Home LiteratureArticle Details
PMID: 18276644 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Transcriptional regulation of NAD metabolism in bacteria: genomic reconstruction of NiaR (YrxA) regulon.

Nucleic acids research ·Vol. 36 ·No. 6 ·2008-04-00 ·Pages 2032-46

Rodionov DA, Li X, Rodionova IA, Yang C, Sorci L, Dervyn E, Martynowski D, Zhang H, Gelfand MS, Osterman AL

Abstract

A comparative genomic approach was used to reconstruct transcriptional regulation of NAD biosynthesis in bacteria containing orthologs of Bacillus subtilis gene yrxA, a previously identified niacin-responsive repressor of NAD de novo synthesis. Members of YrxA family (re-named here NiaR) are broadly conserved in the Bacillus/Clostridium group and in the deeply branching Fusobacteria and Thermotogales lineages. We analyzed upstream regions of genes associated with NAD biosynthesis to identify candidate NiaR-binding DNA motifs and assess the NiaR regulon content in these species. Representatives of the two distinct types of candidate NiaR-binding sites, characteristic of the Firmicutes and Thermotogales, were verified by an electrophoretic mobility shift assay. In addition to transcriptional control of the nadABC genes, the NiaR regulon in some species extends to niacin salvage (the pncAB genes) and includes uncharacterized membrane proteins possibly involved in niacin transport. The involvement in niacin uptake proposed for one of these proteins (re-named NiaP), encoded by the B. subtilis gene yceI, was experimentally verified. In addition to bacteria, members of the NiaP family are conserved in multicellular eukaryotes, including human, pointing to possible NaiP involvement in niacin utilization in these organisms. Overall, the analysis of the NiaR and NrtR regulons (described in the accompanying paper) revealed mechanisms of transcriptional regulation of NAD metabolism in nearly a hundred diverse bacteria.

MeSH Terms
Bacillus subtilis/genetics,metabolism Bacterial Proteins/classification,genetics,metabolism Binding Sites Gene Expression Regulation, Bacterial Genome, Bacterial Genomics Membrane Transport Proteins/classification,genetics NAD/metabolism Niacin/metabolism Regulatory Elements, Transcriptional Regulon Repressor Proteins/classification,genetics,metabolism Thermotoga maritima/genetics Transcription, Genetic
Chemicals
Bacterial Proteins Membrane Transport Proteins Repressor Proteins NAD Niacin
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Rodionov Dmitry A
Burnham Institute for Medical Research, La Jolla, CA 92037, USA. rodionov@burnham.org
Li Xiaoqing
Rodionova Irina A
Yang Chen
Sorci Leonardo
Dervyn Etienne
Martynowski Dariusz
Zhang Hong
Gelfand Mikhail S
Osterman Andrei L
References (56)
56 references, click to expand
  1. The biosynthesis of nicotinamide adenine dinucleotides in bacteria.
    Vitam Horm. 2001;61:103-19 PMID: 11153263
  2. A subsystems-based approach to the identification of drug targets in bacterial pathogens.
    Prog Drug Res. 2007;64:131, 133-70 PMID: 17195474
  3. Cloning, nucleotide sequence, and regulation of the Bacillus subtilis nadB gene and a nifS-like gene, both of which are essential for NAD biosynthesis.
    J Bacteriol. 1993 Mar;175(5):1423-32 PMID: 8444804
  4. Prediction of transcription regulatory sites in Archaea by a comparative genomic approach.
    Nucleic Acids Res. 2000 Feb 1;28(3):695-705 PMID: 10637320
  5. Mechanism and regulation of human intestinal niacin uptake.
    Am J Physiol Cell Physiol. 2005 Jul;289(1):C97-103 PMID: 15728713
  6. Crystal structure of a transcription regulator (TM1602) from Thermotoga maritima at 2.3 A resolution.
    Proteins. 2007 Apr 1;67(1):247-52 PMID: 17256761
  7. Transcriptional regulation of the Saccharomyces cerevisiae DAL5 gene family and identification of the high affinity nicotinic acid permease TNA1 (YGR260w).
    FEBS Lett. 2000 Jun 23;475(3):237-41 PMID: 10869563
  8. The use of gene clusters to infer functional coupling.
    Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2896-901 PMID: 10077608
  9. SVOP, an evolutionarily conserved synaptic vesicle protein, suggests novel transport functions of synaptic vesicles.
    J Neurosci. 1998 Nov 15;18(22):9269-81 PMID: 9801366
  10. The subsystems approach to genome annotation and its use in the project to annotate 1000 genomes.
    Nucleic Acids Res. 2005 Oct 07;33(17):5691-702 PMID: 16214803
  11. Enzymology of NAD+ synthesis.
    Adv Enzymol Relat Areas Mol Biol. 1999;73:135-82, xi PMID: 10218108
  12. Structural genomics of the Thermotoga maritima proteome implemented in a high-throughput structure determination pipeline.
    Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11664-9 PMID: 12193646
  13. Evolution of the NadR regulon in Enterobacteriaceae.
    J Bioinform Comput Biol. 2005 Aug;3(4):1007-19 PMID: 16078372
  14. New functions of a long-known molecule. Emerging roles of NAD in cellular signaling.
    Eur J Biochem. 2000 Mar;267(6):1550-64 PMID: 10712584
  15. A vector for systematic gene inactivation in Bacillus subtilis.
    Microbiology (Reading). 1998 Nov;144 ( Pt 11):3097-3104 PMID: 9846745
  16. YrxA is the transcriptional regulator that represses de novo NAD biosynthesis in Bacillus subtilis.
    J Bacteriol. 2005 Oct;187(20):7155-60 PMID: 16199587
  17. EnteriX 2003: Visualization tools for genome alignments of Enterobacteriaceae.
    Nucleic Acids Res. 2003 Jul 1;31(13):3527-32 PMID: 12824359
  18. Ribosylnicotinamide kinase domain of NadR protein: identification and implications in NAD biosynthesis.
    J Bacteriol. 2002 Dec;184(24):6906-17 PMID: 12446641
  19. Transcriptional regulation of NAD metabolism in bacteria: NrtR family of Nudix-related regulators.
    Nucleic Acids Res. 2008 Apr;36(6):2047-59 PMID: 18276643
  20. PcaK, a high-affinity permease for the aromatic compounds 4-hydroxybenzoate and protocatechuate from Pseudomonas putida.
    J Bacteriol. 1997 Aug;179(16):5056-61 PMID: 9260946
  21. Recognition of regulatory sites by genomic comparison.
    Res Microbiol. 1999 Nov-Dec;150(9-10):755-71 PMID: 10673013
  22. The Escherichia coli NadR regulator is endowed with nicotinamide mononucleotide adenylyltransferase activity.
    J Bacteriol. 1999 Sep;181(17):5509-11 PMID: 10464228
  23. Comparative genomic reconstruction of transcriptional regulatory networks in bacteria.
    Chem Rev. 2007 Aug;107(8):3467-97 PMID: 17636889
  24. Metabolism of 6-aminonicotinic acid in Escherichia coli.
    J Bacteriol. 1977 Sep;131(3):789-94 PMID: 19420
  25. Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection.
    Mol Syst Biol. 2006;2:2006.0008 PMID: 16738554
  26. Aspartate dehydrogenase, a novel enzyme identified from structural and functional studies of TM1643.
    J Biol Chem. 2003 Mar 7;278(10):8804-8 PMID: 12496312
  27. Crystal structure of Haemophilus influenzae NadR protein. A bifunctional enzyme endowed with NMN adenyltransferase and ribosylnicotinimide kinase activities.
    J Biol Chem. 2002 Sep 6;277(36):33291-9 PMID: 12068016
  28. Mechanism of nicotinic acid transport in human liver cells: experiments with HepG2 cells and primary hepatocytes.
    Am J Physiol Cell Physiol. 2007 Dec;293(6):C1773-8 PMID: 17928533
  29. NAD-dependent DNA-binding activity of the bifunctional NadR regulator of Salmonella typhimurium.
    J Bacteriol. 1999 Jan;181(2):648-55 PMID: 9882682
  30. Inferring phylogenies from protein sequences by parsimony, distance, and likelihood methods.
    Methods Enzymol. 1996;266:418-27 PMID: 8743697
  31. GenBank.
    Nucleic Acids Res. 2007 Jan;35(Database issue):D21-5 PMID: 17202161
  32. Domain organization and a protease-sensitive loop in eukaryotic ornithine decarboxylase.
    Biochemistry. 1995 Oct 17;34(41):13431-6 PMID: 7577930
  33. Multiple sequence alignment with the Clustal series of programs.
    Nucleic Acids Res. 2003 Jul 1;31(13):3497-500 PMID: 12824352
  34. Structure and chemistry of the Sir2 family of NAD+-dependent histone/protein deactylases.
    Biochem Soc Trans. 2004 Dec;32(Pt 6):904-9 PMID: 15506920
  35. Bacterial DNA ligases.
    Mol Microbiol. 2001 Jun;40(6):1241-8 PMID: 11442824
  36. Computer analysis of transcription regulatory patterns in completely sequenced bacterial genomes.
    Nucleic Acids Res. 1999 Jul 15;27(14):2981-9 PMID: 10390542
  37. Molecular biology of pyridine nucleotide and nicotine biosynthesis.
    Front Biosci. 2004 May 01;9:1577-86 PMID: 14977569
  38. [Software for analyzing bacterial genomes].
    Mol Biol (Mosk). 2000 Mar-Apr;34(2):253-62 PMID: 10779952
  39. Identification of a bacterial regulatory system for ribonucleotide reductases by phylogenetic profiling.
    Trends Genet. 2005 Jul;21(7):385-9 PMID: 15949864
  40. How gene order is influenced by the biophysics of transcription regulation.
    Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):13948-53 PMID: 17709750
  41. Overcoming expression and purification problems of RhoGDI using a family of "parallel" expression vectors.
    Protein Expr Purif. 1999 Feb;15(1):34-9 PMID: 10024467
  42. WebLogo: a sequence logo generator.
    Genome Res. 2004 Jun;14(6):1188-90 PMID: 15173120
  43. Pfam: clans, web tools and services.
    Nucleic Acids Res. 2006 Jan 1;34(Database issue):D247-51 PMID: 16381856
  44. NAD+ metabolism in health and disease.
    Trends Biochem Sci. 2007 Jan;32(1):12-9 PMID: 17161604
  45. Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization.
    J Biol Chem. 1999 May 21;274(21):14875-83 PMID: 10329687
  46. Major facilitator superfamily.
    Microbiol Mol Biol Rev. 1998 Mar;62(1):1-34 PMID: 9529885
  47. benK encodes a hydrophobic permease-like protein involved in benzoate degradation by Acinetobacter sp. strain ADP1.
    J Bacteriol. 1997 Sep;179(18):5943-6 PMID: 9294456
  48. 6-Aminonicotinamide-resistant mutants of Salmonella typhimurium.
    J Bacteriol. 1983 Jun;154(3):1126-36 PMID: 6222034
  49. The COG database: a tool for genome-scale analysis of protein functions and evolution.
    Nucleic Acids Res. 2000 Jan 1;28(1):33-6 PMID: 10592175
  50. Regulation of NAD synthesis by the trifunctional NadR protein of Salmonella enterica.
    J Bacteriol. 2005 Apr;187(8):2774-82 PMID: 15805524
  51. Regulatory potential, phyletic distribution and evolution of ancient, intracellular small-molecule-binding domains.
    J Mol Biol. 2001 Apr 13;307(5):1271-92 PMID: 11292341
  52. Conservation of the binding site for the arginine repressor in all bacterial lineages.
    Genome Biol. 2001;2(4):RESEARCH0013 PMID: 11305941
  53. Analysis of genomic context: prediction of functional associations from conserved bidirectionally transcribed gene pairs.
    Nat Biotechnol. 2004 Jul;22(7):911-7 PMID: 15229555
  54. Comparative genomics of NAD biosynthesis in cyanobacteria.
    J Bacteriol. 2006 Apr;188(8):3012-23 PMID: 16585762
  55. Nicotinic acid transport in Escherichia coli.
    Microbios. 1985;44(179-180):169-84 PMID: 2939322
  56. Transport of B-vitamins in microorganisms. VII. The uptake of 14 C-niacinamide by non-proliferating cells and by protoplasts of Streptococcus faecalis.
    Acta Chem Scand. 1966;20(6):1529-34 PMID: 4226091
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkn046
Email
rodionov@burnham.org
Published
2008-04-00
Epub
2008-00-14
Pages
2032-46
Language
English
Region
England
NLM ID
0411011
PMCID
PMC2330245
Subset
IM
Grants
NIAID NIH HHS · R01 AI066244 · United States
NIAID NIH HHS · 1-R01-AI066244-01A2 · United States
External Links
PubMed source DOI: 10.1093/nar/gkn046 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2