Scaffold and structural diversity of the secondary metabolite space of medicinal fungi

Abstract

Medicinal fungi including mushrooms have well documented therapeutic uses. The MeFSAT database provides a curated library of more than 1800 secondary metabolites produced by medicinal fungi for potential use in high throughput screening (HTS) studies. In this study, we perform a cheminformatics based investigation of the scaffold and structural diversity of the secondary metabolite space of medicinal fungi, and moreover, perform a detailed comparison with approved drugs, other natural product libraries and semi-synthetic libraries. We find that the secondary metabolite space of MeFSAT has similar or higher scaffold diversity in comparison to other natural product libraries analysed here. Notably, 94% of the scaffolds in the secondary metabolite space of MeFSAT are not present in the approved drugs. Further, we find that the secondary metabolites of medicinal fungi, on the one hand are structurally far from the approved drugs, while on the other hand are close in terms of molecular properties to approved drugs. Lastly, chemical space visualization using dimensionality reduction methods showed that the secondary metabolite space has minimal overlap with the approved drug space. In a nutshell, our results underscore that the secondary metabolite space of medicinal fungi is a valuable resource for identifying potential lead molecules for natural product based drug discovery.