Exploring Chemical and Biological Space of Terpenoids

Abstract

Terpenoids represent the largest family of natural products (NPs) with dramatically chemical and structural diversity, which makes terpenoids the important compound resources of drug discovery. However, comprehensive understanding on the structure− function features for terpenoid NPs is limited. In this work, we have systematically explored the chemical and biological space of terpenoid NPs, including their distribution, physicochemical properties, scaffold features, and functional applications, by utilizing various cheminformatics and bioinformatics approaches. We have not only confirmed that terpenoid NPs have good drug-likeness and great potential for drug discovery but, more importantly, illuminated the uniqueness of cyclic scaffold diversity in different species (plants, fungi, bacteria, and animals) and the specificity of biological function for the dominant fused-ring scaffolds of terpenoids. The present work supplies a valuable reference for identifying the new structure and unknown function of terpenoid NPs.

The biosynthesis of the anti‐microbial diterpenoid leubethanol in Leucophyllum frutescens proceeds via an all‐cis prenyl intermediate

“…Typically beginning with three common C10, C15, and C20 trans -prenyl diphosphate substrates, hundreds of mono-, sesqui-, and diterpene backbones are cyclized by terpene synthases (TPSs) ( Degenhardt et al ., 2009 ; Durairaj et al ., 2019 ; Johnson et al ., 2019a ). These backbones are further diversified to thousands of terpenoids ( Zeng et al ., 2019 ) through successive modification by enzymes such as cytochrome P450 mono-oxygenases, aldehyde dehydrogenases, and acetyl transferases ( Luo et al ., 2016 ; Pateraki et al ., 2017 ; Johnson et al ., 2019b ; Karunanithi and Zerbe, 2019 ). Diterpenoids (C20) make up more than 13 000 known plant terpenoids ( Johnson et al ., 2019a ), and the vast majority with known biosynthetic pathways are derived from all- trans ( E,E,E )-geranylgeranyl diphosphate (GGPP).…”

Analysis of the Acid/Base Profile of Natural Products from Different Sources

“…In light of this renaissance of natural products, the systematic analyses of the structural and chemical properties of these substances are of paramount importance in drug discovery, agriculture, and Foodinformatics . To date, there have been several chemoinformatic studies of natural products libraries, semisynthetic compound collections, and food chemicals . The focus of those studies was primarily on the chemical space of the compounds based on structure (in terms of fingerprints and scaffolds) and physicochemical properties of pharmaceutical relevance e. g., molecular weight, hydrogen bond donors, hydrogen bond acceptors, the octanol and/or water partition coefficient, topological polar surface area and, number of rotatable bonds …”

Chemotaxonomic investigation of plant terpenoids with an established database (TeroMOL)

“…Atomic frameworks (atomic scaffolds), are described in which linkers and ring systems of the molecule are kept at the atomic level (Bemis & Murcko, 1996). This protocol is realised by RDK it as was similarly done in our previous work (Zeng et al ., 2019).…”

“…Terpenoids comprise the largest part of natural products that are ubiquitous in plants, microorganisms, animals and other forms in Nature (Zeng et al ., 2019). As shown in Fig.…”