Lipoic Acid Metabolism of Plasmodium - A Suitable Drug Target
LA biosynthesis, comprising octanoyl-acyl carrier protein (ACP) : protein N-octanoyltransferase (LipB) and lipoate synthase (LipA), is exclusively found in the apicoplast of Plasmodium where it generates LA de novo from octanoyl-ACP, provided by the type II fatty acid biosynthesis (FAS II) pathway also present in the organelle. LA is the co-factor of the acetyltransferase subunit of the apicoplast located pyruvate dehydrogenase (PDH), which generates acetyl-CoA, feeding into FAS II. LA biosynthesis is not vital for intra-erythrocytic development of Plasmodium, but the deletion of several genes encoding components of FAS II or PDH was detrimental for liver stage development of the parasites indirectly suggesting that the same applies to LA biosynthesis.
These data provide strong evidence that LA salvage and biosynthesis are vital for different stages of Plasmodium development and offer potential for drug and vaccine design against malaria.
Keywords: Lipoic acid salvage; Plasmodium; apicoplast; chemotherapy; lipoate synthase (LipA); lipoic acid biosynthesis; malaria; octanoyl-acyl carrier protein (ACP); type II fatty acid biosynthesis (FAS II); vaccine development
Document Type: Research Article
Publication date: August 1, 2012
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