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Docking analysis of hexanoic acid and quercetin with seven domains of polyketide synthase A provided insight into quercetin-mediated aflatoxin biosynthesis inhibition in Aspergillus flavus

Tiwari, Shraddha, Shishodia, Sonia K., Shankar, Jata
3 Biotech 2019 v.9 no.4 pp. 149
Aspergillus flavus, aflatoxins, biochemical pathways, biosynthesis, energy, gene expression regulation, genes, hexanoic acid, ligands, polyketide synthases, quercetin, reverse transcriptase polymerase chain reaction, transferases
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 Aspergillus flavus 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 pksA, aflD, aflR, aflP and aflS at 24 h time point in comparison to 7 h in quercetin-treated A. flavus. 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 Aspergilli could be explored further using other phytochemicals as inhibitors.