scholarly journals Overcoming synthetic challenges in targeting coenzyme A biosynthesis with the antimicrobial natural product CJ-15,801

MedChemComm ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 2118-2125
Author(s):  
Riyad Domingo ◽  
Renier van der Westhuyzen ◽  
Anton R. Hamann ◽  
Konrad J. Mostert ◽  
Leanne Barnard ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Plasmodium Falciparum ◽  
Natural Product ◽  
Coenzyme A ◽  
Coenzyme A Biosynthesis ◽  
Selective Activity

Presenting an optimised synthesis of the fungus-derived antibiotic CJ-15,801 which shows selective activity against Staphylococcus aureus and Plasmodium falciparum.

Reversal of Multi-Drug Resistance in Staphylococcus aureus by Natural Product-Way Forward

2016 ◽  
Vol 13 (7) ◽  
pp. 668-675
Author(s):  
Saba Farooq ◽  
. Atia-tul-Wahab ◽  
Ali Azarpira ◽  
. Atta-ur-Rahman ◽  
M. Iqbal Choudhary
Keyword(s):  
Staphylococcus Aureus ◽  
Drug Resistance ◽  
Natural Product ◽  
Multi Drug Resistance

A detailed biochemical characterization of phosphopantothenate synthetase, a novel enzyme involved in coenzyme A biosynthesis in the Archaea

Extremophiles ◽  
2012 ◽  
Vol 16 (6) ◽  
pp. 819-828 ◽  
Author(s):  
Takuya Ishibashi ◽  
Hiroya Tomita ◽  
Yuusuke Yokooji ◽  
Tatsuya Morikita ◽  
Bunta Watanabe ◽  
...  
Keyword(s):  
Coenzyme A ◽  
Biochemical Characterization ◽  
Coenzyme A Biosynthesis

Some Aspects of the Enzyme Activities Involved in Coenzyme A Biosynthesis in Various Microorganisms

1974 ◽  
Vol 38 (5) ◽  
pp. 1015-1021 ◽  
Author(s):  
Sakayu Shimizu ◽  
Katsuro Kubo ◽  
Hazime Morioka ◽  
Yoshiki Tani ◽  
Koichi Ogata
Keyword(s):  
Enzyme Activities ◽  
Coenzyme A ◽  
Coenzyme A Biosynthesis

scholarly journals Characterization of Benzoyl Coenzyme A Biosynthesis Genes in the Enterocin-Producing Bacterium “Streptomyces maritimus”

2003 ◽  
Vol 185 (2) ◽  
pp. 399-404 ◽  
Author(s):  
Longkuan Xiang ◽  
Bradley S. Moore
Keyword(s):  
Benzoic Acid ◽  
Phenylalanine Ammonia Lyase ◽  
Coenzyme A ◽  
Primary Metabolism ◽  
The Novel ◽  
Wild Type ◽  
Coa Ligase ◽  
Encoding Gene ◽  
Coenzyme A Biosynthesis

ABSTRACT The novel benzoyl coenzyme A (benzoyl-CoA) biosynthesis pathway in “Streptomyces maritimus” was investigated through a series of target-directed mutations. Genes involved in benzoyl-CoA formation were disrupted through single-crossover homologous recombination, and the resulting mutants were analyzed for their ability to biosynthesize the benzoyl-CoA-primed polyketide antibiotic enterocin. Inactivation of the unique phenylalanine ammonia-lyase-encoding gene encP was previously shown to be absolutely required for benzoyl-CoA formation in “S. maritimus”. The fatty acid β-oxidation-related genes encH, -I, and -J, on the other hand, are necessary but not required. In each case, the yield of benzoyl-CoA-primed enterocin dropped below wild-type levels. We attribute the reduced benzoyl-CoA formation in these specific mutants to functional substitution and cross-talk between the products of genes encH, -I, and -J and the enzyme homologues of primary metabolism. Disruption of the benzoate-CoA ligase encN gene did not perturb enterocin production, however, demonstrating that encN is extraneous and that benzoic acid is not a pathway intermediate. EncN rather serves as a substitute pathway for utilizing exogenous benzoic acid. These experiments provide further support that benzoyl-CoA is formed in a novel bacterial pathway that resembles the eukaryotic assembly of benzoyl-CoA from phenylalanine via a β-oxidative path.

scholarly journals Inhibitors of Pantothenate Kinase: Novel Antibiotics for Staphylococcal Infections

2003 ◽  
Vol 47 (6) ◽  
pp. 2051-2055 ◽  
Author(s):  
Anthony E. Choudhry ◽  
Tracy L. Mandichak ◽  
John P. Broskey ◽  
Richard W. Egolf ◽  
Cynthia Kinsland ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Staphylococcus Aureus ◽  
Biosynthetic Pathway ◽  
Coenzyme A ◽  
Low Molecular Weight ◽  
Pantothenate Kinase ◽  
Staphylococcal Infections ◽  
Low Molecular Weight Compounds ◽  
Novel Antibiotics

ABSTRACT Pantothenate kinase (CoaA) catalyzes the first step of the coenzyme A biosynthetic pathway. Here we report the identification of the Staphylococcus aureus coaA gene and characterization of the enzyme. We have also identified a series of low-molecular-weight compounds which are effective inhibitors of S. aureus CoaA.

scholarly journals A Photoalkylative Fluorogenic Probe of Guttiferone A for Live Cell Imaging and Proteome Labeling in Plasmodium falciparum

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5139
Author(s):  
Romain Duval ◽  
Kevin Cottet ◽  
Magali Blaud ◽  
Anaïs Merckx ◽  
Sandrine Houzé ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Natural Product ◽  
Drug Targets ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Molecular Probe ◽  
Positive Functional ◽  
Fluorogenic Probe ◽  
Symphonia Globulifera

Guttiferone A (GA) 1, a polycyclic polyprenylated acylphloroglucinol (PPAP) isolated from the plant Symphonia globulifera (Clusiaceae), constitutes a novel hit in antimalarial drug discovery. PPAPs do not possess identified biochemical targets in malarial parasites up to now. Towards this aim, we designed and evaluated a natural product-derived photoactivatable probe AZC-GA 5, embedding a photoalkylative fluorogenic motif of the 7-azidocoumarin (AZC) type, devoted to studying the affinity proteins interacting with GA in Plasmodium falciparum. Probe 5 manifested a number of positive functional and biological features, such as (i) inhibitory activity in vitro against P. falciparum blood-stages that was superimposable to that of GA 1, dose–response photoalkylative fluorogenic properties (ii) in model conditions using bovine serum albumin (BSA) as an affinity protein surrogate, (iii) in live P. falciparum-infected erythrocytes, and (iv) in fresh P. falciparum cell lysate. Fluorogenic signals by photoactivated AZC-GA 5 in biological settings were markedly abolished in the presence of excess GA 1 as a competitor, indicating significant pharmacological specificity of the designed molecular probe relative to the native PPAP. These results open the way to identify the detected plasmodial proteins as putative drug targets for the natural product 1 by means of proteomic analysis.

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