4.1 Article

NAD biosynthesis: Identification of the tryptophan to quinolinate pathway in bacteria

Journal

CHEMISTRY & BIOLOGY
Volume 10, Issue 12, Pages 1195-1204

Publisher

CELL PRESS
DOI: 10.1016/j.chembiol.2003.11.011

Keywords

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Funding

  1. NIDDK NIH HHS [DK44083] Funding Source: Medline
  2. NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK044083, R37DK044083] Funding Source: NIH RePORTER

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Previous studies have demonstrated two different bio-synthetic pathways to quinolinate, the universal de novo precursor to the pyridine ring of NAD. In prokaryotes, quinolinate is formed from aspartate and dihydroxyacetone phosphate; in eukaryotes, it is formed from tryptophan. It has been generally believed that the tryptophan to quinolinic acid biosynthetic pathway is unique to eukaryotes; however, this paper describes the use of comparative genome analysis to identify likely candidates for all five genes involved in the tryptophan to quinolinic acid pathway in several bacteria. Representative examples of each of these genes were overexpressed, and the predicted functions are confirmed in each case using unambiguous biochemical assays.

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