Abstract
Lignin, a natural and renewable aromatic polymer, serves as a plentiful source of aromatic building blocks for biomanufacturing. However, despite its potential, the bioconversion efficiency of lignin remains limited due to its inherently complex structure and the constraints of traditional metabolic engineering approaches. Synthetic biology-guided metabolic regulation offers a solution by coordinating intracellular resource allocation in ligninolytic strains, endowing their adaptation for industrial applications and promoting the sustainability of lignin-based bioeconomy. This review provides a comprehensive overview of multiscale metabolic regulation, including critical enzymes involved in biotransformation, metabolic pathway networks, genome-phenotype, and learning prediction. It highlights the significant roles and potential benefits of emerging cutting-edge technologies in advancing lignin valorization. Overall, synthetic biology-guided metabolic regulation has demonstrated its power in balancing the metabolic fluxes of ligninolytic strains, ensuring the continued vitality in future development.