KEGG   PATHWAY: map00571
Entry
map00571                    Pathway                                
Name
Lipoarabinomannan (LAM) biosynthesis
Description
Lipoarabinomannan (LAM), as well as structurally related lipomannan (LM) and phosphatidylinositol mannosides (PIMs), are major glycolipids found on the mycobacterial cell wall. LAM is synthesized from phosphatidylinositol (PI) and in a biochemical pathway of PI => PIMs => LM =>LAM. Structually, LAM and LM are an extension of PIMs containing an alpha1,6-linked mannan core with alpha1,2-monomannose side chains. The mannan core of LAM is in turn arabinosylated by a linear alpha1,5-linked Araf backbone, punctutated by alpha1,3-linked branching. LAM can be substituted by several capping motifs, which determine the ability of LAM to modulate the immune response through the interaction with different receptors containing C-type lectins (map04625). It has been shown that the immunomodulatory properties of LAM and related glycolipids contribute to the survival of Mycobacteriaum tuberculosis, the causative agent of tuberculosis (map05152).
Class
Metabolism; Glycan biosynthesis and metabolism
Pathway map
map00571  Lipoarabinomannan (LAM) biosynthesis
map00571

Reference
  Authors
Jankute M, Grover S, Birch HL, Besra GS
  Title
Genetics of Mycobacterial Arabinogalactan and Lipoarabinomannan Assembly.
  Journal
Microbiol Spectr 2:MGM2-0013-2013 (2014)
DOI:10.1128/microbiolspec.MGM2-0013-2013
Reference
  Authors
Morita YS, Patterson JH, Billman-Jacobe H, McConville MJ
  Title
Biosynthesis of mycobacterial phosphatidylinositol mannosides.
  Journal
Biochem J 378:589-97 (2004)
DOI:10.1042/BJ20031372
Reference
  Authors
Jankute M, Cox JA, Harrison J, Besra GS
  Title
Assembly of the Mycobacterial Cell Wall.
  Journal
Annu Rev Microbiol 69:405-23 (2015)
DOI:10.1146/annurev-micro-091014-104121
Reference
  Authors
Guerin ME, Kordulakova J, Alzari PM, Brennan PJ, Jackson M
  Title
Molecular basis of phosphatidyl-myo-inositol mannoside biosynthesis and regulation in mycobacteria.
  Journal
J Biol Chem 285:33577-83 (2010)
DOI:10.1074/jbc.R110.168328
Reference
  Authors
Briken V, Porcelli SA, Besra GS, Kremer L
  Title
Mycobacterial lipoarabinomannan and related lipoglycans: from biogenesis to modulation of the immune response.
  Journal
Mol Microbiol 53:391-403 (2004)
DOI:10.1111/j.1365-2958.2004.04183.x
Reference
  Authors
Alderwick LJ, Birch HL, Mishra AK, Eggeling L, Besra GS
  Title
Structure, function and biosynthesis of the Mycobacterium tuberculosis cell wall: arabinogalactan and lipoarabinomannan assembly with a view to discovering new drug targets.
  Journal
Biochem Soc Trans 35:1325-8 (2007)
DOI:10.1042/BST0351325
Reference
  Authors
Mishra AK, Driessen NN, Appelmelk BJ, Besra GS
  Title
Lipoarabinomannan and related glycoconjugates: structure, biogenesis and role in Mycobacterium tuberculosis physiology and host-pathogen interaction.
  Journal
FEMS Microbiol Rev 35:1126-57 (2011)
DOI:10.1111/j.1574-6976.2011.00276.x
Reference
  Authors
Morita YS, Sena CB, Waller RF, Kurokawa K, Sernee MF, Nakatani F, Haites RE, Billman-Jacobe H, McConville MJ, Maeda Y, Kinoshita T
  Title
PimE is a polyprenol-phosphate-mannose-dependent mannosyltransferase that transfers the fifth mannose of phosphatidylinositol mannoside in mycobacteria.
  Journal
J Biol Chem 281:25143-55 (2006)
DOI:10.1074/jbc.M604214200
Reference
  Authors
Batt SM, Jabeen T, Mishra AK, Veerapen N, Krumbach K, Eggeling L, Besra GS, Futterer K
  Title
Acceptor substrate discrimination in phosphatidyl-myo-inositol mannoside synthesis: structural and mutational analysis of mannosyltransferase Corynebacterium glutamicum PimB'.
  Journal
J Biol Chem 285:37741-52 (2010)
DOI:10.1074/jbc.M110.165407
Reference
  Authors
Boonyarattanakalin S, Liu X, Michieletti M, Lepenies B, Seeberger PH
  Title
Chemical synthesis of all phosphatidylinositol mannoside (PIM) glycans from Mycobacterium tuberculosis.
  Journal
J Am Chem Soc 130:16791-9 (2008)
DOI:10.1021/ja806283e
Reference
  Authors
Guerardel Y, Maes E, Elass E, Leroy Y, Timmerman P, Besra GS, Locht C, Strecker G, Kremer L
  Title
Structural study of lipomannan and lipoarabinomannan from Mycobacterium chelonae. Presence of unusual components with alpha 1,3-mannopyranose side chains.
  Journal
J Biol Chem 277:30635-48 (2002)
DOI:10.1074/jbc.M204398200
Related
pathway
map00564  Glycerophospholipid metabolism
map04625  C-type lectin receptor signaling pathway
map05152  Tuberculosis
KO pathway
ko00571   
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