Sterol 3β-glucosyltransferase biocatalysts with a range of selectivities, including selectivity for testosterone

Mol Biosyst. 2013 Nov;9(11):2816-22. doi: 10.1039/c3mb70303g.

Abstract

The main objectives of this work were to characterise a range of purified recombinant sterol 3β-glucosyltransferases and show that rational sampling of the diversity that exists within sterol 3β-glucosyltransferase sequence space can result in a range of enzyme selectivities. In our study the catalytically active domain of the Saccharomyces cerevisiae 3β-glucosyltransferase was used to mine putative sterol 3β-glucosyltransferases from the databases. Selected diverse sequences were expressed in and purified from Escherichia coli and shown to have different selectivities for the 3β-hydroxysteroids ergosterol and cholesterol. Surprisingly, three enzymes were also selective for testosterone, a 17β-hydroxysteroid. This study therefore reports for the first time sterol 3β-glucosyltransferases with selectivity for both 3β- and 17β-hydroxysteroids and is also the first report of recombinant 3β-glucosyltransferases with selectivity for steroids with a hydroxyl group at positions other than C-3. These enzymes could therefore find utility in the pharmaceutical industry for the green synthesis of a range of glycosylated compounds of medicinal interest.

MeSH terms

  • Amino Acid Sequence
  • Catalysis
  • Catalytic Domain
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Glucosyltransferases / chemistry
  • Glucosyltransferases / genetics
  • Glucosyltransferases / metabolism*
  • Kinetics
  • Molecular Sequence Data
  • Protein Interaction Domains and Motifs
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Sequence Alignment
  • Sterols / metabolism*
  • Substrate Specificity
  • Testosterone / metabolism*

Substances

  • Sterols
  • Testosterone
  • Glucosyltransferases