Revolutionizing lignin valorization: Key advances in demethylation, methylation, and methyl metabolism.

The biological valorization of lignin offers significant potential for the production of valuable bio-based products, addressing the challenges posed by the recalcitrant and heterogeneous of lignin. However, the varying degrees of methoxylation in the three typical lignin units represent a key rate-limiting factor for the efficient biological conversion of lignin derivatives. Herein, this review systematically prospects the processes of demethylation, methylation and methyl metabolism in biological lignin valorization. The demethylases, methyltransferases and enzymatic mechanisms associated with the aromatic catabolism of lignin derivatives had been elaborated in detail. Furthermore, a promising methyl-cycle route for microbial lignin valorization was summarized, enhancing the carbon utilization efficiency in lignin valorization and facilitating the production of natural aromatics. Novel and advanced strategies, including machine learning-assisted enzyme engineering, synthetic biology, and metabolic engineering, are highlighted as transformative tools for overcoming bottlenecks in microbial lignin bioconversion into high-value products. Overall, prospecting demethylation, methylation and methyl metabolism contribute to the sustainable valorization of lignin, fostering the growth of the lignin-based bioeconomy.