State-of-the-art lignin depolymerization and its routes to microbial valorization.

Lignin, a major constituent of lignocellulosic biomass, represents an abundant yet underexploited renewable aromatic reservoir. Unlocking its value requires not only efficient depolymerization but also a clear understanding of how depolymerization routes interface with downstream bioconversion, which is a conceptual shift toward integrated depolymerization-to-valorization design. This review systematically evaluates state-of-the-art strategies for lignin depolymerization. Physical methods improve accessibility and structural disruption but often achieve effective bond cleavage only when coupled with other methods. Chemical depolymerization, encompassing catalytic, oxidative, reductive, and solvolytic routes, enables targeted cleavage of key inter-unit lignin linkages such as β-O-4, β-β, and β-5 to generate phenolic monomers and oligomers. Biological depolymerization harnesses enzymes and microorganisms to achieve selective lignin modification under mild conditions, though challenges remain in reaction rates, substrate heterogeneity, and scalability. Beyond depolymerization, this review highlights the microbial upgrading of lignin-derived aromatics into value-added products through pathway engineering, synthetic biology, and systems metabolic engineering. Particular emphasis is placed on the construction of robust microbial cell factories capable of improving carbon funneling efficiency and enabling selective product biosynthesis. This transformation links molecular-level depolymerization mechanisms with metabolic pathway design for improved bioconversion efficiency. While individual depolymerization technologies each present unique strengths and limitations, emerging integrated strategies that combine chemical and biological routes with robust microbial valorization offer a promising foundation for cost-effective, scalable, and sustainable lignin biorefineries, supporting the development of a circular bioeconomy.