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1. (WO2001081307) TRIARYL CATION ANTIBIOTICS FROM ENVIRONMENTAL DNA

Pub. No.:    WO/2001/081307    International Application No.:    PCT/US2001/013312
Publication Date: Nov 1, 2001 International Filing Date: Apr 25, 2001
IPC: A61K 31/404
C07D 209/14
C12N 15/52
C12P 17/16
Applicants: WISCONSIN ALUMNI RESEARCH FOUNDATION
Inventors: HANDELSMAN, Jo, E.
GOODMAN, Robert, M.
GILLESPIE, Doreen, E.
BETTERMANN, Alan, D.
CLARDY, Jon, C.
BRADY, Sean, F.
Title: TRIARYL CATION ANTIBIOTICS FROM ENVIRONMENTAL DNA
Abstract:
Disclosed are triaryl cationic compounds that exhibit broad-spectrum antibiotic and antifungal activity, pharmaceutical compositions containing the compounds, and methods of treating bacterial and fungal infections using the compounds. The compounds were initially isolated by screening a 25,000-member bacterial artificial chromosome (BAC) library of environmental (eDNA) from soil. At least one clone produced a dark brown melanin-like compounds that was found to have antibiotic activity. The compounds were isolated and synthesized de novo. From within the positive clone, a single open reading frame that shares extensive sequence similarity with members of the 4-hydroxyphenylpyruvate family of enzymes was found to be necessary and sufficient to confer the production of at least one of the subject compound on E. Coli.