Fig. 1: Biosynthesis of mannosylated glycolipids in mycobacteria.

a The biosynthetic pathway for LM and LAM results in three primary products: PIMs, LM and LAM. The degree of acylation for each glycolipid can vary, as can secondary modifications on LM and LAM. An unknown process drives the expression of AM and M on the surface of the bacteria as part of their capsule. A simplified structure of LM/LAM is presented for clarity. The grey text indicates the presumed enzyme catalysing the reaction, and the black text indicates the glycolipid species. Several of the enzymes and the exact location for some steps in this process remain unknown. b Ribbon diagram of Aman6 (PDB:5AGD; grey) in complex with ɑ-1,6-mannotetraose aligned in ccp4i Superpose with the AlphaFold 2.0 predicted structure for LamH (Rv0365c) associated with its Uniprot entry (O06315; blue). c The confirmed catalytic residues in Aman6 (D124/D125; D125N mutant in 5AGD; grey) are conserved in LamH (D96/D97; blue). d Phylogenetic tree of GH76 enzymes from the Mycobacteriales. Genomes for all available members of the Mycobacteriales were used to generate a custom BLAST database in Geneious Prime 2023.1.1. LamH was used as a query in a BLAST search of this database, yielding high-confidence homologues from all species. This list of proteins was submitted to NGPhylogeny.fr using the PHYML/OneClick tool; the tree was then manually coloured to identify individual genera³⁷. Source data are provided as a Source Data file.