Fungal homoserine transacetylase: A potential antifungal target

We are facing a significant challenge due to the tremendous rise in drug resistant fungal pathogen populations. The number of antifungal drugs is limited, as are the known targets they inhibit. The limited number of drugs and targets that have been successfully exploited in antifungal drug discovery is in part due to the eukaryotic nature of these organisms, which is shared with mammalian cells. An ideal antifungal substance is one that targets an indispensable pathway for pathogenic fungal survival that is not present in mammals or plants. Methionine is an essential amino acid for fungi and inhibition of its biosynthesis is deleterious for the pathogen. The biochemical pathways that produce methionine do not exist in mammals as they acquire it from their diet. Homoserine transacetylase, which catalyses the first committed step in methionine biosynthesis, therefore represents an attractive drug target. This enzyme is absent in mammals and unique to fungi and bacteria, suggesting that drugs targeting it would be of low toxicity, if any, to mammals, while having a lethal effect against the fungal pathogen. Homoserine transacetylase, based on its role in the production of methionine and its absence in mammals and plants could be a potential antifungal target.