Assimilation of Nicotinamide Mononucleotide Requires Periplasmic

Salmonella enterica can obtain pyridine from exogenous nicotinamide mononucleotide (NMN) by three routes. In route 1, nicotinamide is removed from NMN in the periplasm and enters the cell as the free base. In route 2, described here, phosphate is removed from NMN in the periplasm by acid phosphatase (AphA), and the produced nicotinamide ribonucleoside (NmR) enters the cell via the PnuC transporter. Internal NmR is then converted back to NMN by the NmR kinase activity of NadR. Route 3 is seen only in pnuC * transporter mutants, which import NMN intact and can therefore grow on lower levels of NMN. Internal NMN produced by either route 2 or route 3 is deamidated to nicotinic acid mononucleotide and converted to NAD by the biosynthetic enzymes NadD and NadE. The pyridine cofactors NAD and NADP are electron carri-ers that are essential for both catabolic and biosynthetic redox reactions. In addition, NAD is used by bacterial DNA ligase to activate single-strand ends prior to joining (25, 49) and serves as a precursor of cofactor B12 (23). NAD can also serve as an acceptor of an acetyl group in protein deacetylation (38). Fig-ure 1 shows pathways for synthesis, recycling, and assimilatio