Reimagining Lignin Valorization: Synthetic Biology-Enabled Sustainable Aromatic Carbon Biomanufacturing.

Lignin, the largest renewable aromatic carbon reservoir, represents a foundational yet underutilized feedstock for sustainable biomanufacturing. Despite decades of effort, its effective integration remains constrained, not only by inefficient depolymerization but critically by the lack of coordinated control across depolymerization, conversion, and metabolic regulation. Lignin's heterogeneity and dynamic derivative evolution undermine conventional pathway-centric engineering, causing poor predictability and flux imbalances. This review proposes a paradigm shift from isolated catalytic steps toward an integrated depolymerization, conversion, and regulation framework, where synthetic biology provides the design logic to sense and manage lignin-derived chemical complexity. Emerging technologies like photo-enzymatic catalysis and chemo-biological hybrids expand the design space for selective depolymerization. At the cellular level, microbial cell factories funnel heterogeneous aromatics into defined metabolic nodes. Crucially, these developments converge on a central insight: regulatory control, rather than pathway completeness alone, governs the efficiency, robustness, and scalability of lignin bioconversion. Global transcriptional regulation, dynamic biosensor-based control, and growth-production decoupling establish systems-level governance over carbon flux. By integrating dynamic regulation with modular pathways, lignin is transformed from an unpredictable substrate into a programmable aromatic feedstock. This work outlines a roadmap for lignin valorization, positioning synthetic biology-enabled regulation as the unifying principle for sustainable aromatic carbon biomanufacturing.