Microbial valorization of lignin toward coumarins: Challenges and perspectives

Lignin is the largest renewable aromatic resource in nature, while aromatic natural products, coumarins, are part of a large family of plant secondary metabolites with many pharmacological activities. One of the key advantages of lignin is its rich reservoir of aromatic building blocks, making it an ideal source for potential precursors in the biosynthesis of coumarins. The bioconversion of lignin to coumarin aligns with the principles of a sustainable bioeconomy, but this conversion has not been fully realized due to the limited availability of lignin derivatives and the unsatisfactory biosynthesis performance of coumarins. This work thus prospects a promising atom-economic route of microbial synthesis of coumarins from lignin derivatives, advancing both lignin bio-upgrading and coumarin production. The biosynthesis pathways of coumarins and key enzymes are first summarized to facilitate the construction of a microbial cell factory. Various fractionation technologies can be employed to enhance the availability of lignin derivatives by effectively yielding a greater number of potential precursors for the synthesis of coumarins. Identifying the crossover nodes and key aromatic intermediates enabled the microbial synthesis of coumarins and lignin bioconversion. Promising engineering strategies could further promote the microbial synthesis of aromatic natural products. Overall, bridging the microbial synthesis of coumarins with the bioconversion of lignin will facilitate the practical valorization of lignin and promote sustainable coumarin production.