Labib Mai M, Amin M K, Alzohairy A M, Elashtokhy M M A, Samir O, Saleh I, Arif I A, Osman G H, Hassanein S E
Agriculture Genetic Engineering Research Institute (AGERI), Egypt.
Faculty of Agriculture, Zagazig University, Department of Genetics.
Saudi J Biol Sci. 2020 Dec;27(12):3187-3198. doi: 10.1016/j.sjbs.2020.10.012. Epub 2020 Oct 27.
Aflatoxins are toxic and carcinogenic components produced by some species such as Polyketide synthases enzyme (PKS) plays a central role in aflatoxin s biosynthesis of in , especially the product template (PT) domain, which controls the aldol cyclization of the polyketide forerunner during the biosynthesis of the aflatoxin pathway process. Here, we apply the approaches to validate 623 natural components obtained from the South African Natural Compound Database (SANCDB), to distinguish the PT domain s prospected inhibitors. From the 623 compounds, docking results showed that there are 330 different compounds with energy binding lower than the natural substrate (palmitic acid or PLM) of the Product Templet domain (PT). Three factors were selected to determine the best 10 inhibiting components; 1) energy binding, 2) the strengthen chemical interactions, 3) the drug-likeness. The top ten inhibiting components are kraussianone 6, kraussianone 1, neodiospyrin, clionamine D, bromotopsentin, isodiospyrin, spongotine A, kraussianone 3, 14β-Hydroxybufa-3,5,20,22-tetraenolide and kraussianone 7. The chemical interactions between 3HRQ domain and the natural substrate in the active site amino acids are highly similar to the 3HRQ with the top ten components, but the main differences are in the binding energy which is the best in the top ten ligands. Those ten components give successful inhibition with PT domain which will lead to the formula to be used for inhibition and control aflatoxin contamination of agriculture crop yields and lessen the degree of harming and sicknesses that are coming about because of acquiring measures of aflatoxin.
黄曲霉毒素是由某些物种产生的有毒且致癌的成分，例如聚酮合酶（PKS）在黄曲霉毒素的生物合成中起着核心作用，尤其是产物模板（PT）结构域，它在黄曲霉毒素生物合成途径过程中控制聚酮前体的醛醇环化。在此，我们应用相关方法对从南非天然化合物数据库（SANCDB）中获取的623种天然成分进行验证，以鉴别PT结构域的潜在抑制剂。从这623种化合物中，对接结果显示有330种不同化合物的结合能低于产物模板结构域（PT）的天然底物（棕榈酸或PLM）。选择三个因素来确定最佳的10种抑制成分：1）结合能，2）增强的化学相互作用，3）类药性。排名前十的抑制成分是kraussianone 6、kraussianone 1、新柿皮素、clionamine D、溴托普辛、异柿皮素、海绵骨针素A、kraussianone 3、14β-羟基蟾毒-3,5,20,22-四烯醇内酯和kraussianone 7。活性位点氨基酸中3HRQ结构域与天然底物之间的化学相互作用与3HRQ和排名前十的成分高度相似，但主要区别在于结合能，结合能在前十种配体中是最佳的。这十种成分对PT结构域有成功的抑制作用域有成功抑制作用，这将产生用于抑制和控制农作物黄曲霉毒素污染的配方，并减轻因摄入黄曲霉毒素量而导致的危害程度和疾病。
