Asymmetric reductive amination by a wild-type amine dehydrogenase from the thermophilic bacteria Petrotoga mobilisC. V.-V. and A. Z. designed and supervised this study. O. M. and S. D. conducted the biocatalysis work. E. D. performed the MS analyses. C. V.-V., A. Z., O. M., S. D. and V. D. B. wrote the manuscript. M. S. contributed to the design of this study. J.-L. P., V. P., A. D. and A. M. performed the steps required for protein production and purification. C. V.-V. and V. D. B. supervised the experiments.Electronic supplementary information (ESI) available: Protein gels, HPLC chromatogram, NMR analyses. See DOI: 10.1039/c6cy01625a

The biocatalytic reductive amination of ketone to chiral amine is one of the most challenging reactions. Using a genome-mining approach, we found proteins catalyzing the reductive amination of ketones without a carboxylic function in the α or β position. The synthesis of (4S)-4-aminopentanoic acid (ee ≥99.5%) was achieved with the thermoactive amine dehydrogenase (AmDH) AmDH4 from Petrotoga mobilisin 88% yield. The high stability and substrate tolerance make AmDH4 a very good starting point for further discovery of reductive amination biocatalysts with an enlarged substrate range. This is the first report of wild-type enzymes with related genes having proper NAD(P)H–AmDH activity.