2005
DOI: 10.1371/journal.pcbi.0010046.eor
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Flux Balance Analysis of Mycolic Acid Pathway: Targets for Anti-tubercular Drugs

Abstract: Mycobacterium tuberculosis is the focus of several investigations for design of newer drugs, as tuberculosis remains a major epidemic despite the availability of several drugs and a vaccine. Mycobacteria owe many of their unique qualities to mycolic acids, which are known to be important for their growth, survival, and pathogenicity. Mycolic acid biosynthesis has therefore been the focus of a number of biochemical and genetic studies. It also turns out to be the pathway inhibited by front-line anti-tubercular … Show more

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Cited by 19 publications
(20 citation statements)
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“…M. smegmatis does not make cyclopropanated MAs. A recent in silico systematic analysis of MA biosynthesis pathways used flux balance analysis to produce a comprehensive model of MA synthesis in M. tuberculosis (330). This model has yet to be fully investigated in the laboratory.…”
Section: How Do Mycobacteria Synthesize Cell Wall Components?mentioning
confidence: 99%
“…M. smegmatis does not make cyclopropanated MAs. A recent in silico systematic analysis of MA biosynthesis pathways used flux balance analysis to produce a comprehensive model of MA synthesis in M. tuberculosis (330). This model has yet to be fully investigated in the laboratory.…”
Section: How Do Mycobacteria Synthesize Cell Wall Components?mentioning
confidence: 99%
“…These include protein targets involved in cell-wall biosynthesis such as alanine racemase (74); arabinogalactan and LAM biosynthesis pathways (61); and mycolic acid pathway players such as polyketide synthase Pks (75,76), acyl-AMP ligase (77,78), FadD32 (78,79), the AccD4-containing acyl-CoA carboxylase (80), and others. Pathway comparison methods have highlighted a number of enzymes and pathways that are unique to mycobacteria and absent in the host.…”
Section: Currently Explored Targets For Structure-based Anti-tb Drug mentioning
confidence: 99%
“…Patient isolates that are resistant to PZA typically show mutation within the gene encoding PncA (Scorpio & Zhang, 1996). Some weak acids (benzoic, sorbic and propyl hydroxybenzoic acid), UV and various energy inhibitors were found to enhance the activity of PZA in vitro against M. tuberculosis (Wade & Zhang, 2006 (Raman et al, 2005). The MAP model consists of four sub-pathways: (i) production of malonyl CoA, (ii) FAS I pathway, (iii) FAS II pathway and (iv) condensation of FAS I and FAS II products into methoxy-and keto-mycolic acids.…”
Section: Mechanism Of Action Of Pzamentioning
confidence: 99%