In silico Targeting, inhibition and analysis of polyketide synthase enzyme in Aspergillus ssp

Aflatoxins are toxic and carcinogenic components produced by some Aspergillus species such as Aspergillus flavus. Polyketide synthases enzyme (PKS) plays a central role in aflatoxin s biosynthesis of in Aspergillus flavus, 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 in silico 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, 14b-Hydroxy bufa-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. (C) 2020 Published by Elsevier B.V. on behalf of King Saud University.