Lysine is an inexpensive, abundantly available smart donor in transaminase-catalyzed reactions that can be leveraged for the synthesis of chiral amines using wild-type enzymes. We have shown its utility across an array of transaminases and demonstrated mechanistic evidence for its impact on the reaction equilibrium. Using lysine as an amine donor, we prepared previously inaccessible ncAAs, including derivatives of phenylalanine, tyrosine, and tryptophan, with generally high yields and excellent selectivities. Furthermore, we demonstrated the scalability and practicality of this method by conducting the reaction on large scale to give stereochemically pure product under mild, environmentally friendly conditions.