Microbial Metabolites As Antifungal Leads

The merits of natural products as fungicides can be a disadvantage in some respects. Their specific activity often resulted in a narrow antifungal spectrum with a limited application and the development of resistance strains under high selection pressure. Their biodegradability can also make them fragile, which results in short residual activity under harsh field conditions. These might be the reasons why the microbial metabolites used as commercial fungicide per se still commands less than 1% of total fungicide market (Tanaka and Omura 1993). Recently, a breakthrough in biofungicide research came from the semisynthetic approach using microbial metabolites as lead compounds. In particular, a far more promising and effective strategy for the development of new biofungicides is to use knowledge of the structure of antifungal compounds as the starting point for the synthesis of the compounds with optimized physical, biological, and environmental properties. The activity of natural products can in principle be improved by chemical modification. However, this approach relies heavily on the ready availability of sufficient quantities of the natural starting materials and the development of appropriate synthetic methodology. The biofungicides that were developed in this way are fenpiclonil and fludioxonil (Nyfeler and Ackermann 1992) and synthetic derivatives of antibiotic strobilurins such as b-methoxyacrylate azoxystrobin and kresoxim-methyl (Anke et al. 1977; Godfrey 1994). Such a derivative synthesized from microbial metabolites not only enhanced control efficacy but also improved properties such as photochemical stability, low cytotoxicity, and phyto-toxicity. These successes encouraged the fungicide researchers to search versatile lead compounds from diverse microbial sources with novel mode of action.

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