Deacylation of echinocandin B by Actinoplanes utahensis

Abstract

Echinocandin B (ECB) is a lipopeptide antifungal agent produced by several species of Aspergillus. The lipid side chain of cyclic lipopeptides is known to be an important determinant of their antibiotic activity and toxicity. Deacylation of another lipopeptide antibiotic, A21978C, had formerly been accomplished with Actinoplanes utahensis. In spite of the structural dissimilarities between the peptide cores and acyl side chains of A21978C and ECB, A. utahensis also removed the linoleoyl acyl unit from the amino terminus of ECB to yield the bioinactive cyclic peptide core, or "nucleus". The ECB nucleus, which contained a new titratable group at the N-terminus, was subsequently employed for chemical reacylation with other side chains to yield a variety of novel ECB analogs. One of these, cilofungin (LY121019), containing an N-(4-n-octyloxybenzoyl)acyl unit, is currently undergoing clinical evaluation.