TY - JOUR
T1 - Expanding the Toolbox of R-Selective Amine Transaminases by Identification and Characterization of New Members
AU - Telzerow, Aline
AU - Paris, Juraj
AU - Håkansson, Maria
AU - González-Sabín, Javier
AU - Ríos-Lombardía, Nicolas
AU - Gröger, Harald
AU - Morís, Francisco
AU - Schürmann, Martin
AU - Schwab, Helmut
AU - Steiner, Kerstin
PY - 2021/4/6
Y1 - 2021/4/6
N2 - 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.
AB - 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.
KW - amine transaminases
KW - chiral amines
KW - fold type IV
KW - PLP-dependent enzymes
KW - transferases
UR - http://www.scopus.com/inward/record.url?scp=85098138433&partnerID=8YFLogxK
U2 - 10.1002/cbic.202000692
DO - 10.1002/cbic.202000692
M3 - Article
C2 - 33242357
AN - SCOPUS:85098138433
SN - 1439-4227
VL - 22
SP - 1232
EP - 1242
JO - ChemBioChem
JF - ChemBioChem
IS - 7
ER -