A straightforward chemobiocatalytic route for one-pot valorization of glucose into 2,5-bis(hydroxymethyl)furan

Direct conversion of inexpensive biomass into value-added chemicals via furanic platform molecules is highly attractive. In this work, we present a straightforward chemobiocatalytic route for glucose valorization into 2,5-bis(hydroxymethyl)furan (BHMF) in one pot, with no purification of the intermediate 5-hydroxymethylfurfural (HMF). Six candidate alcohol dehydrogenase (ADH) genes were located from Meyerozyma guilliermondii SC1103, based on comparative transcriptome analysis and real-time quantitative polymerase chain reaction. An ADH (MgADH1) was identified upon evaluation of catalytic performances of recombinant Saccharomyces cerevisiae harboring candidate ADHs in HMF reduction. Soluble expression of the enzyme in S. cerevisiae was greatly enhanced by its codon optimization, leading to improved HMF tolerance (up to 400 mM). In a fed-batch process, the desired product of approximately 473 mM (60.5 g/L) was produced within 30 h by recombinant S. cerevisiae_MgADH1. A chemobiocatalytic route toward BHMF was constructed by merging CaCl₂-mediated isomerization and dehydration with biocatalytic reduction with an overall yield of approximately 42%, starting from glucose. This work may pave the way for green manufacture of valuable biobased chemicals.