Microbial NAD Metabolism: Lessons from Comparative Genomics |
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Authors: | Francesca Gazzaniga Rebecca Stebbins Sheila Z Chang Mark A McPeek Charles Brenner |
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Institution: | Departments of Genetics and Biochemistry and Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, New Hampshire 03756,1. Department of Biological Sciences, Dartmouth College, Hanover, New Hampshire, 03755,2. Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 522423. |
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Abstract: | Summary: NAD is a coenzyme for redox reactions and a substrate of NAD-consuming enzymes, including ADP-ribose transferases, Sir2-related protein lysine deacetylases, and bacterial DNA ligases. Microorganisms that synthesize NAD from as few as one to as many as five of the six identified biosynthetic precursors have been identified. De novo NAD synthesis from aspartate or tryptophan is neither universal nor strictly aerobic. Salvage NAD synthesis from nicotinamide, nicotinic acid, nicotinamide riboside, and nicotinic acid riboside occurs via modules of different genes. Nicotinamide salvage genes nadV and pncA, found in distinct bacteria, appear to have spread throughout the tree of life via horizontal gene transfer. Biochemical, genetic, and genomic analyses have advanced to the point at which the precursors and pathways utilized by a microorganism can be predicted. Challenges remain in dissecting regulation of pathways. |
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