Whole-Cell Biosynthesis of 2,5-Furandicarboxylic Acid for Sustainable Manufacturing: Prospects and Challenges

2,5-Furandicarboxylic acid (FDCA) has emerged as a promising sustainable alternative to petroleum-derived terephthalic acid for the production of biobased polymers such as polyethylene furanoate (PEF). Various catalytic methods, including chemocatalysis, biocatalysis, photocatalysis, and electrocatalysis, have been developed for FDCA synthesis. Among these, biocatalysis stands out as a green and efficient strategy due to its mild reaction conditions, low cost, high selectivity, and environmental compatibility. Whole-cell biocatalysis, in particular, eliminates the need for enzyme purification and external cofactor regeneration by using living microbial cells as integrated factories to perform multistep reactions under mild conditions with high efficiency and cost-effectiveness. This review summarizes recent advances in the whole-cell biocatalytic synthesis of FDCA from two key platform molecules─5-hydroxymethylfurfural (HMF) and furfural (FFA). It highlights the design principles, performance, and limitations of various catalytic systems developed to date. Despite considerable progress, several challenges remain, including limited substrate tolerance, inefficient cofactor regeneration, narrow pathway diversity, and uncertain techno-economic feasibility.