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Journal of Bacteriology, November 2007, p. 8073-8078, Vol. 189, No. 22
0021-9193/07/$08.00+0     doi:10.1128/JB.01027-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Computational Prediction and Experimental Verification of the Gene Encoding the NAD⁺/NADP⁺-Dependent Succinate Semialdehyde Dehydrogenase in Escherichia coli ^,

Tobias Fuhrer,^1, Lifeng Chen,^2, Uwe Sauer,^1* and Dennis Vitkup^2*

Institute of Molecular Systems Biology, ETH Zurich, CH-8093 Zurich, Switzerland,¹ Center for Computational Biology and Bioinformatics and Department of Biomedical Informatics, Columbia University, 1130 Nicholas Ave., Irving Cancer Research Center, New York, New York 10032²

Received 29 June 2007/ Accepted 3 September 2007

Although NAD⁺-dependent succinate semialdehyde dehydrogenase activity was first described in Escherichia coli more than 25 years ago, the responsible gene has remained elusive so far. As an experimental proof of concept for a gap-filling algorithm for metabolic networks developed earlier, we demonstrate here that the E. coli gene yneI is responsible for this activity. Our biochemical results demonstrate that the yneI-encoded succinate semialdehyde dehydrogenase can use either NAD⁺ or NADP⁺ to oxidize succinate semialdehyde to succinate. The gene is induced by succinate semialdehyde, and expression data indicate that yneI plays a unique physiological role in the general nitrogen metabolism of E. coli. In particular, we demonstrate using mutant growth experiments that the yneI gene has an important, but not essential, role during growth on arginine and probably has an essential function during growth on putrescine as the nitrogen source. The NADP⁺-dependent succinate semialdehyde dehydrogenase activity encoded by the functional homolog gabD appears to be important for nitrogen metabolism under N limitation conditions. The yneI-encoded activity, in contrast, functions primarily as a valve to prevent toxic accumulation of succinate semialdehyde. Analysis of available genome sequences demonstrated that orthologs of both yneI and gabD are broadly distributed across phylogenetic space.

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* Corresponding author. Mailing address for Dennis Vitkup: Center for Computational Biology and Bioinformatics and Department of Biomedical Informatics, Columbia University, 1130 Nicholas Ave., Irving Cancer Research Center, New York, NY 10032. Phone: (212) 851-5151. Fax: (212) 851-5149. E-mail: dv2121{at}columbia.edu. Mailing address for Uwe Sauer: Institute of Molecular Systems Biology, ETH Zurich, CH-8093 Zurich, Switzerland. Phone: 41 44 633 3672. Fax: 41 44 633 1051. E-mail: sauer{at}imsb.biol.ethz.ch

Published ahead of print on 14 September 2007.

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

T.F. and L.C. contributed equally to this work.

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Journal of Bacteriology, November 2007, p. 8073-8078, Vol. 189, No. 22
0021-9193/07/$08.00+0     doi:10.1128/JB.01027-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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