Microbial Lignin Valorization to Protocatechuic Acid and Catechol: Biofunneling Pathways and Metabolic Engineering Strategies.

Lignin, an abundant and renewable aromatic biopolymer, represents a largely underutilized resource for the sustainable production of high-value chemicals. Among lignin-derived intermediates, protocatechuic acid (PCA) and catechol have emerged as key platform molecules due to their versatile applications in pharmaceuticals, polymers, and fine chemicals. This review provides a critical overview of microbial lignin valorization focusing on the microbial conversion of lignin-derived aromatics into PCA and catechol. It highlights recent advances in lignin depolymerization techniques, including thermochemical and biological approaches, and examines their influence on the generation of bioavailable aromatic feedstocks. We systematically discuss microbial biofunneling pathways that converge diverse lignin-derived compounds into PCA and catechol, emphasizing the role of central metabolic nodes and enzymatic transformations such as O-demethylation, hydroxylation, and decarboxylation. We treat protocatechuate decarboxylase (PCADC) as the central enzymatic bridge linking PCA and catechol. However, it should be noted that many reported microbial production strategies have been demonstrated using purified lignin-derived aromatic model compounds (e.g., ferulate, vanillate,