E. coli metabolic engineering for gram scale production of a plant-based anti-inflammatory agent

In this report, the heterologous production of salicylate (SA) is the basis for metabolic extension to salicylate 2-O-β-d-glucoside (SAG), a natural product implicated in plant-based defense mechanisms. Production was optimized through a combination of metabolic engineering, gene expression variation, and co-culture design. When combined, SA and SAG production titers reached ~0.9 g/L and ~2.5 g/L, respectively. The SAG compound was then tested for anti-inflammatory properties relative to SA and acetylsalicylate (aspirin). Results indicate comparable activity between SAG and aspirin in reducing nitric oxide (NO) and reactive oxygen species (ROS) from macrophage cells while no discernable negative effects on cellular viability were observed.