Abstract:NAD(P) is an indispensable cofactor for all organisms and its biosynthetic pathways are proposed as promising novel antibiotics targets against pathogens such as Mycobacterium tuberculosis. Six NAD(P) biosynthetic pathways were reconstructed by comparative genomics: de novo pathway (Asp), de novo pathway (Try), NmR pathway I (RNK-dependent), NmR pathway II (RNK-independent), Niacin salvage, and Niacin recycling. Three enzymes pivotal to the key reactions of NAD(P) biosynthesis are shared by almost all organism… Show more
“…Transferring electrons from one metabolite to another, the coenzyme participates in numerous metabolic redox reactions (Belenky et al 2007;Pollak et al 2007). Additionally, some NAD + is converted into the coenzyme nicotinamide adenine dinucleotide phosphate (NADP NAD synthetase, catalyzing a two-step reaction that transforms deamido-NAD into NAD, is an essential enzyme involved in both the de novo biosynthesis and salvage of NAD + (Bi et al 2011;Magni et al 2009). Phytoplasma genomes lack a gene encoding a canonical NH 3 / glutamine-dependent NAD synthetase such as is present in all known bacteria with walls and in cell wall-less bacteria including mycoplasmas and spiroplasmas.…”
Section: Phytoplasma Genomes and Redox Homeostasismentioning
“…Transferring electrons from one metabolite to another, the coenzyme participates in numerous metabolic redox reactions (Belenky et al 2007;Pollak et al 2007). Additionally, some NAD + is converted into the coenzyme nicotinamide adenine dinucleotide phosphate (NADP NAD synthetase, catalyzing a two-step reaction that transforms deamido-NAD into NAD, is an essential enzyme involved in both the de novo biosynthesis and salvage of NAD + (Bi et al 2011;Magni et al 2009). Phytoplasma genomes lack a gene encoding a canonical NH 3 / glutamine-dependent NAD synthetase such as is present in all known bacteria with walls and in cell wall-less bacteria including mycoplasmas and spiroplasmas.…”
Section: Phytoplasma Genomes and Redox Homeostasismentioning
“…These enzymes are encoded by the conserved genes pncB , nadD and nadE , respectively. Enzymes involved in NAD biosynthesis have been considered as promising drug targets because they are essential for the viability of most bacteria [23, 24]; however, only nadE is annotated in M. hyopneumoniae . Because NadD is likely essential, characterization of this enzyme using a structure-based approach for M. hyopneumoniae will improve its annotation and add this enzyme to the list of potential therapeutic targets.Fig.…”
Enzootic pneumonia caused by Mycoplasma hyopneumoniae is a major constraint to efficient pork production throughout the world. This pathogen has a small genome with 716 coding sequences, of which 418 are homologous to proteins with known functions. However, almost 42% of the 716 coding sequences are annotated as hypothetical proteins. Alternative methodologies such as threading and comparative modeling can be used to predict structures and functions of such hypothetical proteins. Often, these alternative methods can answer questions about the properties of a model system faster than experiments. In this study, we predicted the structures of seven proteins annotated as hypothetical in M. hyopneumoniae, using the structure-based approaches mentioned above. Three proteins were predicted to be involved in metabolic processes, two proteins in transcription and two proteins where no function could be assigned. However, the modeled structures of the last two proteins suggested experimental designs to identify their functions. Our findings are important in diminishing the gap between the lack of annotation of important metabolic pathways and the great number of hypothetical proteins in the M. hyopneumoniae genome.
“…In the NAD + synthesis pathways, several variations exist and multiple enzymes are involved [161,164]. In contrast, NADK is the sole enzyme able to generate NADP + de novo.…”
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