Journal article

The Metabolite Repair Enzyme Phosphoglycolate Phosphatase Regulates Central Carbon Metabolism and Fosmidomycin Sensitivity in Plasmodium falciparum

Laure Dumont, Mark B Richardson, Phillip van der Peet, Danushka S Marapana, Tony Triglia, Matthew WA Dixon, Alan F Cowman, Spencer J Williams, Leann Tilley, Malcolm J McConville, Simon A Cobbold

mBio | AMER SOC MICROBIOLOGY | Published : 2019

Abstract

Members of the haloacid dehalogenase (HAD) family of metabolite phosphatases play an important role in regulating multiple pathways in Plasmodium falciparum central carbon metabolism. We show that the P. falciparum HAD protein, phosphoglycolate phosphatase (PGP), regulates glycolysis and pentose pathway flux in asexual blood stages via detoxifying the damaged metabolite 4-phosphoerythronate (4-PE). Disruption of the P. falciparumpgp gene caused accumulation of two previously uncharacterized metabolites, 2-phospholactate and 4-PE. 4-PE is a putative side product of the glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase, and its accumulation inhibits the pentose phosphate pathway enzy..

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Grants

Awarded by NHMRC


Awarded by Australian Research Council


Funding Acknowledgements

M.J.M. is an NHMRC Principal Research Fellow. L.T. is an ARC Laureate Professor. This work was supported by NHMRC project grant APP1098992 and Australian Research Council grant DP180102729.