Conversion of cysteine to 3-mercaptopyruvic acid by bacterial aminotransferases

Enzyme Microb Technol. 2017 Apr:99:38-48. doi: 10.1016/j.enzmictec.2017.01.004. Epub 2017 Jan 16.

Abstract

3-Mercaptopyruvate (3MPy), a structural analog of 3-mercaptopropionic acid, is a precursor compound for biosynthesis of polythioesters in bacteria. The cost-effectiveness and sustainability of the whole process could be greatly improved by using the cysteine degradation pathway for an intracellular supply of 3MPy. Transamination of cysteine to its corresponding α-keto acid 3MPy is catalyzed by cysteine aminotransferases (CAT). However, CAT activity has so far not been described for bacterial aminotransferases (AT), and it was unknown whether they can be applied for the conversion of cysteine to 3MPy. In this study, we selected eight bacterial aminotransferases based on sequence homology to CAT of Rattus norvegicus (Got1). The aminotransferases included four aspartate aminotransferases (AATs) and four aromatic amino acid aminotransferases (ArATs) from Advenella mimigardefordensis DPN7, Escherichia coli MG1655, Shimwellia blattae ATCC 33430, Ralstonia eutropha H16 and Paracoccus denitrificans PD1222. For a more detailed characterization, all selected AAT or ArAT encoding genes were heterologously expressed in E. coli and purified. CAT activity was detected for all aminotransferases when a novel continuous coupled enzyme assay was applied. Kinetic studies revealed the highest catalytic efficiency of 5.1mM/s for AAT from A. mimigardefordensis. Formation of 3MPy from cysteine could additionally be verified by an optimized approach using derivatization of 3MPy with the Girard T reagent and liquid chromatography-mass spectrometry analyses.

Keywords: 3-mercaptopyruvate; Aminotransferase; Aspartate; Cysteine; Polythioester.

MeSH terms

  • Alcaligenaceae / enzymology
  • Alcaligenaceae / genetics
  • Amino Acid Sequence
  • Aspartate Aminotransferases / genetics
  • Aspartate Aminotransferases / metabolism
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cupriavidus necator / enzymology
  • Cupriavidus necator / genetics
  • Cysteine / analogs & derivatives*
  • Cysteine / biosynthesis
  • Cysteine / metabolism*
  • Enterobacteriaceae / enzymology
  • Enterobacteriaceae / genetics
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Genes, Bacterial
  • Industrial Microbiology
  • Kinetics
  • Paracoccus denitrificans / enzymology
  • Paracoccus denitrificans / genetics
  • Phylogeny
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Transaminases / genetics
  • Transaminases / metabolism*

Substances

  • Bacterial Proteins
  • Recombinant Proteins
  • 3-mercaptopyruvic acid
  • Transaminases
  • Aspartate Aminotransferases
  • cysteine aminotransferase
  • aromatic amino acid aminotransferase
  • Cysteine