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J. Bacteriol. doi:10.1128/JB.00703-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Control of methionine synthesis and uptake by MetR and homocysteine in Streptococcus mutans

Laboratoire de Génétique Microbienne, Institut National de la Recherche Agronomique, 78352 Jouy-en-Josas cedex, France; Unité de Génétique des Génomes bactériens, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France and UFR de Biochimie, Université Paris 7, 2 Place Jussieu, 75251 Paris, France

^* To whom correspondence should be addressed. Email: eric.guedon{at}jouy.inra.fr.

	Abstract

MetR (formerly Smu.1225), a regulator of the LysR family, controls key genes for methionine supply in Streptococcus mutans. A S. mutans metR mutant is unable to transport L-methionine and to grow in absence of this amino acid. Accordingly, MetR activates transcription by binding to the promoter region of two gene clusters and smu.1487 involved in methionine biosynthesis (MetEF, Smu.1487) and uptake (AtmBDE). Transcriptional activation by MetR requires the presence of a 17-bp palindromic sequence, the Met-box. Base substitutions in the Met-box hinder the formation of a MetR-DNA complex and abolish the MetR-dependent activation, showing that Met-boxes correspond to MetR recognition sites. Activation by MetR is observed in methionine depleted medium and is rapidly triggered under non-activating conditions by the addition of homocysteine. This intermediate of methionine biosynthesis increases the DNA affinity of MetR in vitro and appears to be the MetR co-effector in vivo. Homocysteine plays a crucial role in methionine metabolic gene regulation by controlling MetR activity. A similar homocysteine and MetR-dependent control of methionine biosynthetic genes also operates in S. thermophilus. These data suggest a common mechanism for the regulation of methionine supply in Streptococci. However, some Streptococcal species are unable to synthesize the homocysteine co-effector. This intriguing feature is discussed in the light of comparative genomics and Streptococcal ecology.

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