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Journal of Bacteriology, November 2007, p. 7856-7876, Vol. 189, No. 21
0021-9193/07/$08.00+0     doi:10.1128/JB.00837-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Predicted Functions and Linkage Specificities of the Products of the Streptococcus pneumoniae Capsular Biosynthetic Loci ^,

David M. Aanensen,^1, Angeliki Mavroidi,^1, Stephen D. Bentley,² Peter R. Reeves,³ and Brian G. Spratt^1*

Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom,¹ Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom,² School of Molecular and Microbial Biosciences, University of Sydney, Sydney, Australia³

Received 30 May 2007/ Accepted 21 August 2007

The sequences of the capsular biosynthetic (cps) loci of 90 serotypes of Streptococcus pneumoniae have recently been determined. Bioinformatic procedures were used to predict the general functions of 1,973 of the 1,999 gene products and to identify proteins within the same homology group, Pfam family, and CAZy glycosyltransferase family. Correlating cps gene content with the 54 known capsular polysaccharide (CPS) structures provided tentative assignments of the specific functions of the different homology groups of each functional class (regulatory proteins, enzymes for synthesis of CPS constituents, polymerases, flippases, initial sugar transferases, glycosyltransferases [GTs], phosphotransferases, acetyltransferases, and pyruvyltransferases). Assignment of the glycosidic linkages catalyzed by the 342 GTs (92 homology groups) is problematic, but tentative assignments could be made by using this large set of cps loci and CPS structures to correlate the presence of particular GTs with specific glycosidic linkages, by correlating inverting or retaining linkages in CPS repeat units with the inverting or retaining mechanisms of the GTs predicted from their CAZy family membership, and by comparing the CPS structures of serotypes that have very similar cps gene contents. These large-scale comparisons between structure and gene content assigned the linkages catalyzed by 72% of the GTs, and all linkages were assigned in 32 of the serotypes with known repeat unit structures. Clear examples where very similar initial sugar transferases or glycosyltransferases catalyze different linkages in different serotypes were also identified. These assignments should provide a stimulus for biochemical studies to evaluate the reactions that are proposed.

Published ahead of print on 31 August 2007.

Supplemental material for this article may be found at http://jb.asm.org/.

D.M.A. and A.M. contributed equally to this work.

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