Abstract

Aflatoxins and melanins are the products of a polyketide biosynthesis. In this study, the search of potential inhibitors of the aflatoxin B1 (AFB1) biosynthesis was performed among compounds blocking the pigmentation in fungi. Four compounds—three natural (thymol, 3-hydroxybenzaldehyde, compactin) and one synthetic (fluconazole)—were examined for their ability to block the pigmentation and AFB1 production in Aspergillus flavus. All compounds inhibited the mycelium pigmentation of a fungus growing on solid medium. At the same time, thymol, fluconazole, and 3-hydroxybenzaldehyde stimulated AFB1 accumulation in culture broth of A. flavus under submerged fermentation, whereas the addition of 2.5 μg/mL of compactin resulted in a 50× reduction in AFB1 production. Moreover, compactin also suppressed the sporulation of A. flavus on solid medium. In vivo treatment of corn and wheat grain with compactin (50 μg/g of grain) reduced the level of AFB1 accumulation 14 and 15 times, respectively. Further prospects of the compactin study as potential AFB1 inhibitor are discussed.

Highlights

  • Fungal polyketides represent a large group of biologically active compounds synthesized by enzymes from the polyketide synthase (PKS) family [1]

  • It is known that the fungicide action of triazoles is determined by their ability to inhibit the biosynthesis of sterols [18]. We showed that this fungicide was able to depigment the colonies of some fungi including A. flavus, so we supposed it could influence on toxinogenesis

  • Based on the above-described considerations, the purpose of this study was the examination of four compounds of different nature (Figure 1) for their effect on both aflatoxin B1 (AFB1) and melanin production to find compound(s) able to block the early stages of polyketide biosynthesis, as well as the in vivo evaluation

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Summary

Introduction

Fungal polyketides represent a large group of biologically active compounds synthesized by enzymes from the polyketide synthase (PKS) family [1]. Aflatoxins are secondary metabolites produced by Aspergillus flavus via the polyketide pathway. The ability to produce aflatoxins is probably not related to the essential features of A. flavus, but may give some competitive advantages to this fungus compared with other toxin-sensitive microorganisms [2,3]. A highly hepatotoxic and carcinogenic aflatoxin B1 (AFB1) is of greatest concern because it can contaminate a wide range of agricultural products that results in great losses in agricultural income and has a significant negative economic impact. A number of methods are developed for pre- and post-harvest aflatoxin management [4]. Traditional approaches, such as fungicides, have shown very limited success in the AFB1 control [5]

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