A unique phenylalanine-containing lipopeptide isolated from a rough-colony variant of Mycobacterium avium

Previous investigations have suggested that the biosynthesis of the Mycobacterium avium serovar-specific glycopeptidolipid antigens involves initial steps that include the participation of lipopeptides. The prevailing assumption is that subsequent glycosylation of those lipopeptides results in the fully glycosylated form of the glycopeptidolipid components. In an effort to identify potential precursors in the biosynthetic pathway of glycopeptidolipid components, we have identified a unique lipopeptide from an M. avium rough variant (MAC702) that was isolated from a patient suffering from a chronic M. avium lung infection. Upon examination it was revealed that although the total lipid extract from MAC702 lacked serovar-specific glycopeptidolipid antigens, it did contain a unique lipopeptide, possessing some amino acids identical to those found in the serovar-specific glycopeptidolipid antigens. Initial examination of acid-hydrolyzed samples of the lipopeptide (lipopeptide-I) revealed the presence of phenylalanine, alanine, and isoleucine, but no carbohydrate. Subsequent mass spectrometric and 1H-NMR and 1H-13C-NMR correlation spectroscopy analysis confirmed the initial results and also revealed the presence of N-methylisoleucine. The following structure for lipopeptide-I was proposed: fatty acyl (C19 or C17)-Phe-N-methyl-Ile-Ile-Phe-Ala-Ile-Ala-Phe. Lipopeptide-I is unlike any heretofore identified compound, however, it does have similar features to lipopeptides previously reported in mycobacteria and fungi. Although its structure does not verify that it is a direct precursor in glycopeptidolipid biosynthesis, the presence of certain components in lipopeptide-I indicate that it may share at least some pathways associated with the biosynthesis of the M. avium serovar-specific glycopeptidolipids.