Biocatalytic Valorization of Biobased 5-Hydroxymethylfurfural to 5-Hydroxymethyl-2-furfurylamine in a Three-Constituent Deep Eutectic Solvent–Water System

5-Hydroxymethyl-2-furfurylamine (HMFA), as an important 5-hydroxymethylfurfural (5-HMF) derivative, has many potential applications in the preparation of diuretics, antihypertensive drugs, preservatives, and curing agents. In this work, highly efficient valorization of biomass-derived d-fructose into HMFA was attempted via a cascade reaction in a three-constituent deep eutectic solvent (3c-DES)–H2O. Using d-fructose (63.0 g/L) as a raw material, the yield of 5-HMF reached 68.2% in 3c-DES malic acid/glycerol/betaine–H2O (9:91, wt/wt) (pH 2.3) at 170 °C in 30 min. Whole cells of Escherichia coli CV harboring transaminase were utilized to valorize biomass-derived 5-HMF to HMFA at pH 8.0 and 30 °C using amine donor l-alanine. The valorization of 600 mM commercial 5-HMF gave a 93.2% yield of HMFA with 99.2% selectivity. In addition, CV cells transformed d-fructose-valorized 5-HMF into HMFA in 94.1% yield in 3c-DES malic acid/glycerol/betaine–H2O. This approach provided a sustainable and eco-efficient idea for chemoenzymatically valorizing biomass-derived d-fructose to HMFA.