Cloning and Characterization of Geotrichum candidum Histidinol Dehydrogenase: A New Antifungal Target

Enzymes of essential amino acid biosynthesis pathways are the targets of choice for drug discovery as these pathways are absent in mammals. Inhibitors of these enzymes will have reduced toxicity problems for the vertebrate host organisms. The histidine biosynthesis pathway is an important biochemical pathway found in bacteria, archebacteria, fungi and plants but absent in human. In recent times this enzyme has been exploited to develop target specific antibacterial against B. suis. In a bid to identify antigfungal agents targeted against histidinol dehydrogenase; we have cloned, sequenced and characterized histidinol dehydrogenase gene from Geotrichum candidum. Biochemical characterization was done to establish inhibitor-screening assay. Using this assay D-histidine was identified as potent inhibitor of Geotrichum candidum histidinol dehydrogenase and growth at 10.8 μM and 173.7 μM concentrations respectively. This assay can further be exploited to screen novel antifungal agents.