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Journal of Bacteriology, July 2008, p. 4849-4858, Vol. 190, No. 14
0021-9193/08/$08.00+0     doi:10.1128/JB.00185-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

NrdI Essentiality for Class Ib Ribonucleotide Reduction in Streptococcus pyogenes ^,

Grup de Genètica Molecular Bacteriana, Institut de Biotecnologia i de Biomedicina, and Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08913 Barcelona, Spain,¹ Department of Molecular Biology and Functional Genomics, Arrhenius Laboratories, Stockholm University, SE-10691 Stockholm, Sweden,² Institute for Bioengineering of Catalonia (IBEC), Scientific Park of Barcelona, Edifici Hèlix, Baldiri Reixac 15-21, ES-08028 Barcelona, Spain³

Received 6 February 2008/ Accepted 14 May 2008

The Streptococcus pyogenes genome harbors two clusters of class Ib ribonucleotide reductase genes, nrdHEF and nrdF*I*E*, and a second stand-alone nrdI gene, designated nrdI2. We show that both clusters are expressed simultaneously as two independent operons. The NrdEF enzyme is functionally active in vitro, while the NrdE*F* enzyme is not. The NrdF* protein lacks three of the six highly conserved iron-liganding side chains and cannot form a dinuclear iron site or a tyrosyl radical. In vivo, on the other hand, both operons are functional in heterologous complementation in Escherichia coli. The nrdF*I*E* operon requires the presence of the nrdI* gene, and the nrdHEF operon gained activity upon cotranscription of the heterologous nrdI gene from Streptococcus pneumoniae, while neither nrdI* nor nrdI2 from S. pyogenes rendered it active. Our results highlight the essential role of the flavodoxin NrdI protein in vivo, and we suggest that it is needed to reduce met-NrdF, thereby enabling the spontaneous reformation of the tyrosyl radical. The NrdI* flavodoxin may play a more direct role in ribonucleotide reduction by the NrdF*I*E* system. We discuss the possibility that the nrdF*I*E* operon has been horizontally transferred to S. pyogenes from Mycoplasma spp.

Published ahead of print on 23 May 2008.

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

This article has been cited by other articles:

• Cotruvo, J. A. Jr., Stubbe, J. (2008). NrdI, a flavodoxin involved in maintenance of the diferric-tyrosyl radical cofactor in Escherichia coli class Ib ribonucleotide reductase. Proc. Natl. Acad. Sci. USA 105: 14383-14388 [Abstract] [Full Text]