Expanding the Toolbox of R-Selective Amine Transaminases by Identification and Characterization of New Members

Aline Telzerow, Juraj Paris, Maria Håkansson, Javier González-Sabín, Nicolas Ríos-Lombardía, Harald Gröger, Francisco Morís, Martin Schürmann, Helmut Schwab*, Kerstin Steiner*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Amine transaminases (ATAs) are used to synthesize enantiomerically pure amines, which are building blocks for pharmaceuticals and agrochemicals. R-selective ATAs belong to the fold type IV PLP-dependent enzymes, and different sequence-, structure- and substrate scope-based features have been identified in the past decade. However, our knowledge is still restricted due to the limited number of characterized (R)-ATAs, with additional bias towards fungal origin. We aimed to expand the toolbox of (R)-ATAs and contribute to the understanding of this enzyme subfamily. We identified and characterized four new (R)-ATAs. The ATA from Exophiala sideris contains a motif characteristic for d-ATAs, which was previously believed to be a disqualifying factor for (R)-ATA activity. The crystal structure of the ATA from Shinella is the first from a Gram-negative bacterium. The ATAs from Pseudonocardia acaciae and Tetrasphaera japonica are the first characterized (R)-ATAs with a shortened/missing N-terminal helix. The active-site charges vary significantly between the new and known ATAs, correlating with their diverging substrate scope.

Original languageEnglish
Pages (from-to)1232-1242
Number of pages11
JournalChemBioChem
Volume22
Issue number7
Early online date26 Nov 2020
DOIs
Publication statusPublished - 6 Apr 2021

Keywords

  • amine transaminases
  • chiral amines
  • fold type IV
  • PLP-dependent enzymes
  • transferases

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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