ArticleThe Journal of biological chemistry2010
Genomics-driven reconstruction of acinetobacter NAD metabolism: insights for antibacterial target selection.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 46 citations in OpenAlex.
- Regulation of NADPathogens (Basel, Switzerland) · 2025Article
- Enhancing production of nicotinamide mononucleotide by metabolic engineering and flow cytometry screening of Escherichia coli.Biotechnology letters · 2025Article
- In silico studies on nicotinamide analogs as competitive inhibitors of nicotinamidase in methicillin-resistant Staphylococcus aureus.Molecular diversity · 2025Article
- Enhancing cellulase biosynthesis ofiScience · 2025Article
- Structural insights into Xanthomonas campestris pv. campestris NADCommunications biology · 2024Article
- Engineering nonphotosynthetic carbon fixation for production of bioplastics by methanogenic archaea.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Effect of Divalent Metal Ion on the Structure, Stability and Function ofInternational journal of molecular sciences · 2021Article
- Metabolic engineering of Escherichia coli for biosynthesis of β-nicotinamide mononucleotide from nicotinamide.Microbial biotechnology · 2021Article
- Genome-Scale Metabolic Modeling Reveals Metabolic Alterations of Multidrug-ResistantMicroorganisms · 2020Article
- Toward a structome of Acinetobacter baumannii drug targets.Protein science : a publication of the Protein Society · 2020Article
- The Prospective Synergy of Antitubercular Drugs With NAD Biosynthesis Inhibitors.Frontiers in microbiology · 2020Review
- Extracellular nicotinate phosphoribosyltransferase binds Toll like receptor 4 and mediates inflammation.Nature communications · 2019Article
- Identification of evolutionary and kinetic drivers of NAD-dependent signaling.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Responses of Acinetobacter baumannii Bound and Loose Extracellular Polymeric Substances to Hyperosmotic Agents Combined with or without Tobramycin: An Atomic Force Microscopy Study.Langmuir : the ACS journal of surfaces and colloids · 2019Article
- Novel Antimycobacterial Compounds Suppress NAD Biogenesis by Targeting a Unique Pocket of NaMN Adenylyltransferase.ACS chemical biology · 2019Article
- Modular engineering to increase intracellular NAD(H/Nature communications · 2018Article
- Article
- Mycobacterial nicotinate mononucleotide adenylyltransferase: structure, mechanism, and implications for drug discovery.The Journal of biological chemistry · 2015Article
- Metabolic and bactericidal effects of targeted suppression of NadD and NadE enzymes in mycobacteria.mBio · 2014Article
- Explaining microbial phenotypes on a genomic scale: GWAS for microbes.Briefings in functional genomics · 2013Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Enzymes involved in the last steps of NAD biogenesis, nicotinate mononucleotide adenylyltransferase (NadD) and NAD synthetase (NadE), are conserved and essential in most bacterial species and are established targets for antibacterial drug development. Our genomics-based reconstruction of NAD metabolism in the emerging pathogen Acinetobacter baumannii revealed unique features suggesting an alternative targeting strategy. Indeed, genomes of all analyzed Acinetobacter species do not encode NadD, which is functionally replaced by its distant homolog NadM. We combined bioinformatics with genetic and biochemical techniques to elucidate this and other important features of Acinetobacter NAD metabolism using a model (nonpathogenic) strain Acinetobacter baylyi sp. ADP1. Thus, a comparative kinetic characterization of PncA, PncB, and NadV enzymes allowed us to suggest distinct physiological roles for the two alternative, deamidating and nondeamidating, routes of nicotinamide salvage/recycling. The role of the NiaP transporter in both nicotinate and nicotinamide salvage was confirmed. The nondeamidating route was shown to be transcriptionally regulated by an ADP-ribose-responsive repressor NrtR. The NadM enzyme was shown to possess dual substrate specificity toward both nicotinate and nicotinamide mononucleotide substrates, which is consistent with its essential role in all three routes of NAD biogenesis, de novo synthesis as well as the two salvage pathways. The experimentally confirmed unconditional essentiality of nadM provided support for the choice of the respective enzyme as a drug target. In contrast, nadE, encoding a glutamine-dependent NAD synthetase, proved to be dispensable when the nondeamidating salvage pathway functioned as the only route of NAD biogenesis.
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