Multiscale metabolic engineering in biological lignin valorization

Public summary

* Multiscale metabolic engineering injects strong vigor into biological lignin valorization.

* Cutting-edge technologies in synthetic biology bring lignin bio-upgrading to an era of flexible regulation.

* Efforts are still needed to mine biological information and promote multidisciplinary integration.

* The convergence of synthetic biology with artificial intelligence will be the future trajectory.

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.