TRIARYL CATION ANTIBIOTICS FROM ENVIRONMENTAL DNA

摘要

Disclosed are triaryl cationic compounds that exhibit broad-spectrum antibiotic and antifungal activity, pharmaceutical compositions containing t he compounds, and methods of treating bacterial and fungal infections using the compounds. The compounds were initially isolated by screening a 25,000-membe r bacterial artificial chromosome (BAC) library of environmental (eDNA) from soil. At least one clone produced a dark brown melanin-like compounds that w as found to have antibiotic activity. The compounds were isolated and synthesiz ed 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.