Genome scale reconstruction of lignin-derived aromatic catabolism across Pseudomonas enables modular chassis design for lignin bioconversion

Abstract

Pseudomonas is a metabolically versatile genus that has emerged as a promising chassis for upgrading lignin-derived aromatics, yet current knowledge remains fragmented across individual strains and pathways. Here, we synthesize genus-scale evidence to reframe lignin valorization in Pseudomonas as a modular catabolic architecture in which diverse peripheral “entry” routes converge on a small set of conserved central funnels. We compiled canonical gene sets for nine lignin-derived aromatic catabolic routes and performed a genome-guided survey across 365 publicly available Pseudomonas genomes, enabling a comparative map of pathway distribution and co-occurrence. To make the analysis reusable, we operationalized each route as an essential gene module and constructed a genome-by-module completeness matrix. This matrix reveals genome-wide representation of all nine routes and identifies six additional Pseudomonas taxa encoding near complete lignin aromatic pathways, thereby expanding the pool of candidate chassis for downstream validation and engineering. Building on this modular view, we summarize system and synthetic biology strategies spanning pathway rewiring, tolerance engineering, regulatory tuning, and CRISPR enabled genome editing to translate genomic potential into scalable bioprocess performance and product formation. Collectively, this review provides a design-oriented framework to prioritize Pseudomonas chassis and assemble pathway modules for lignin to chemical bioconversion.