Sustainable Synthesis of Furfurylamine and Its Derivative N -(Furan-2-ylmethyl)acetamide through Hybrid Biocatalysis

In recent years, with the development of protein engineering and synthetic biology, biocatalytic systems have gradually evolved from single-enzyme reactions to multi-enzyme synergistic whole-cell catalysis. In this study, a dual-cycle regeneration system for amine donor and cofactor recycling was established by coupling a recombinant Alr-FDH system with the HN-AlaDH whole-cell catalytic system, comprising mutant ω-transaminase (HN, His210Asn) derived from Aspergillus terreus and L-alanine dehydrogenase (AlaDH). The resulting dual-bacteria system enabled efficient amination of furfural (FAL) while significantly reducing amine donor consumption. Under optimized fed-batch conditions, 300 mM FAL was converted within 4 h, affording a furfurylamine (FLA) yield of 95.8%. To further increase product value, lipase CALB was employed to catalyze the amidation of FLA using ethyl acetate as the acyl donor. At a lipase loading of 30 U/mL, N-(furan-2-ylmethyl)acetamide (FYA) was obtained in 91.4% yield at an FLA concentration of 3000 mM. Furthermore, a chemobiological catalysis was developed by integrating D-xylose dehydration in a ChCl/MA/MaA-H2O deep eutectic solvent system with whole-cell amination and lipase-catalyzed amidation, enabling the efficient conversion of biomass-derived D-xylose into FYA. Through this cascade, D-xylose was converted into FYA with a yield of 0.32 g FYA/g D-xylose. Overall, this work provides an efficient and sustainable strategy for the valorization of biomass-derived furfural into value-added FLA derivatives.