These authors contributed equally to the work.
Biosynthesis of mycobacterial arabinogalactan: identification of a novel α(1→3) arabinofuranosyltransferase
Article first published online: 4 JUL 2008
© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd
Volume 69, Issue 5, pages 1191–1206, September 2008
How to Cite
Birch, H. L., Alderwick, L. J., Bhatt, A., Rittmann, D., Krumbach, K., Singh, A., Bai, Y., Lowary, T. L., Eggeling, L. and Besra, G. S. (2008), Biosynthesis of mycobacterial arabinogalactan: identification of a novel α(1→3) arabinofuranosyltransferase. Molecular Microbiology, 69: 1191–1206. doi: 10.1111/j.1365-2958.2008.06354.x
Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
- Issue published online: 5 AUG 2008
- Article first published online: 4 JUL 2008
- Accepted 17 June, 2008.
The cell wall mycolyl-arabinogalactan–peptidoglycan complex is essential in mycobacterial species, such as Mycobacterium tuberculosis and is the target of several antitubercular drugs. For instance, ethambutol targets arabinogalactan biosynthesis through inhibition of the arabinofuranosyltransferases Mt-EmbA and Mt-EmbB. A bioinformatics approach identified putative integral membrane proteins, MSMEG2785 in Mycobacterium smegmatis, Rv2673 in Mycobacterium tuberculosis and NCgl1822 in Corynebacterium glutamicum, with 10 predicted transmembrane domains and a glycosyltransferase motif (DDX), features that are common to the GT-C superfamily of glycosyltransferases. Deletion of M. smegmatis MSMEG2785 resulted in altered growth and glycosyl linkage analysis revealed the absence of AG α(1→3)-linked arabinofuranosyl (Araf) residues. Complementation of the M. smegmatis deletion mutant was fully restored to a wild-type phenotype by MSMEG2785 and Rv2673, and as a result, we have now termed this previously uncharacterized open reading frame, arabinofuranosyltransferase C (aftC). Enzyme assays using the sugar donor β-d-arabinofuranosyl-1-monophosphoryl-decaprenol (DPA) and a newly synthesized linear α(1→5)-linked Ara5 neoglycolipid acceptor together with chemical identification of products formed, clearly identified AftC as a branching α(1→3) arabinofuranosyltransferase. This newly discovered glycosyltransferase sheds further light on the complexities of Mycobacterium cell wall biosynthesis, such as in M. tuberculosis and related species and represents a potential new drug target.