The iscS gene deficiency affects the expression of pyrimidine metabolism genes

Inactivation of iscS encoding cysteine desulfurase results in a slow growth phenotype associated with the deficiency of iron–sulfur clusters, thiamine, NAD, and tRNA thionucleosides in Escherichia coli. However, the other roles of iscSin vivo are unknown. By using differential screening strategies, we identified 2 pyrimidine salvage enzymes, namely, uridine phosphorylase and cytidine deaminase, which were down-regulated in the iscS mutant. Both enzymes are positively regulated by the cAMP receptor protein (CRP). We also identified a novel protein complex, namely, YeiT–YeiA, whose expression level was decreased in the iscS mutant. The recombinant YeiT–YeiA complex exhibited NADH-dependent dihydropyrimidine dehydrogenase activity, indicating its role in pyrimidine metabolism. The presence of a CRP-binding consensus sequence on the 5′-upstream of the yeiT–YeiA gene suggests its regulation by CRP. These results provide a clue to the possible role of iscS in pyrimidine metabolism by gene regulation.