Presentation Information
[2BRBP-06]From Lignin to High-Value Natural Products: Biorefinery and Synthetic Biology for Aromatic Compound Valorization
○Daochen Zhu1 (1. Jiangsu University (China))
Keywords:
Lignin biorefinery,Synthetic biology,Aromatic compounds,Green manufacturing,Depolymerization,Bioconversion
Lignin is the largest renewable reservoir of aromatic carbon, yet its structural heterogeneity, recalcitrance, and low product selectivity continue to limit high-value utilization. Here, we present an integrated strategy that combines lignin biorefinery with synthetic biology to convert lignin-derived aromatics into high-value natural products.
Our approach is built on the coupling of extremophilic microbial resources with pathway and process engineering. Efficient lignin-degrading strains were isolated from extreme environments, including South China Sea sediments. Among them, Bacillus ligniniphilus L1 and Pseudomonas sp. Hu109 showed strong aromatic substrate utilization capacity and stress tolerance. Using multi-omics analysis and metabolic network reconstruction, we resolved key lignin conversion routes, particularly the vanillin biosynthetic pathway in B. ligniniphilus L1. These insights were further integrated with pretreatment optimization, chassis engineering, pathway refactoring, enzyme design, spatial assembly, and fermentation scale-up to build complete biosynthetic routes from lignin-derived aromatic intermediates to target products.
As a representative example, elucidation and engineering of the vanillin pathway enabled a 28-fold increase in production, while a fed-batch strategy alleviated product cytotoxicity and improved process stability. In parallel, a rationally designed cyclized laccase with enhanced stability was developed and applied in 3D-printed bio-based materials. Beyond vanillin, we established biosynthetic routes for resveratrol and cardamonin from lignin-derived aromatic precursors using Pseudomonas sp. Hu109, B. ligniniphilus L1, and engineered Escherichia coli as chassis strains. Stable production of resveratrol from p-coumaric acid was validated in 5-L fermenters, while multi-enzyme cascades combined with synthetic membraneless organelle strategies provided an efficient route for cardamonin biosynthesis. These efforts further supported expansion toward additional nutritionally relevant aromatic molecules, including curcumin and sesamin.
Together, this work establishes an integrated feedstock-to-product technology chain spanning lignin pretreatment, aromatic precursor channeling, chassis development, pathway assembly, and scale-up validation. The results highlight a practical route for transforming lignin from a recalcitrant waste stream into a sustainable source of high-value aromatic natural products, and provide a foundation for future industrial implementation of lignin biorefinery.
Our approach is built on the coupling of extremophilic microbial resources with pathway and process engineering. Efficient lignin-degrading strains were isolated from extreme environments, including South China Sea sediments. Among them, Bacillus ligniniphilus L1 and Pseudomonas sp. Hu109 showed strong aromatic substrate utilization capacity and stress tolerance. Using multi-omics analysis and metabolic network reconstruction, we resolved key lignin conversion routes, particularly the vanillin biosynthetic pathway in B. ligniniphilus L1. These insights were further integrated with pretreatment optimization, chassis engineering, pathway refactoring, enzyme design, spatial assembly, and fermentation scale-up to build complete biosynthetic routes from lignin-derived aromatic intermediates to target products.
As a representative example, elucidation and engineering of the vanillin pathway enabled a 28-fold increase in production, while a fed-batch strategy alleviated product cytotoxicity and improved process stability. In parallel, a rationally designed cyclized laccase with enhanced stability was developed and applied in 3D-printed bio-based materials. Beyond vanillin, we established biosynthetic routes for resveratrol and cardamonin from lignin-derived aromatic precursors using Pseudomonas sp. Hu109, B. ligniniphilus L1, and engineered Escherichia coli as chassis strains. Stable production of resveratrol from p-coumaric acid was validated in 5-L fermenters, while multi-enzyme cascades combined with synthetic membraneless organelle strategies provided an efficient route for cardamonin biosynthesis. These efforts further supported expansion toward additional nutritionally relevant aromatic molecules, including curcumin and sesamin.
Together, this work establishes an integrated feedstock-to-product technology chain spanning lignin pretreatment, aromatic precursor channeling, chassis development, pathway assembly, and scale-up validation. The results highlight a practical route for transforming lignin from a recalcitrant waste stream into a sustainable source of high-value aromatic natural products, and provide a foundation for future industrial implementation of lignin biorefinery.
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