Erratum for the Research Article: “Antimalarial pantothenamide metabolites target acetyl–coenzyme A biosynthesis in Plasmodium falciparum” by J. Schalkwijk, E. L. Allman, P. A. M. Jansen, L. E. de Vries, J. M. J. Verhoef, S. Jackowski, P. N. M. Botman, C. A. Beuckens-Schortinghuis, K. M. J. Koolen, J. M. Bolscher, M. W. Vos, K. Miller, S. A. Reeves, H. Pett, G. Trevitt, S. Wittlin, C. Scheurer, S. Sax, C. Fischli, I. Angulo-Barturen, M. B. Jimenez-Diaz, G. Josling, T. W. A. Kooij, R. Bonnert, B. Campo, R. H. Blaauw, F. P. J. T. Rutjes, R. W. Sauerwein, M. Llinas, P. H. H. Hermkens, K. J. Dechering

2021 ◽  
Vol 13 (580) ◽  
pp. eabg8900
Keyword(s):  
Plasmodium Falciparum ◽  
Coenzyme A ◽  
Acetyl Coenzyme A ◽  
Acetyl Coenzyme ◽  
Research Article ◽  
De Vries ◽  
Coenzyme A Biosynthesis

scholarly journals Antimalarial pantothenamide metabolites target acetyl–coenzyme A biosynthesis in Plasmodium falciparum

2019 ◽  
Vol 11 (510) ◽  
pp. eaas9917 ◽  
Author(s):  
Joost Schalkwijk ◽  
Erik L. Allman ◽  
Patrick A. M. Jansen ◽  
Laura E. de Vries ◽  
Julie M. J. Verhoef ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Coenzyme A ◽  
Mosquito Vector ◽  
Malaria Parasites ◽  
Humanized Mouse Model ◽  
Acetyl Coenzyme A ◽  
Block Transmission ◽  
Acetyl Coenzyme ◽  
Acyl Coenzyme A

Malaria eradication is critically dependent on new therapeutics that target resistant Plasmodium parasites and block transmission of the disease. Here, we report that pantothenamide bioisosteres were active against blood-stage Plasmodium falciparum parasites and also blocked transmission of sexual stages to the mosquito vector. These compounds were resistant to degradation by serum pantetheinases, showed favorable pharmacokinetic properties, and cleared parasites in a humanized mouse model of P. falciparum infection. Metabolomics revealed that coenzyme A biosynthetic enzymes converted pantothenamides into coenzyme A analogs that interfered with parasite acetyl–coenzyme A anabolism. Resistant parasites generated in vitro showed mutations in acetyl–coenzyme A synthetase and acyl–coenzyme A synthetase 11. Introduction and reversion of these mutations in P. falciparum using CRISPR-Cas9 gene editing confirmed the roles of these enzymes in the sensitivity of the malaria parasites to pantothenamides. These pantothenamide compounds with a new mode of action may have potential as drugs against malaria parasites.

Acetyl coenzyme A biosynthesis in the chloroplast

Planta ◽  
1982 ◽  
Vol 156 (1) ◽  
pp. 84-88 ◽  
Author(s):  
Denis J. Murphy ◽  
D. A. Walker
Keyword(s):  
Coenzyme A ◽  
Acetyl Coenzyme A ◽  
Acetyl Coenzyme ◽  
Coenzyme A Biosynthesis

scholarly journals Acetyl Coenzyme A Carboxylase

1969 ◽  
Vol 244 (22) ◽  
pp. 6254-6262 ◽  
Author(s):  
Philip W. Majerus ◽  
Elisabeth Kilburn
Keyword(s):  
Coenzyme A ◽  
Acetyl Coenzyme A ◽  
Acetyl Coenzyme ◽  
Acetyl Coenzyme A Carboxylase
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