Regulation of NAD biosynthesis in Salmonella typhimurium: expression of nad-lac gene fusions and identification of a nad regulatory locus.

Regulation of NAD biosynthesis was examined through the construction of nad-lac fusions in Salmonella typhimurium. The nadA (17 unit map position) and nadB (55 units) genetic loci involved with quinolinic acid biosynthesis were both found to be regulated by the product of a nadR locus (99 units) in a repression/derepression manner while nadC (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-amino NAD was ineffective in repressing either nadA or nadB. The presence of cAMP + cAMP receptor protein was essential for the complete derepression of nadA while no effect was evident upon nadB. Transfer of cultures from aerobic to anaerobic conditions, however, resulted in the partial derepression of both nadA and nadB. Thus, there appears to be a very complex set of controls regulating NAD biosynthesis.