Modification of glycopeptidolipids by an O-methyltransferase of Mycobacterium smegmatis

Glycopeptidolipids (GPLs) are a major component of the outer layers of the cell walls of several non-tuberculous mycobacteria. The Mycobacterium smegmatis GPLs consist of a diglycosylated lipopeptide core which is variably modified by acetylation and methylation. Analysis of a region of the M. smegmatis chromosome, upstream of the peptide synthetase gene, mps, revealed a GPL biosynthetic locus containing genes potentially involved in glycosylation, methylation, acetylation and transport of GPLs. Methyltransferases are required to modify rhamnose and the fatty acid of GPLs. Of the four methyltransferases encoded within the locus, one methyltransferase, Mtf2, was unlike sugar methyltransferases from other species. An mtf2 mutant was created and was shown to be unable to methylate the GPL fatty acids. Direct evidence is presented that Mtf2 is a methyltransferase that modifies the GPL faty acid.