Palladium nanocatalyst assisted in situ regeneration of amino donor in a one-enzyme cascade†

α-Chiral amines are key intermediates for scalable preparation of bioactive compounds; herein we present a novel palladium-based nanocatalyst capable of selectively catalyzing the reductive amination of carbonyl compounds, which enables the in situ regeneration of amino donors from wasteful co-products in a one-enzyme cascade using ω-transaminase, without the requirement of the expensive coenzyme NAD(P)H. The cascade network combines a ω-transaminase-assisted transamination with a selective reductive amination reaction facilitated by a heterogeneous palladium-based nanocatalyst. Nitrogen is sourced from hydroxylamine ions to convert generated co-products back into amino donors, yielding chiral amines with exceptional yields of up to 99% and excellent enantioselectivity. This chemoenzymatic one-enzyme transamination-reductive amination cascade network is highly atom-efficient and generates H₂O as its sole by-product, demonstrating its potential impact in synthetic chemistry and beyond.