title: Antimicrobial natural products as beta-ketoacyl-acyl carrier protein synthase III inhibitors.
abstract: Beta-ketoacyl-acyl carrier protein synthase III (KAS III) initiates bacterial fatty acid biosynthesis, making it one of the most promising condensing enzymes. In a previous study, we developed three pharmacophore maps from receptor-oriented pharmacophore-based in silico screening and proposed a potent antimicrobial inhibitor for KAS III. Using these pharmacophore maps, we examined a natural product database and chose 4 natural compounds as possible KAS III inhibitors. Here, we propose that YKAF01 (3,6-dihydroxyflavone) and YKAF04, 3-(4-hydroxyphenyl)-1-(2,4,6-tri-hydroxyphenyl)propan-1-one (or 4,2',4',6'-tetra-hydroxychalcone, phloretin) are potent antimicrobial inhibitors of KAS III with high binding affinity. In particular, these compounds display an excellent antimicrobial effect against Staphylococcus aureus and MRSA in the range of 16-32 microM.
authors: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, 1 Hwayang-dong, Kwangjin-gu, Seoul 143-701, Republic of Korea.
authors: Jee-Young
authors: JY
authors: Lee
authors: Ki-Woong
authors: KW
authors: Jeong
authors: Soyoung
authors: S
authors: Shin
authors: Ju-Un
authors: JU
authors: Lee
authors: Yangmee
authors: Y
authors: Kim
mesh_terms: D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D008958:Models, Molecular; D015394:Molecular Structure; D010693:Phloretin / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D011485:Protein Binding; D013050:Spectrometry, Fluorescence; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development
chemical_list: D000890:Anti-Infective Agents; D005419:Flavonoids; C077402:3-ketoacyl-acyl carrier protein synthase III; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase; D010693:Phloretin