As a leading CRO company, Creative Biolabs is devoted to helping global clients to explore and identify the potential and well-recognized targets for antifungal drug development. Here we describe the attractive antifungal targets involved in the phospholipid biosynthesis.
Introduction of Phospholipid
Fungi cell membrane is rich in a variety of lipids belonging to the class glycerophospholipids, sphingolipids, and sterols. Glycerophospholipids consist of glyc-erol-3-phosphate that contains two fatty acyl chains along with various substituents like choline, serine, and ethano-lamine. Various phospholipids have been detected including phosphatidic acid, phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylglycerol (PG), phosphatidylinositol (PI), cardiolipin and sphingolipids such as inositol phosphateceramide, mannosyl-inositolphosphate-ceramide, and mannosyl-diinositolphosphate-ceramide in the cell membrane of Saccharomyces cerevisiae.
Phospholipid Biosynthesis
Phospholipid biosynthesis pathways in fungi include endogenous and exogenous pathways. In almost all endogenous pathways, all membrane phospholipids are synthesized via a common liponucleotide precursor called CDP-diacylglycerol (GDP-DAG). PS is synthesized via PS synthase by catalyzing the reaction between CDP-DAG and serine, whereas PE and serine are converted to PS by the enzyme PS synthase II in other organisms. Therefore targeting fungal PS synthase would be a promising approach for antifungal drug development. Besides, some key enzymes specific to fungi in phospholipid biosynthesis also become the targets of antifungal drug development, such as PS decarboxylase and PE N-methyl-transferase.
Fig.1 Enzymes and respective inhibitors for phospholipid biosynthesis. (Sant, 2016)
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Reference
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