Scaffold and Structural Diversity of the Secondary Metabolite Space of Medicinal Fungi.

Abstract

Medicinal fungi, including mushrooms, have well-documented therapeutic uses. 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 medicinal fungi has similar or higher scaffold diversity in comparison to other natural product libraries analyzed here. Notably, 94% of the scaffolds in the secondary metabolite space of medicinal fungi are not present in the approved drugs. Further, we find that the secondary metabolites, on the one hand, are structurally far from the approved drugs, while, on the other hand, they are close in terms of molecular properties to the 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.