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J. Bacteriol. doi:10.1128/JB.01027-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Computational prediction and experimental verification of the gene encoding the NAD⁺/NADP⁺-dependent succinate semialdehyde dehydrogenase in Escherichia coli

Institute of Molecular Systems Biology, ETH Zurich, CH-8093 Zurich, Switzerland; Center for Computational Biology and Bioinformatics and Department of Biomedical Informatics, Columbia University, 1130 Nicholas Ave., Irving Cancer Research Center, New York, NY 10032, USA

^* To whom correspondence should be addressed. Email: sauer{at}imsb.biol.ethz.ch. dv2121{at}columbia.edu.

	Abstract

Although the 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 an earlier developed gap-filling algorithm in metabolic networks, 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 general nitrogen metabolism of E. coli. In particular we demonstrate by mutant growth experiments that the yneI gene has an important, but not essential, role during growth on arginine and probably 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. The yneI-encoded activity, in contrast, functions primarily as a valve to prevent toxic accumulation of succinate semialdehyde. Analysis of available genome sequences demonstrates that orthologs of both yneI and gabD are broadly distributed across phylogenetic space.