Regulation of NAD Biosynthesis in Salmonella typhimurium: Expression of nad—lac Gene Fusions and Identification of a nad Regulatory Locus

Summary: Regulation of NAD biosynthesis was examined through the construction of nad—lac fusions in Salmonella typhimurium. The nad A (17 unit map position) and nad B (55 units) genetic loci involved with quinolinic acid biosynthesis were both found to be regulated by the product of a nad R locus (99 units) in a repression/derepression manner while nad C (3 units) expression appeared constitutive at the transcriptional level. Increases in nadAB transcription directly correlated with decreases in intracellular NAD(P) levels, and kinetic studies indicated that the NAD analogue 6-aminoNAD was ineffective in repressing either nad A or nad B. The presence of cAMP + cAMP receptor protein was essential for the complete derepression of nad A while no effect was evident upon nad B. Transfer of cultures from aerobic to anaerobic conditions, however, resulted in the partial derepression of both nad A and nad B. Thus, there appears to be a very complex set of controls regulating NAD biosynthesis.