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Nucleic Acids Research 2004 32(11):3340-3353; doi:10.1093/nar/gkh659
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Published online 23 June 2004

Nucleic Acids Research, Vol. 32 No. 11 © Oxford University Press 2004; all rights reserved

Comparative genomics of the methionine metabolism in Gram-positive bacteria: a variety of regulatory systems

Dmitry A. Rodionov1,2,*, Alexey G. Vitreschak1, Andrey A. Mironov2,3 and Mikhail S. Gelfand1,2,3

1 Institute for Information Transmission Problems, Russian Academy of Sciences, Bolshoi Karetny pereulok 19, Moscow 127994, Russia, 2 State Scientific Center GosNIIGenetika, Moscow 117545, Russia and 3 Department of Bioengineering and Bioinformatics, Moscow State University, Moscow 119992, Russia

* To whom correspondence should be addressed at Institute for Information Transmission Problems, Russian Academy of Sciences, Bolshoi Karetny pereulok 19, Moscow 127994, Russia. Tel: +7 095 3150156; Fax: +7 095 1356080; Email: rodionov{at}genetika.ru

Received February 9, 2004; Revised March 22, 2004; Accepted June 2, 2004

Regulation of the methionine biosynthesis and transport genes in bacteria is rather diverse and involves two RNA-level regulatory systems and at least three DNA-level systems. In particular, the methionine metabolism in Gram-positive bacteria was known to be controlled by the S-box and T-box mechanisms, both acting on the level of premature termination of transcription. Using comparative analysis of genes, operons and regulatory elements, we described the methionine metabolic pathway and the methionine regulons in available genomes of Gram-positive bacteria. A large number of methionine-specific RNA elements were identified. S-boxes were shown to be widely distributed in Bacillales and Clostridia, whereas methionine-specific T-boxes occurred mostly in Lactobacillales. A candidate binding signal (MET-box) for a hypothetical methionine regulator, possibly MtaR, was identified in Streptococcaceae, the only family in the Bacillus/Clostridium group of Gram-positive bacteria having neither S-boxes, nor methionine-specific T-boxes. Positional analysis of methionine-specific regulatory sites complemented by genome context analysis lead to identification of new members of the methionine regulon, both enzymes and transporters, and reconstruction of the methionine metabolism in various bacterial genomes. In particular, we found candidate transporters for methionine (MetT) and methylthioribose (MtnABC), as well as new enzymes forming the S-adenosylmethionine recycling pathway. Methionine biosynthetic enzymes in various bacterial species are quite variable. In particular, Oceanobacillus iheyensis possibly uses a homolog of the betaine–homocysteine methyltransferase bhmT gene from vertebrates to substitute missing bacterial-type methionine synthases.


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