Metal–Organic Frameworks as Synergistic Scaffolds in Biomass Fermentation: Evolution from Passive Adsorption to Active Catalysis

Microbial fermentation stands as the foundational technology in modern biorefineries, yet its industrial scalability is critically constrained by product inhibition, prohibitive downstream separation costs, and substrate inhibition. Metal–organic frameworks (MOFs) offer a tunable material platform to address these challenges through rational design of pore size, shape, and chemical functionality. This review systematically chronicles the evolution of MOF applications in biomass fermentation across four generations, demonstrating a synergistic mapping where the core fermentation challenges—product toxicity, substrate toxicity, and separation energy intensity—align with the inherent MOF advantages of high adsorption capacity, programmable selectivity, and tunable functionality. The applications progress from first-generation passive adsorbents for in situ product removal, to second-generation protective agents for mitigating inhibitors, and third-generation immobilization scaffolds enabling continuous processing. The fourth-generation systems transcend passive scaffolding to position MOFs as active metabolic partners in microbe-MOF hybrids, driving cofactor regeneration and tandem biocatalysis. By synthesizing diverse research streams, ranging from defect engineering to artificial symbiosis, including defect engineering strategies, this review establishes critical design principles for the rational integration of programmable materials in next-generation biorefineries.