天然产物抑制黄曲霉生长及其产毒的研究进展

Research progress of natural products’ inhibition on the growth and aflatoxin synthesis of Aspergillus flavus

黄曲霉是一种腐生丝状致病真菌,广泛存在于储藏粮食及加工食品中,其产生的次级代谢物——黄曲霉毒素已被列为一级致癌物,不仅给我国的粮食出口造成了巨大的经济损失,而且严重危害人体健康。天然产物是取自植物和微生物的组分或次级代谢物,其中有许多是抑制黄曲霉生长及产毒的高效、安全化合物。结合国内外研究进展,基于化学结构将这些抑菌天然产物分为醛类、黄酮类、烯类、醇类、多酚类、醌类、肽类和其他类化合物。通过阐述它们的抑菌机制,发现同类化合物的不同结构,特别是某些官能团的改变显著影响其抑菌性。另外,对细胞结构和细胞器的研究表明,细胞膜、线粒体多作为抑菌的靶标。抑制黄曲霉毒素合成的分子机制也成为目前研究抑菌天然产物的热点,主要集中在黄曲霉毒素合成通路中调节基因的表达变化上。在今后的研究中,抑菌天然产物仍需进一步开发,以期提高其稳定性及降低剂量。

Aspergillus flavus is a saprophytic filamentous pathogenic fungus,which presents widely in the storage and post-processing of grain. It has been ranked the second fungus causing aspergillosis after Aspergillus fumigatus. Meanwhile,the secondary metabolite,aflatoxin,has been classified as a primary carcinogen,which not only causes huge economic losses for China’s grain domestic demands and exports,but also seriously harms human and livestock health. Synthesized products are not as prevalent as before due to various disadvantages,such as harmful to human health and the environment,high residue,low degradation,and easy to induce resistance-strains,etc. Besides of physical and biological strategies in fighting against A. flavus,natural products have attracted great attentions for years. They constitute a large class of components or secondary metabolites derived from plants and microorganisms. Many of them are effective inhibitory compounds against A. flavus and have been classified as GRAS( Generally Recognized as Safe)and approved by FDA. Based on the research progress at home and abroad,this review screened the natural antifungal products reported previously and classified them into varied categories,including aldehydes,flavonoids,olefins,alcohols,polyphenols,quinones,peptides and other compounds according to their chemical structures. The main finds are as follows: in the same category,structures,especially the functional groups,affect their antifungal activities,which have been found in alcohols and quinones,revealing the structure-function relationship to some extent;moreover,extensive studies on cellular structures and organelles showed that cell membranes and mitochondria were usually destroyed strongly,indicating that the cell barrier and respiration metabolism were suppressed. In this case,components of cell membrane and mitochondria could be served as antifungal targets. Based on these findings,more natural antifungal products are still on the way to be developed,either by modifying the functional groups or designing new ones targeting specific organelles or components. However,the safety of natural products should also be carefully assessed by cellular and animal experiments prior to the application of food storage,processing,and preservation,etc. Besides of the inhibition of A. flavus growth,another hot topic in recent years is the molecular mechanism of inhibition against aflatoxins synthesis,which focuses on the expression changes of genes participating aflatoxins synthesis and regulation. However,fungi might switch to other pathways and the probable new secondary metabolites should be carefully determined. To sum up,promising antifungal products should possess the qualities of growth inhibition as well as aflatoxin-synthesis suppression. In the future,it is required to further develop potential natural antifungal products,and meanwhile,increase their stability and decrease the dosage.