Regulation of the Expression of Genes Involved in NAD De Novo Biosynthesis in Corynebacterium glutamicum

Three genes,nadA ,nadB , andnadC , involved in NADde novo biosynthesis are broadly conserved in the genomes of numerous bacterial species. In the genome ofCorynebacterium glutamicum ,nadA andnadC but notnadB are annotated. ThenadA andnadC genes are located in a gene cluster containing two other genes, designatedndnR andnadS herein.ndnR encodes a member of the Nudix-related transcriptional regulator (NrtR) family.nadS encodes a homologue of cysteine desulfurase involved in Fe-S cluster assembly. The gene clusterndnR -nadA -nadC -nadS is genetically characterized herein. Mutant strains deficient innadA ,nadC , ornadS required exogenous nicotinate for growth, and the nicotinate auxotrophy was complemented by introduction of the corresponding gene intrans , indicating that each of these genes is essential for growth in the absence of an exogenous source of NAD biosynthesis. The results of reverse transcriptase PCR analyses andndnR promoter-lacZ expression analyses revealed that the expression ofndnR ,nadA ,nadC , andnadS genes was markedly and coordinately repressed by nicotinate. The expression of these genes was enhanced by the disruption ofndnR , resulting in the loss of the nicotinate-responsive regulation of gene expression. These results suggest that NdnR acts as a transcriptional repressor of NADde novo biosynthesis genes and plays an essential role in the regulation of the response to nicotinate.