Sterol Biosynthesis

The biosynthesis of sterols is an essential metabolism that produce essential constituents of cellular membranes. Most of fungi contain ergosterol as a predominant sterol (Mercer 1991). Recent advances in our understanding of mode of action of sterol biosynthesis inhibitors (SBI) launched a novel approach to finding inhibitors of sterol biosynthesis, which could lead to new agricultural fungicides (Barrett-Bee and Ryder 1992). The antifungal effects of SBI have brought out a great commercial success in the synthetic fungicide market. The SBI fungicides covering about the half of the market is now practically applied to protect fruits, vegetables, and vines from plant diseases. The major SBI are the inhibitors of 14-demethylation which correspond to many antifungal compounds, referred to as azole compounds, with a wide spectrum of intrinsic activity against ascomycete, basidio-mycete and deuteromycete pathogens (Aoki et al. 1993).

The discovery of restricticins and lanomycin led to the introduction of a new target for screening of the antifungal natural products. The two structurally related compounds were first isolated from the cultures of Penicillium restrictum (Schwartz et al. 1991) and Pycnidiophora dispersa (O'Sullivan et al. 1992), respectively (Figure 2). Both restricticin and lanomycin showed potent antifungal activity through inhibition of lanosterol C14-demethylase, one of the main steps in ergosterol biosynthesis. It is interesting to note that the structure of restricticin does not have a (phenylethyl)triazole moiety found in all azole antifungal agents in the market, possibly causing adverse impacts in efficacy and resistance (Tuite 1996). However, restricticin needed to be improved in its chemical stability, because the compound was found to be unstable due to the lability of the glycin ester side chain toward base-mediated hydrolysis and the tendency of the triene functionality to undergo decomposition (Barrett-Bee and Ryder 1992). Along with the advances in the screening for inhibitors of other steps in sterol biosynthesis, more SBI sufficient for practical uses may be discovered from microbial metabolites.

Making Your Own Wine

Making Your Own Wine

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