title: Microcompartments for B12-dependent 1,2-propanediol degradation provide protection from DNA and cellular damage by a reactive metabolic intermediate.
abstract: Salmonella enterica grows on 1,2-propanediol (1,2-PD) in a coenzyme B(12)-dependent fashion. Prior studies showed that a bacterial microcompartment (MCP) is involved in this process and that an MCP-minus mutant undergoes a 20-h period of growth arrest during 1,2-PD degradation. It was previously proposed that growth arrest resulted from propionaldehyde toxicity, but no direct evidence was presented. Here, high-pressure liquid chromatography analyses of culture medium were used to show that the major products of aerobic 1,2-PD degradation are propionaldehyde, propionate, and 1-propanol. A MCP-minus mutant accumulated a level of propionaldehyde 10-fold higher than that of the wild type (1.6 mM compared to 15.7 mM), associating this compound with growth arrest. The addition of propionaldehyde to cultures of S. enterica caused growth arrest from 8 to 20 mM, but not at 4 mM, providing direct evidence for propionaldehyde toxicity. Studies also indicated that propionaldehyde was toxic due to the inhibition of respiratory processes, and the growth arrest ended when propionaldehyde was depleted primarily by conversion to propionate and 1-propanol and secondarily due to volatility. The Ames test was used to show that propionaldehyde is a mutagen and that mutation frequencies are increased in MCP-minus mutants during 1,2-PD degradation. We propose that a primary function of the MCPs involved in 1,2-PD degradation is the mitigation of toxicity and DNA damage by propionaldehyde.
authors.affiliation: Iowa State University, Department of Biochemistry, Biophysics and Molecular Biology, Ames, IA 50011, USA.
authors.forename: Edith M
authors.initials: EM
authors.lastname: Sampson
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Bobik
mesh_terms: D000433:1-Propanol / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D004269:DNA, Bacterial / Q000187:drug effects; D009154:Mutation; D015388:Organelles / Q000378:metabolism*; D011422:Propionates / Q000378:metabolism; D019946:Propylene Glycol / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D014805:Vitamin B 12 / Q000378:metabolism*
chemical_list: D000447:Aldehydes; D004269:DNA, Bacterial; D011422:Propionates; D019946:Propylene Glycol; D000433:1-Propanol; C005556:propionaldehyde; D014805:Vitamin B 12