Tiwari Shraddha, Shishodia Sonia K, Shankar Jata
Genomic laboratory, Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Solan, Himachal Pradesh 173234 India.
3 Biotech. 2019 Apr;9(4):149. doi: 10.1007/s13205-019-1675-y. Epub 2019 Mar 25.
Studies on phytochemicals as anti-aflatoxigenic agents have gained importance including quercetin. Thus, to understand the molecular mechanism behind inhibition of aflatoxin biosynthesis by quercetin, interaction study with polyketide synthase A (PksA) of was undertaken. The 3D structure of seven domains of PksA was modeled using SWISS-MODEL server and docking studies were performed by Autodock tools-1.5.6. Docking energies of both the ligands (quercetin and hexanoic acid) were compared with each of the domains of PksA enzyme. Binding energy for quercetin was lesser that ranged from - 7.1 to - 5.25 kcal/mol in comparison to hexanoic acid (- 4.74 to - 3.54 kcal/mol). LigPlot analysis showed the formation of 12 H bonds in case of quercetin and 8 H bonds in hexanoic acid. During an interaction with acyltransferase domain, both ligands showed H bond formation at Arg63 position. Also, in product template domain, quercetin creates four H bonds in comparison to one in hexanoic acid. Our quantitative RT-PCR analysis of genes from aflatoxin biosynthesis showed downregulation of and at 24 h time point in comparison to 7 h in quercetin-treated . Overall results revealed that quercetin exhibited the highest level of binding potential (more number of H bonds) with PksA domain in comparison to hexanoic acid; thus, quercetin possibly inhibits via competitively binding to the domains of polyketide synthase, a key enzyme of aflatoxin biosynthetic pathway. Further, we propose that key enzymes from aflatoxin biosynthetic pathway in aflatoxin-producing could be explored further using other phytochemicals as inhibitors.
对包括槲皮素在内的植物化学物质作为抗黄曲霉毒素生成剂的研究变得越发重要。因此，为了了解槲皮素抑制黄曲霉毒素生物合成背后的分子机制，开展了与聚酮合酶A（PksA）的相互作用研究。使用SWISS-MODEL服务器对PksA七个结构域的三维结构进行建模，并通过Autodock tools-1.5.6进行对接研究。将两种配体（槲皮素和己酸）的对接能量与PksA酶的各个结构域进行比较。槲皮素的结合能较低，范围为-7.1至-5.25千卡/摩尔，而己酸为-4.74至-3.54千卡/摩尔。LigPlot分析表明，槲皮素形成了12个氢键，己酸形成了8个氢键。在与酰基转移酶结构域相互作用时，两种配体在Arg63位置均形成氢键。此外，在产物模板结构域中，槲皮素形成了四个氢键，而己酸形成了一个氢键。我们对黄曲霉毒素生物合成基因的定量RT-PCR分析表明，与槲皮素处理7小时相比，在24小时时间点， 和 基因表达下调。总体结果显示，与己酸相比，槲皮素与PksA结构域的结合潜力最高（氢键数量更多）；因此，槲皮素可能通过竞争性结合聚酮合酶的结构域来抑制黄曲霉毒素生物合成途径的关键酶。此外，我们建议可以使用其他植物化学物质作为抑制剂，进一步探索产黄曲霉毒素的 中黄曲霉毒素生物合成途径的关键酶。
