Introductory Chapter: Secondary Metabolites - An Overview

*Girish Nair, Suresh Selvapuram Sudalaimuthu Raja and Ramasamy Vijayakumar*

### **1. Introduction**

The metabolism can be defined as the collection of all the biochemical reactions held in an organism. Metabolites are the intermediate products of metabolism. Metabolites have various functions, including fuel, structure, and signaling, stimulatory and inhibitory effects on enzymes, catalytic activity of their own, defense, and interactions with other organisms. A primary metabolite is directly involved in normal growth, development, and reproduction of the host cell. A secondary metabolite is not directly involved in those processes, but usually has an important ecological function [1]. Secondary metabolites are biochemical compounds with varied and sophisticated chemical structures, produced by strains of certain microbial, animal and by plant species. Products of secondary metabolism are that the metabolites are usually not produced during the phase of rapid growth (trophophase), but are synthesized during a subsequent production stage (idiophase). Herbal plants, animals, and microorganisms such as bacteria, actinobacteria, cyanobacteria, fungi, and algae attracted more attention in research that led to the discovery of secondary metabolites. The exploration of secondary metabolites from various resources subsequently led to the development of drugs for the treatment of human diseases of microbial origin. Routine screening of natural resources will introduce novel secondary metabolic products with high pharmaceutical value [2].

Secondary metabolites, complex group of natural metabolic products, serve as defense chemicals, quorum sensing metabolites in environmental interactions, symbiosis, transport of metals and solutes. And in doing so, they confer selective advantage of survival over competitors, though their absence does not compromise their vegetative growth [3]. Twenty-five percent of about 1 million natural secondary metabolites are biologically active. Plants contribute 60% of these metabolites, and microorganisms form the rest, among which fungi remain major (42%) producers of bioactive compounds [4, 5].

#### **2. Taxonomy of secondary metabolites**

There are five main classes of secondary metabolites such as terpenoids and steroides, fatty-acid-derived substances and polyketides, alkaloids, nonribosomal polypeptides, and enzyme cofactors [6].

#### **2.1 Terpenoids and steroides**

Terpenes are the polymers of five carbon isoprene units and considered as the biggest class of secondary metabolites. When terpenes get modified by different functional groups and oxidized methyl groups at various positions, they form terpenoids. Depending on the carbon units, terpenoids can be divided into monoterpenes, sesquiterpenes, diterpenes, sesterpenes, and triterpenes. They find use in the anticancer treatment, as fragrance agent in cosmetics, and as food flavoring agent [7]. Steroids are diverse class of secondary metabolites and play an important physiological and biochemical function in the living organisms in which they are found. They are lipophilic, low molecular weight and are derived from cholesterol, the family of steroids includes sterols, bile acids, a number of hormones (both gonadal and adrenal cortex hormones), and some hydrocarbons. A number of synthetic steroids are being extensively used as anti-hormones, contraceptive drugs, anticancer agents, cardiovascular agents, osteoporosis drugs, antibiotics, anesthetics, anti-inflammatories, and anti-asthmatics. Many plant-derived sterols known as phytosterols are also used as dietary supplement as they are able to lower cholesterol in human body and prevent cancer [8].

#### **2.2 Fatty-acid-derived substances and polyketides**

A fatty acid is the carboxylic acid with aliphatic chain and is a form of energy reserve in the body called fats. Derivatives of fatty acid have a wide variety of industrial application such as plastics, lubricants, and fuels; they include hydroxy fatty acids, fatty alcohols, fatty acid methyl/ethyl esters, and fatty alkanes [9]. Polyketides (PKs) are produced by the action of polyketide synthases (PKSs) in animals, plants, fungi, and bacteria. These biologically active secondary metabolites display a high structural diversity and find many applications in treatment of various acute and chronic diseases. Examples include antibacterial (erythromycin and tetracycline), antitumor (anthracycline and doxorubicin), antifungal (amphotericin and griseofulvin), antiparasitic (avermectin), and anti-cholesterol (lovastatin) drugs. The acetyl tranferease, ketosynthase, thioesterase, and other such domains constitute polyketides. Linkage of acyl-coenzyme A (CoA) on the acyl carrier protein (ACP) facilitates biosynthesis of polyketides with catalytic support from AT domain [10].

#### **2.3 Alkaloids**

Plants are regarded as the oldest source of this natural occurring structurally diverse bioactive secondary metabolite. Some of the most widely recognized alkaloids, such as morphine, quinine, strychnine, and cocaine, are derived from plants. Alkaloids are small organic molecules containing nitrogen usually in a ring. In plants, they are mainly involved in defense against herbivores and pathogens. Rapid advances in molecular biology and metabolic engineering have led to discovery and synthesis of alkaloids also from microbes. Alkaloids can be classified according to their molecular weight, such as the indole alkaloids and isoquinoline alkaloids (each more than 4000 compounds). Other important groups include tropane alkaloids (∼300 compounds), steroidal alkaloids (∼450 compounds), and pyridine and pyrrolizidine alkaloids (respectively, ∼250 and 570 compounds) [11].
