budding yeast. Appl Microbiol Biotechnol 102, 723–732 (2018). https://doi.org/10.1007/s00253-017-8621-x

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  • DOI: https://doi.org/10.1007/s00253-017-8621-x

Keywords

  • Sulfotransferase (SULT)
  • Sulfo-conjugate
  • Regioselective biosynthesis
  • Heterologous expression system in yeast
  • Xenobiotic metabolism