Chemico-biological cascade catalysis of fructose into 2,5-bis(hydroxymethyl)furan in aqueous solution of polyethylene glycol-1000.

Chemico-biological cascade catalysis of hexose into 2,5-bis(hydroxymethyl)furan (BHMF) is desirable but limited by the incompatibility between the solvent and whole-cell catalyst. In this work, aqueous polyethylene glycol (PEG-1000) solution was proven to facilitate both chemical dehydration of fructose and bioreduction of 5-hydroxymethylfurfural (HMF). A high HMF yield of 0.80 was obtained from fructose using 50 mol% HCl in 60 wt% PEG-1000, in which PEG-1000 significantly restrained the formation of by-products. Nuclear magnetic resonance (NMR) analysis revealed that PEG formed hydrogen bonds with HMF and disrupted the original water-water hydrogen bond network. Such dual regulatory effects restricted the nucleophilic attack of water molecules, thereby efficiently inhibiting HMF rehydration. On the other hand, PEG-1000 was biocompatible to E. cloacae HA188, which retained 91% relative activity when it was exposed to 15 wt% PEG-1000 solution, thus the diluted crude HMF was reduced to BHMF at 0.89 yield by E. cloacae HA188 at 35℃. Finally, 454 mM of fructose was converted to BHMF with an overall yield of 0.71 by a tandem chemobiocatalytic approach under mild conditions, providing a sustainable strategy for the production of valuable furan-based chemicals.