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Comparative genomics of NAD(P) biosynthesis and novel antibiotic drug targets
Author(s) -
Bi Jicai,
Wang Honghai,
Xie Jianping
Publication year - 2011
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22419
Subject(s) - nad+ kinase , biosynthesis , cofactor , niacin , biochemistry , mycobacterium tuberculosis , enzyme , biology , metabolic pathway , antibiotics , chemistry , tuberculosis , medicine , pathology
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 organisms, that is, NMN/NaMN adenylyltransferase (NMN/NaMNAT), NAD synthetase (NADS), and NAD kinase (NADK). They might serve as ideal broad spectrum antibiotic targets. Studies in M. tuberculosis have in part tested such hypothesis. Three regulatory factors NadR, NiaR, and NrtR, which regulate NAD biosynthesis, have been identified. M. tuberculosis NAD(P) metabolism and regulation thereof, potential drug targets and drug development are summarized in this paper. J. Cell. Physiol. 226: 331–340, 2011. © 2010 Wiley‐Liss, Inc.