title: E. coli metabolic engineering for gram scale production of a plant-based anti-inflammatory agent.
abstract: 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 ~0.9g/L and ~2.5g/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.
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo NY 14260, USA.
authors.forename: Mahmoud Kamal
authors.initials: MK
authors.lastname: Ahmadi
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo NY 14260, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo NY 14260, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Moscatello
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo NY 14260, USA. Electronic address: blainepf@buffalo.edu.
authors.forename: Blaine A
authors.initials: BA
authors.lastname: Pfeifer
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification / Q000378:metabolism*; D017360:Arabidopsis / Q000502:physiology*; D053898:Biosynthetic Pathways / Q000235:genetics; D004926:Escherichia coli / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000235:genetics; D024861:Genetic Enhancement / Q000379:methods; D060847:Metabolic Engineering / Q000379:methods*; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020156:Salicylic Acid / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D029968:Escherichia coli Proteins; D011994:Recombinant Proteins; D020156:Salicylic Acid
keywords: Anti-inflammatory; Co-culture; E. coli; Plant; Salicylate; Salicylate 2-O-β-D-glucoside