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 .
申请公布号
WO0181307(A3)
申请公布日期
2002.07.18
申请号
WO2001US13312
申请日期
2001.04.25
申请人
WISCONSIN ALUMNI RESEARCH FOUNDATION
发明人
HANDELSMAN, JO, E.;GOODMAN, ROBERT, M.;GILLESPIE, DOREEN, E.;BETTERMANN, ALAN, D.;CLARDY, JON, C.;BRADY, SEAN, F.