Advanced Concepts and Applications

Fidele Ntie-Kang, Fidele Ntie-Kang

• Verlag: De Gruyter
• Jahr: 2021
• ISBN:
  9783110669060
• Auflage: 1
• Thema: Scienze fisiche
• Thema: Chimica analitica

Vol. 2 of Chemoinformatics of Natural Products introduces the reader to the currently available tools for toxicity prediction, drug property prediction, an enumeration of compounds, scaffolds and functional groups in nature, computational methods for lead identification, metabolite biosynthesis, etc. Selected case studies and hands-on tutorial exercises have been included.

Part I: Advanced Chemoinformatics Concepts for Natural Product-based Drug Discovery

1 An enumeration of natural products from microbial, marine and terrestrial sources

Fidele Ntie-Kang

Department of Chemistry, University of Buea, Buea, Cameroon

Department of Pharmaceutical Chemistry, Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany

Department of Informatics and Chemistry, University of Chemistry and Technology Prague, Praha, Czech Republic

Daniel Svozil

Department of Informatics and Chemistry, University of Chemistry and Technology Prague, Praha, Czech Republic

This article has previously been published in the journal Physical Sciences Reviews. Please cite as: Ntie-Kang, F., Svozil, D. An enumeration of natural products from microbial, marine and terrestrial sources. Physical Sciences Reviews [Online] 2019 DOI: 10.1515/psr-2018-0121

Abstract

The discovery of a new drug is a multidisciplinary and very costly task. One of the major steps is the identification of a lead compound, i.e. a compound with a certain degree of potency and that can be chemically modified to improve its activity, metabolic properties, and pharmacokinetics profiles. Terrestrial sources (plants and fungi), microbes and marine organisms are abundant resources for the discovery of new structurally diverse and biologically active compounds. In this chapter, an attempt has been made to quantify the numbers of known published chemical structures (available in chemical databases) from natural sources. Emphasis has been laid on the number of unique compounds, the most abundant compound classes and the distribution of compounds in terrestrial and marine habitats. It was observed, from the recent investigations, that ~500,000 known natural products (NPs) exist in the literature. About 70 % of all NPs come from plants, terpenoids being the most represented compound class (except in bacteria, where amino acids, peptides, and polyketides are the most abundant compound classes). About 2,000 NPs have been co-crystallized in PDB structures.

Keywords: drug discovery, functional groups, natural products, numbers, scaffolds,

1.1 Introduction

In the quest to discover new drugs, researchers have often resorted to natural sources, e. g. plants, marine organisms, bacteria and fungi [1, 2]. This is because these organisms are known to host sophisticated metabolic pathways that have led to complex and intriguing chemical structures. The existence of such structures could never have been figured out by any chemist, had nature not synthesized them. Besides, some naturally occurring compounds have required several decades to be synthesized, even after the entire chemical structure had been elucidated [3,4,5]. Such compounds are often the products of secondary metabolism in higher organisms, fungi, and microbes. Thus, they are often referred to as secondary metabolites (or natural products).

An attempt has been made to provide a classification of secondary metabolites (SMs) according to their structural diversity, bioactivity and ecological functions [6]. By so doing, an examination of the main natural product (NP) classes was carried out according to their metabolic building blocks, e. g. alkaloids, fatty acids, polyketides, phenylpropanoids, and aromatic polyketides, and terpenoids. This included a discussion of the structural diversity of natural product classes using the scaffold approach while focusing on the characteristic carbon frameworks.

Several key questions still, however, remain to be answered:

• How many naturally occurring compounds are currently known?
• How diverse are they?
• What are the most frequently occurring chemical scaffolds and functional groups (FGs) among secondary metabolites?
• Which of the main pool of NPs (marine, terrestrial or microbial) is the most promising source of new and biologically active compounds?
• What proportion of the biosphere is still unexplored in terms of organisms and in terms of their metabolite contents?

In summary, what future lies ahead of us in terms of the coverage of the chemical space of secondary m...