title: Fatty acid synthesis is a target for antibacterial activity of unsaturated fatty acids.
abstract: Long-chain unsaturated fatty acids, such as linoleic acid, show antibacterial activity and are the key ingredients of antimicrobial food additives and some antibacterial herbs. However, the precise mechanism for this antimicrobial activity remains unclear. We found that linoleic acid inhibited bacterial enoyl-acyl carrier protein reductase (FabI), an essential component of bacterial fatty acid synthesis, which has served as a promising target for antibacterial drugs. Additional unsaturated fatty acids including palmitoleic acid, oleic acid, linolenic acid, and arachidonic acid also exhibited the inhibition of FabI. However, neither the saturated form (stearic acid) nor the methyl ester of linoleic acid inhibited FabI. These FabI-inhibitory activities of various fatty acids and their derivatives very well correlated with the inhibition of fatty acid biosynthesis using [(14)C] acetate incorporation assay, and importantly, also correlated with antibacterial activity. Furthermore, the supplementation with exogenous fatty acids reversed the antibacterial effect of linoleic acid, which showing that it target fatty acid synthesis. Our data demonstrate for the first time that the antibacterial action of unsaturated fatty acids is mediated by the inhibition of fatty acid synthesis.
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology, P.O. Box 115, Yusong, Daejeon 305-600, Republic of Korea.
authors.forename: Chang Ji
authors.initials: CJ
authors.lastname: Zheng
authors.forename: Jung-Sung
authors.initials: JS
authors.lastname: Yoo
authors.forename: Tae-Gyu
authors.initials: TG
authors.lastname: Lee
authors.forename: Hee-Young
authors.initials: HY
authors.lastname: Cho
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Won-Gon
authors.initials: WG
authors.lastname: Kim
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001419:Bacteria / Q000737:chemistry / Q000378:metabolism; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH); D005227:Fatty Acids / Q000096:biosynthesis* / Q000737:chemistry; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D010088:Oxidoreductases; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)