Additional remarks phenotype | Mutant/mutation
The mutant lacks expression of PPCDC and expresses GFP under the control of the strong and constitutive hsp70 promoter.
Protein (function)
CoA is an essential cofactor for all prokaryotes and eukaryotes to support a large number of metabolic processes including fatty acid biosynthesis and oxidation, as well as carbohydrate and amino acid metabolism. In many living cells, the transport and utilization of pantothenic acid (vitamin B5, pantothenate in ionic form) is essential for CoA biosynthesis. The cellular machinery for the biosynthesis of CoA from exogenous pantothenate involves a putative pantothenate transporter (PAT) and five enzymes, PanK (Pantothenate Kinase), PPCS (Phosphopantothenylcysteine Synthase), PPCDC (Phosphopantothenylcysteine Decarboxylase), PPAT (Phosphopantetheine Adenylyltransferase), and DPCK (Dephospho-CoA Kinase).
Previous studies showed that PAT, PanK1, and PanK2 genes are dispensable for blood stage development in mice but are crucial for oocyst development and sporozoite formation in the mosquito.
In this study the following was shown: 'The intermediate enzymes PPCS (Phosphopantothenylcysteine Synthase), PPCDC (Phosphopantothenylcysteine Decarboxylase; RMgm-4183) were shown to be dispensable for asexual and sexual blood stage development, but they were essential for oocyst development and the production of sporozoites. However, the last two enzymes of this pathway, PPAT (Phosphopantetheine Adenylyltransferase; RMgm-4184) and DPCK (Dephospho-CoA Kinase; RMgm-4185), were essential for blood stage development. These results indicate alternative first substrate requirement for the malaria parasite, other than the canonical pantothenate, for the synthesis of CoA in the blood but not inside the mosquito midgut. Collectively, these studies indicate that CoA de novo biosynthesis is essential for both blood and mosquito stages'.
Phenotype
Normal blood stage development (including gametocytes). Normal ookinete development/production.Significant reduction in the number of oocysts (already at day 4 after feeding). Reduced size of oocysts. No sporozoite production inside oocyst. No salivary gland sporozoites.
Additional information
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