Virtual Screening of Compounds Produced by Streptomyces Bacteria Against Type I 3- Dehydroquinase

Abstract

The rise of mul -drug resistant bacterial strains has presented a challenge in the !eld of drug discovery and healthcare, with the discon nua on of now-ineBec ve treatments and the need to develop novel strategies in controlling diseases caused by pathogenic bacteria exempli!ed by Escherichia coli and Salmonella enterica. This report focused on delving into the possibility of compounds produced by the bacterial genus Streptomyces in inhibi ng the shikimate pathway enzyme type I 3-dehydroquinase. The work involved a virtual screening and docking campaign against a collec on of Streptomyces-produced compounds for their ability to inhibit type I 3-dehydroquinase. Although a bioac vity screening campaign, taking into considera on reported mechanisms of ac on of the screened compounds, revealed fumaramidmycin and xanthocidin as plausible candidates against the target enzyme, none were shown to be able to inhibit said enzyme owing to binding a?ni es and therefore inhibi on constants lower than that of the natural ligand, 3-dehydroquinate. Nevertheless, it was revealed that nega ve binding a?ni es were obtained from the docking of xanthocidin with a model of type I 3-dehydroquinase from Clostridioides di cile, opening a possibility for modi!ca ons on the ligands to improve binding a?nity towards said enzyme.