The biosynthetic interconnections between the arabinogalactan and glycopeptidolipid pathways in M. abscessus. dTDP-L-Rha is generated by the successive action of the Rml pathway enzymes, consisting of RmlA (MAB_4113), RmlB (MAB_3779), RmlC (MAB_3780), and RmlD (MAB_3613c). This dTDP-L-Rha is used by WbbL (MAB_3612c) to produce the Rha-N-acetyl-glucosaminyl-phosphate disaccharide unit that cross-links arabinogalactan to peptidoglycan. In addition, dTDP-L-Rha is also used by Gtf2 (MAB_4104) and Gtf3 (MAB_4112c) for GPL rhamnosylation (blue arrows). dTDP-6-d-Tal, produced from dTDP-L-Rha by the dTDP-Rha-4-epimerase (MAB_4111c/Tle) serves as the substrate for the talosyltransferase Gtf1 (green arrows), which adds one 6-d-Tal unit to mono- or di-rhamnosylated GPL precursors. The glycosylated GPL (GPL-2a and GPL-3) are then transported across the inner membrane by the MmpL4 complex (MAB_4116c, MAB_4115c, MAB_4117c) and inserted into the outer leaflet of the mycomembrane in the M. abscessus S variant.
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