title: Antisense-guided isolation and structure elucidation of pannomycin, a substituted cis-decalin from Geomyces pannorum.
abstract: Antisense-based screening strategies can be used to sensitize a microorganism and selectively detect inhibitors against a particular cellular target of interest. A strain of Staphylococcus aureus that generates an antisense RNA against SecA,a central member of the protein secretion machinery, has been used to screen for novel antibacterials. Possible inhibitors of the SecA ATP-ase were selected with a high-throughput, two-plate agar-based whole cell differential sensitivity screen. After screening a library of over 115 000 natural products extracts with the SecA antisense strain, an extract of Geomyces pannorum was identified as providing increased activity against the sensitized strain as compared with the wild-type control. Bioassay-guided isolation of the active component from this fungal extract provided a new cis-decalin secondary metabolite, which we have named pannomycin.
authors.affiliation: Merck Research Laboratories, Rahway, New Jersey 07065, USA. craig_parish@merck.com
authors.forename: Craig A
authors.initials: CA
authors.lastname: Parish
authors.forename: Mercedes
authors.initials: M
authors.lastname: de la Cruz
authors.forename: Scott K
authors.initials: SK
authors.lastname: Smith
authors.forename: Deborah
authors.initials: D
authors.lastname: Zink
authors.forename: Jenny
authors.initials: J
authors.lastname: Baxter
authors.forename: Samantha
authors.initials: S
authors.lastname: Tucker-Samaras
authors.forename: Javier
authors.initials: J
authors.lastname: Collado
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Platas
authors.forename: Gerald
authors.initials: G
authors.lastname: Bills
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Díez
authors.forename: Francisca
authors.initials: F
authors.lastname: Vicente
authors.forename: Fernando
authors.initials: F
authors.lastname: Peláez
authors.forename: Kenneth
authors.initials: K
authors.lastname: Wilson
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001203:Ascomycota / Q000737:chemistry*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors; D026901:Membrane Transport Proteins; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D016372:RNA, Antisense / Q000235:genetics* / Q000378:metabolism; D000069816:SEC Translocation Channels; D000081416:SecA Proteins; D013211:Staphylococcus aureus / Q000187:drug effects; D013237:Stereoisomerism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D009281:Naphthalenes; D016372:RNA, Antisense; D000069816:SEC Translocation Channels; C534923:pannomycin; D000251:Adenosine Triphosphatases; D000081416:SecA Proteins