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.