Nucleic Acid Metabolism

One of the areas that can be exploited as antifungal targets is nucleic acid metabolism. The synthesis of nucleic acids involves numerous biochemical reactions ranging from the initial synthesis of purine and pyrimidine precursors to the final polymerization of ribonucleoside and deoxyribonucleo-side 5'-triphosphates into RNA and DNA. A large number of compounds have been known to be inhibitors of nucleic acid metabolism in fungi. However, few of these compounds have been used as agricultural and clinical antifungal agents. Recently, antibiotic tubercidin produced by Streptomyces violaceoniger was discovered to have antifungal activity against plant pathogenic fungi (Hwang and Kim 1995a; Hwang et al. 1994). It was highly active against P. capsici, Botryosphaeria dothidea, and R. solani. Tubercidin is an adenosine analog that interferes nucleic acid synthesis including de novo purine synthesis, rRNA processing, and tRNA methylation (Suhadolnik 1979). The potent in vivo activity of tubercidin against P. capsici was compared with that of systemic fungicide, metalaxyl, which is one of the best-studied acylalanine targeting on the synthesis of ribosomal RNA. Treatment with tubercidin on day 1 before inoculation of zoospores prevented phytophthora blight at 500 mgrnP1. Tubercidin was effective as much as metalaxyl, irrespective of application time and concentrations, although its antifungal activity did not persist as long as metalaxyl in pepper plants. The potent antifungal activity of tubercidin against P. capsici suggests that possible targets for the antifungal agent screening may be present in nucleic acid metabolic pathway.

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