Structure, Biosynthesis, and Genetics of the Mycolic Acid‐Arabinogalactan‐Peptidoglycan Complex

Abstract

The cell envelope of Mycobacterium tuberculosis is made up of three major components: a plasma membrane; a covalently linked complex of mycolic acid-arabinogalactan-peptidoglycan complex (MAPc); and a polysaccharide-rich capsule-like layer. It is felt that knowledge of the biosynthesis and genetics of this aspect of the cell wall biogenesis may provide insight into overall cell wall architecture, particularly the relationship between its soluble components and the insoluble MAPc. PG biosynthesis in Escherichia coli can be divided into three stages based on subcellular localization. Of the other enzymes related to UDP-MurNAcpentapeptide synthesis in mycobacteria, the D-alanine racemase and D-alanine:D-alanine ligase from Mycobacterium smegmatis have been studied. Analysis of the genome of M. tuberculosis reveals the presence of a repertoire of putative penicillin binding proteins (PBPs), of which only a few have been characterized. The arabinogalactan (AG) biosynthetic pathway has been investigated mainly in M. smegmatis and M. tuberculosis. The arabinofuranose (Araf ) residues of arabinan are added to the linker unit-galactan polymer from a decaprenylphosphoryl-Araf (DPA) precursor. The ligation of arabinogalactan (AG) to peptidoglycan (PG) has been demonstrated in experiments with cell-free preparations of M. smegmatis, and the nature of in vitro-synthesized material was confirmed by the observation that the newly ligated AG can be released from PG by muramidase treatment.