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Biosynthesis of mycobacterial arabinogalactan: identification of a novel a(1,3)arabinofuranosyltransferase

Birch, Helen and Alderwick, Luke J. and Bhatt, Apoorva and Rittmann, Doris and Krumbach, Karin and Singh, Albel and Bai, Yu and Lowary, Todd L. and Eggeling, Lothar and Besra, Gurdyal S (2008) Biosynthesis of mycobacterial arabinogalactan: identification of a novel a(1,3)arabinofuranosyltransferase. Molecular Microbiology, 69 (5). pp. 1191-1206. ISSN 0950-382X

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URL of Published Version: http://www3.interscience.wiley.com/journal/120696449/abstract?CRETRY=1&SRETRY=0

Identification Number/DOI: 10.1111/j.1365-2958.2008.06354.x

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 SMEG2785 resulted in altered growth and glycosyl linkage analysis revealed the absence of AG a(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 b-D-arabinofuranosyl-1-
monophosphoryl-decaprenol (DPA) and a newly synthesized linear a(1,5)-linked Ara5 neoglycolipid acceptor together with chemical identification of products formed, clearly identified AftC as a branching a(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.

Type of Work:Article
Date:15 July 2008 (Publication)
School/Faculty:Schools (1998 to 2008) > School of Biosciences
Department:Molecular Microbiology
Subjects:QR Microbiology
Institution:University of Birmingham
Copyright Holders:Blackwell Publishing
ID Code:118
Refereed:YES
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