Figure 1

Illustration of NAD ⁺ synthetic pathways. A) NAD⁺ de novo synthetic and salvage pathways in Escherichia coli. Dots indicate gene deletions generated by mutagenesis on the pathway. B) Comparison of NAD⁺ synthetic pathways between E. coli that is able to synthesize NAD⁺ via de novo and salvage pathways I and III and pathogenic bacterium Pasteurella multocida that is potentially capable of synthesizing NAD⁺ via salvage pathway II and III. The xapA/PNP-mediated pathway IIIb may enable P. multocida and similar pathogenic bacteria to use NAM as a precursor for NAD⁺ biosynthesis. C) Chemical structures of NAD⁺ and relevant intermediates (R = Ribose sugar, P = Phosphoric acid, Ad = Adenine). Abbreviations of compounds: NA, nicotinic acid; NaAD, nicotinic acid adenine dinucleotide (Deamino-NAD); NAD⁺, nicotinamide adenine dinucleotide; NAM, nicotinamide; NaMN, nicotinic acid mononucleotide; NMN, nicotinamide mononucleotide; NR, nicotinamide riboside; QA, quinolinic acid; Abbreviations of enzymes: nadD, NaMNAT, nicotinic acid mononucleotide adenylyltransferase; nadE, NADS, NAD⁺ synthase; nadF, NAD⁺ kinase; nadR/nadM, nicotinamide-nucleotide adenylyltransferase (NMNAT); NMPRT, nicotinamide phosphoribosyltransferase; NRK, ribosylnicotinamide kinase; pncA, nicotinamidase; pncB, NAPRTase, nicotinic acid phosphoribosyltransferase; pncC, NMN deamidase; nadC, QAPRTase, quinolinic acid phosphoribosyltransferase.