American Chemical Society
np800528a_si_001.pdf (1.32 MB)

Antisense-Guided Isolation and Structure Elucidation of Pannomycin, a Substituted cis-Decalin from Geomyces pannorum

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journal contribution
posted on 2009-01-23, 00:00 authored by Craig A. Parish, Mercedes de la Cruz, Scott K. Smith, Deborah Zink, Jenny Baxter, Samantha Tucker-Samaras, Javier Collado, Gonzalo Platas, Gerald Bills, Maria Teresa Díez, Francisca Vicente, Fernando Peláez, Kenneth Wilson
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.