Biological funneling of depolymerized lignin streams: toward the integration of chemical depolymerization and microbial conversion

Abstract Lignin is the most abundant natural aromatic polymer on Earth, and its conversion into value-added chemicals has attracted considerable interest as a sustainable alternative to petroleum-derived aromatics. Coupling chemical depolymerization with microbial catabolic pathways has emerged as a promising strategy for lignin valorization by converting heterogeneous lignin-derived aromatics into common metabolic intermediates that can be redirected toward diverse products. Although substantial progress has been achieved using model compounds and simplified substrates, studies employing depolymerized lignin streams derived from lignocellulosic biomass remain limited because their aromatic composition varies considerably depending on the lignin source and depolymerization strategy. Moreover, differences in microbial substrate utilization and the limited substrate range of current production hosts further restrict the efficient conversion of depolymerized lignin streams. This review summarizes recent advances in the biological production of value-added chemicals from lignin-derived aromatics, with particular emphasis on the relationship between chemical depolymerization strategies, the composition of depolymerized lignin streams, and biological funneling toward value-added chemicals. We further discuss emerging strategies for expanding microbial substrate utilization and designing depolymerized lignin streams compatible with microbial conversion, highlighting the co-design of chemical depolymerization and microbial conversion as a key direction toward sustainable lignin valorization and lignin-based biorefineries.