The landscape of natural product diversity and their pharmacological relevance from a focus on the Dictionary of Natural Products®

Nature is considered a prolific source of diverse biologically active chemotypes. Medicinal plants have historically attracted the most attention and have led to the discovery of various drugs ranging from anticancer to anti-infectious agents. However, a vast array of bioactive metabolites have also been discovered from marine organisms, fungi and bacteria. While most reviews have focused on the characteristics of the chemical backbones of natural products (NPs), few have tried to provide an overview of their origins (the living organisms in which they are produced), chemical classes, and biological activities. This review discusses the current knowledge on NP diversity by focusing on the Dictionary of Natural Products® (DNP). We datamined the 300,000 NPs covered by the DNP to reveal relevant, albeit dormant, knowledge about NP diversity. This holistic picture of NPs allows us to discuss the most abundant biological sources of NPs investigated in relation to their chemical features and biological activities. In a nutshell, a large part of NPs originated from plants (67%), especially from the Compositae and Leguminosae families. Among all kingdoms, NPs isolated from Streptomyces spp. were largely represented, while terpenoids and alkaloids were the two most represented chemical classes. Out of all NPs documented, only 3,882 were reported to be bioactive (1,163 from plants and 1,006 from bacteria), with antibacterial, antibiotics, and antineoplastic agents being the most frequent therapeutic classes. In this paper, we also address the advantages and limitations of NP research from a pharmaceutical industry perspective. This work will provide useful insights and guidance to researchers involved in drug discovery from NPs.