In silico efficacy of [S]-8-gingerol (a derivative) with 6-gingerol against PT-domain of Polyketide synthase A (PksA)

Abstract

The PT-domain of Polyketide synthase A (PksA) is crucial product template that controls the aldol cyclization and aromatization to create polyketide precursor. The precursor leads to biosynthesis of aflatoxin secondary metabolites. Being carcinogenic in nature of these secondary metabolic, efforts have been made to explore novel inhibitors targeting the PT-domain of PksA. Previously, [6]-gingerol reported as a prospective inhibitor for the inhibition for aflatoxin biosynthesis, but some of its derivatives such as (S)- [8]-gingerol, 9-Hydroxy-[6]-gingerol, 9-gingerol, 5-O-methyl-[9]-gingerol, methyl-6-gingerol, and [5]-gingerol exhibited better binding affinity. Notably, Leu1508, Asn1554, and Asn1568, are the key amino acid residues that are involved in stabilizing ligand-protein interaction. The study explores the understanding to develop new approach to create novel drug against the PT-domain to restrict the aflatoxin biosynthesis at initiation. However, a detailed in vivo study is required to further evaluation at in vivo stage.