Ubiquinone and menaquinone in bacteria: A comparative study of some bacterial respiratory systems

Pandya, K. P.; King, H. K.

doi:10.1016/0003-9861(66)90316-x

Cited by 20 publications

(14 citation statements)

References 13 publications

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“…(a) Structure of mycobacterial lipoquinones-The lipoquinones involved in the respiratory chains of bacteria consist of menaquinones and ubiquinones [95], while mammals have only ubiquinone. Menaquinones (2-methyl-3-polyprenyl-1,4naphthoquinones) are the predominant isoprenoid lipoquinones of mycobacteria and many Gram-positive bacteria, whereas Gram-negative bacteria typically utilize both menaquinone and ubiquinone or ubiquinone (which has a benzoquinone ring rather than a napthoquinone ring) solely [96][97][98][99][100].…”

Section: Menaquinonesmentioning

confidence: 99%

Genetics of Capsular Polysaccharides and Cell Envelope (Glyco)lipids

Daffé

Crick

Jackson

2015

Molecular Genetics of Mycobacteria

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This chapter summarizes what is currently known of the structures, physiological roles, involvement in pathogenicity and biogenesis of a variety of non-covalently bound cell envelope lipids and glycoconjugates of Mycobacterium tuberculosis and other Mycobacterium species. Topics addressed in this chapter include phospholipids; phosphatidylinositol mannosides; triglycerides; isoprenoids and related compounds (polyprenyl phosphate, menaquinones, carotenoids, non-carotenoid cyclic isoprenoids); acyltrehaloses (lipooligosaccharides, trehalose mono-and di-mycolates, sulfolipids, di-and poly-acyltrehaloses); mannosyl-beta-1phosphomycoketides; glycopeptidolipids; phthiocerol dimycocerosates, para-hydroxybenzoic acids and phenolic glycolipids; mycobactins; mycolactones; and capsular polysaccharides.

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Section: Menaquinonesmentioning

confidence: 99%

Genetics of Capsular Polysaccharides and Cell Envelope (Glyco)lipids

Daffé

Crick

Jackson

2015

Molecular Genetics of Mycobacteria

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“…Lipoquinones such as ubiquinone (CoQ), phylloquinone, and menaquinone are biological quinones that play pivotal roles in all living organisms [11–16] . CoQ is the primary redox-active electron carrier in the electron transport chain in humans and most aerobically growing Gram-negative bacteria [17, 18] , while phylloquinone plays this role in photosynthetic organisms [19] .…”

Section: Introductionmentioning

confidence: 99%

Mechanism of MenE Inhibition by Acyl-Adenylate Analogues and Discovery of Novel Antibacterial Agents

Matarlo¹,

Evans²,

Sharma³

et al. 2015

Biochemistry

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MenE is an o-succinylbenzoyl-CoA (OSB-CoA) synthetase in the bacterial menaquinone biosynthesis pathway and is a promising target for the development of novel antibacterial agents. The enzyme catalyzes CoA ligation via an acyl-adenylate intermediate, and we have previously reported tight-binding inhibitors of MenE based on stable acyl-sulfonyladenosine analogues of this intermediate, including OSB-AMS (1) which has an IC50 value of ≤ 25 nM for the Escherichia coli MenE. Herein, we show that OSB-AMS reduces menaquinone levels in S. aureus, consistent with its proposed mechanism of action, despite the observation that the antibacterial activity of OSB-AMS is ~1000-fold lower than the IC50 for enzyme inhibition. To inform the synthesis of MenE inhibitors with improved antibacterial activity, we have undertaken a structure–activity relationship (SAR) study stimulated by the knowledge that OSB-AMS can adopt two isomeric forms in which the OSB side chain exists either as an open-chain keto acid or a cyclic lactol. These studies revealed that negatively charged analogues of the keto-acid form bind, while neutral analogues do not, consistent with the hypothesis that the negatively-charged keto-acid form of OSB-AMS is the active isomer. X-ray crystallography and site-directed mutagenesis confirm the importance of a conserved arginine for binding the OSB carboxylate. Although most lactol isomers tested were inactive, a novel difluoroindanediol inhibitor (11) with improved antibacterial activity was discovered, providing a pathway toward the development of optimized MenE inhibitors in the future.

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“…The lipoquinones involved in the respiratory chains of bacteria consist of menaquinones and ubiquinones (Sherman et al ., 1989), while mammals have only ubiquinone. Menaquinones (2‐methyl‐3‐polyprenyl‐1,4‐naphthoquinones) are the predominant lipoquinones of mycobacteria and other Gram‐positive bacteria , whereas Gram‐negative bacteria such as E. coli typically utilize both menaquinone and ubiquinone or ubiquinone solely (Pandya and King, 1966; Collins and Jones, 1981; Minnikin, 1982; Embley and Stackebrandt, 1994; Meganathan, 1996).…”

Section: Introductionmentioning

confidence: 99%

Menaquinone synthesis is critical for maintaining mycobacterial viability during exponential growth and recovery from non‐replicating persistence

Dhiman

Mahapatra

Slayden

et al. 2009

Molecular Microbiology

132

149

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Summary Understanding the basis of bacterial persistence in latent infections is critical for eradication of tuberculosis. Analysis of Mycobacterium tuberculosis mRNA expression in an in vitro model of non-replicating persistence indicated that the bacilli require electron transport chain components and ATP synthesis for survival. Additionally, low μM concentrations of aminoalkoxydiphenylmethane derivatives inhibited both the aerobic growth and survival of non-replicating, persistent M. tuberculosis. Metabolic labeling studies and quantitation of cellular menaquinone levels suggested that menaquinone synthesis, and consequently electron transport, is the target of the aminoalkoxydiphenylmethane derivatives. This hypothesis is strongly supported by the observations that treatment with these compounds inhibits oxygen consumption and that supplementation of growth medium with exogenous menaquinone rescued both growth and oxygen consumption of treated bacilli. In vitro assays indicate that the aminoalkoxydiphenylmethane derivatives specifically inhibit MenA, an enzyme involved in the synthesis of menaquinone. Thus, the results provide insight into the physiology of mycobacterial persistence and a basis for the development of novel drugs that enhance eradication of persistent bacilli and latent tuberculosis.

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Ubiquinone and menaquinone in bacteria: A comparative study of some bacterial respiratory systems

Cited by 20 publications

References 13 publications

Genetics of Capsular Polysaccharides and Cell Envelope (Glyco)lipids

Genetics of Capsular Polysaccharides and Cell Envelope (Glyco)lipids

Mechanism of MenE Inhibition by Acyl-Adenylate Analogues and Discovery of Novel Antibacterial Agents

Menaquinone synthesis is critical for maintaining mycobacterial viability during exponential growth and recovery from non‐replicating persistence

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