At present, approximately 200 different fungicides have been introduced into agriculture and horticulture worldwide. Despite the enormous advances in chemical management of fungal diseases, some of the important plant pathogens such as vascular wilt, anthracnoses, take-all of wheat, and other root infections remain uncontrolled by current fungicidal chemicals (Knight et al. 1997). The build-up of resistant strains of target pathogens and the increasing public concern about synthetic fungicides have intensified the need for better and safer compounds in terms of novel modes of action, low rates of use, and low toxicological and environmental risk (Godfrey 1994; Tanaka and Omura 1993). As the environmental and commercial requirements for new fungicides become more demanding, it is increasingly difficult to discover new class of compounds to justify the effort and the costs of development. In order to get a chance to discover new fungicides that meet the mentioned characteristics, the exploitation of biologically active natural products is becoming mainstream in antifungal agent research.

Microbial metabolites represented by antibiotics have a number of chemical and biological merits as fungicides. Microorganisms are capable of synthesizing versatile chemical structures with diverse biological activities beyond the scope of synthetic organic chemistry (Porter 1985). An unexpected and newly found chemical structure is more likely to have new fungicidal activity and mode of action, especially showing no cross-resistance to the commercial fungicides (Friih et al. 1996). Biodegradability is the next property of microbial metabolites that cannot be overlooked. They degrade usually within a month or even a few days, when exposed to agricultural environment, thus leading to the low residual level less harmful to the natural ecosystem (Tanaka and Omura 1993).

Microbial metabolites can be exploited in a number of different ways for the development of new fungicides. They can be directly used as fungicide products or as leads for the design of novel synthetic products. Alternatively, they can be used to highlight novel mode of action available as a new screening target. The recent successes in fungicide development came mainly from the discovery of potent lead compounds followed by chemical modifications that gave additional useful features fungicides. Potent antifungal activity is not the only factor to decide whether the microbial metabolite can be used as a commercial fungicide. Along with the chemical stability in the field, it should also have residual activity enough to reduce the application time to the economical level and low volatibility sufficient to stay on the surface of host plants. Overall, it is very unlikely that a newly discovered microbial metabolite might possess all of the desired properties. Therefore, moving away from the viewpoint of antifungal metabolites as final products, microbial metabolites are currently reexploited as a source of enormously diverse chemical library that can supply lead compounds for development of fungicides. As seen in the example of the successful development of methoxyacrylates that are expected to be a major fungicide class in the future, it is not surprising that natural products are facing a revival as lead compounds for fungicide development.

The advances in molecular, biological, and chemical techniques made it possible to reinvestigate microbial metabolites from a totally different point of view. The increasing knowledge about the complex multidisciplinary mystery of antifungal activity enables us to design a rationalized screening system based on the mode of action. Along with the innovative screening systems, the powerful instruments available for purification and structural elucidation of natural products have made it possible to adopt a high throughput approach to natural product screening (Bindseil et al. 2001).

In this chapter, we will review (a) microbial metabolites currently used as fungicides, (b) on-going efforts to discover lead compounds from diverse microbial sources, and (c) fungal specific targets to be used for screening of potential antifungal leads. In the later part of this review, we will discuss (c) trends in biofungicide research and interdisciplinary approaches to diversify their chemical library, which may yield novel antifungal compounds in the future.

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