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Applied Microbiology and Biotechnology

, Volume 102, Issue 2, pp 723–732 | Cite as

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

  • Miyu Nishikawa
  • Yuuka Masuyama
  • Motomichi Nunome
  • Kaori Yasuda
  • Toshiyuki Sakaki
  • Shinichi Ikushiro
Biotechnologically relevant enzymes and proteins

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.

Keywords

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

Notes

Acknowledgements

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

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

253_2017_8621_MOESM1_ESM.pdf (556 kb)
ESM 1 (PDF 555kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Miyu Nishikawa
    • 1
    • 2
  • Yuuka Masuyama
    • 2
  • Motomichi Nunome
    • 2
  • Kaori Yasuda
    • 2
  • Toshiyuki Sakaki
    • 2
  • Shinichi Ikushiro
    • 2
  1. 1.Imizu Research Center, TOPUBIO Research Co., Ltd.ToyamaJapan
  2. 2.Department of Biotechnology, Faculty of EngineeringToyama Prefectural UniversityToyamaJapan

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