Journal article
Nrt1 and Tna1-independent export of NAD+ precursor vitamins promotes NAD+ homeostasis and allows engineering of vitamin production
PloS one, Vol.6(5), e19710
05/11/2011
DOI: 10.1371/journal.pone.0019710
PMCID: PMC3092764
PMID: 21589930
Abstract
NAD(+) is both a co-enzyme for hydride transfer enzymes and a substrate of sirtuins and other NAD(+) consuming enzymes. NAD(+) biosynthesis is required for two different regimens that extend lifespan in yeast. NAD(+) is synthesized from tryptophan and the three vitamin precursors of NAD(+): nicotinic acid, nicotinamide and nicotinamide riboside. Supplementation of yeast cells with NAD(+) precursors increases intracellular NAD(+) levels and extends replicative lifespan. Here we show that both nicotinamide riboside and nicotinic acid are not only vitamins but are also exported metabolites. We found that the deletion of the nicotinamide riboside transporter, Nrt1, leads to increased export of nicotinamide riboside. This discovery was exploited to engineer a strain to produce high levels of extracellular nicotinamide riboside, which was recovered in purified form. We further demonstrate that extracellular nicotinamide is readily converted to extracellular nicotinic acid in a manner that requires intracellular nicotinamidase activity. Like nicotinamide riboside, export of nicotinic acid is elevated by the deletion of the nicotinic acid transporter, Tna1. The data indicate that NAD(+) metabolism has a critical extracellular element in the yeast system and suggest that cells regulate intracellular NAD(+) metabolism by balancing import and export of NAD(+) precursor vitamins.
Details
- Title: Subtitle
- Nrt1 and Tna1-independent export of NAD+ precursor vitamins promotes NAD+ homeostasis and allows engineering of vitamin production
- Creators
- Peter Belenky - Department of Genetics and Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, New Hampshire, United States of AmericaRebecca StebbinsKatrina L BoganCharles R EvansCharles Brenner
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.6(5), e19710
- DOI
- 10.1371/journal.pone.0019710
- PMID
- 21589930
- PMCID
- PMC3092764
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- United States
- Grant note
- DK089503 / NIDDK NIH HHS P30 DK089503 / NIDDK NIH HHS
- Language
- English
- Date published
- 05/11/2011
- Academic Unit
- Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9983788596502771
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