3-(Aminomethyl) pyridine (3-AMP) is a versatile compound for the synthesis of pharmaceuticals, agricultural chemicals and numerous polymers. Efficient and mild biocatalytic synthesis is often an excellent supplement to traditional chemical synthesis methods. However, there has been no report of biocatalytic 3-AMP synthesis. In this paper, 3-AMP was synthesized for the first time by using biocatalysts co-expressing carboxylic acid reductase from Neurospora crassa (ncCAR) and ω-transaminase from Ochrobactrum anthropi (OATA) in one pot. In addition, the metabolic pathway was optimized by knocking out the transcriptional dual regulator arcA, which resulted in a 90% increase in the yield of 3-AMP. Furthermore, efficient self-sufficient whole-cell bioconversion was established by optimization, achieving 93% yield and a 40.6 mM (4.4 g/L) titer of 3-AMP without additional carbon sources. This whole-cell bioconversion system was also suitable for the high-efficiency biocatalytic synthesis of other aromatic or heterocyclic primary amines, such as benzylamine, 2-furfurylamine, 4-fluorobenzylamine, 2,4-difluorobenzylamine and 2-(aminomethyl) pyridine.

Being entirely biocatalytic, our one-pot procedure provides considerable advantages in terms of economic, environmental and safety impacts over reported chemical methods.