title: The Lactone form of stachybotrydial: a new inhibitor of dihydrofolate reductase from stachybotrys sp. FN298.
abstract: Dihydrofolate reductase (DHFR) has been confirmed to be a novel target for antibacterial drug development. In this study, we determined that a fungal metabolite from Stachybotrys sp. FN298 can inhibit the DHFR of Staphylococcus aureus. Its structure was identified as a lactone form of stachybotrydial using mass spectrometry and nuclear magnetic resonance analysis. This compound inhibited S. aureus DHFR with a half-maximal inhibitory concentration of 41 µM. It also prevented the growth of S. aureus and methicillin-resistant S. aureus (MRSA) with a minimum inhibitory concentration of 32 µg·mL(-1). To our knowledge, this is the first description of a DHFR inhibitor of microbial origin. The inhibitory function of the lactone form of stachybotrydial highlights its potential for development into a new broad-spectrum antibacterial agent and as an agent against MRSA.
authors.affiliation: Superbacteria Research Center, Korea Research Institute of Bioscience and Biotechnology.
authors.forename: Yun-Ju
authors.initials: YJ
authors.lastname: Kwon
authors.forename: Mi-Jin
authors.initials: MJ
authors.lastname: Sohn
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Kim
authors.forename: Won-Gon
authors.initials: WG
authors.lastname: Kim
mesh_terms: D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001572:Benzofurans / Q000737:chemistry*; D004269:DNA, Bacterial / Q000096:biosynthesis; D005493:Folic Acid Antagonists / Q000302:isolation & purification / Q000494:pharmacology*; D007783:Lactones / Q000302:isolation & purification / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D012329:RNA, Bacterial / Q000096:biosynthesis; D013141:Spiro Compounds / Q000737:chemistry*; D013191:Stachybotrys / Q000737:chemistry / Q000302:isolation & purification; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001572:Benzofurans; D004269:DNA, Bacterial; D005493:Folic Acid Antagonists; D007783:Lactones; D012329:RNA, Bacterial; D013141:Spiro Compounds; C094818:stachybotrydial; D013762:Tetrahydrofolate Dehydrogenase