CLASSIFICATION OF SECONDARY METABOLITES.pptx

It is about classification of secondary metabolites in botany

1. CLASSIFICATION OF SECONDARY METABOLITES LIN MARY PAUL I PG BOTANY AM24BOT007

2. CONTENT SECONDARY METABOLITES CLASSIFICATION TERPENOIDS BIOSYNTHESIS OF TERPENOIDS PHENOLICS N CONTAINING COMPOUNDS S CONTAINING COMPOUNDS

3. WHAT ARE SECONDARY METABOLITES? Secondary metabolites are small molecules or organic compounds that are produced by plants. However, they aren’t directly involved in their development, normal growth, and reproduction. Instead, they mediate certain functions that increase their survival and fecundity (reproductive ability). Based on the structure of the compounds, the secondary metabolites are classified into: Terpenoids Phenolics Alkaloids etc.

4. CLASSIFICATION

5. T ERPENOIDS Terpenoids—with over 30,000 members described to date—take the honors for being the largest class of small molecule natural products in plants. They exhibit enormous structural diversity, but are united by a common biosynthetic origin. Derived from the joining of five‐carbon isopentane units, te r penoids are also referred to as isoprenoids and as terpenes. The terms “terpene” and “terpenoid” originate from the word turpentine (“terpentin” in German) because some of the first terpenes described were isolated from turpentine. The five-carbon units from which terpenoids are formed are sometimes called isoprene units, because some terpenoids decompose to give off the gas isoprene at elevated temperatures .

6. They are polymeric isoprene derivatives and synthesized from acetate via the mevalonic acid pathway. During their formation, the isoprene units are linked in head and tail fashion , meaning the "head" of one isoprene unit connects to the "tail" of the next isoprene unit; the "head" is considered the end of the molecule near the branch point, while the "tail" is the opposite end of the carbon chain. The number of units incorporated into a particular terpene serves as a basis for their classification. Many of them have pharmacological activity and are used for diseases treatment both in humans and animals. Note : The mevalonic acid pathway, also known as the isoprenoid pathway, is a metabolic pathway that produces isoprenoids and other essential molecules. It's found in eukaryotes, archaea, and some bacteria. The classification of terpenoids has a long history , The 10‐carbon terpenoids were once thought to be the smallest naturally occurring repr e sentatives of this class. Hence, these were called monoterpenes, and the name persists. The terpenoids are classified based on the number of isoprene units in the molecule. It includes: Hemiterpene : It consists of a single isoprene unit. Its examples include isovaleric acid from Vaccinium myrtillus, and angelic acid isolated from Angelica archangelica.

7. Monoterpene : It consists of two isoprene units. They are further classified based on their structure as hydrocarbons, alcohol, ketones, alcohol , esters, and aldehydes. Its examples are Carvone, Linalool, Limonene, Linalyl acetate, and Citronellal. Sesquiterpene : It has three isoprene units. Its examples include caryophyllene and farnesol. A number of these compounds show antibacterial, antiprotozoal, and antifungal activities. Diterpene : It contains four isoprene units. A few examples of this group are gibberellins, cembrane, phytane, and labdane. They possess a range of medicinal activities, including antifungal, antibacterial, analgesic, anti-inflammatory, and antineoplastic activities. Sesterterpenes : It consists of five isoprene units. Its example is geranyl farnesol. Triterpenes : It has six isoprene units. An example of triterpene is quassin. Sesquarterterpene : It is composed of seven isoprene units. Tetraterpene : It contains eight isoprene units. Its examples are carotenoids and xanthophylls. Polyterpene : It includes molecules having more than eight isoprene units. An example of this group of terpene is natural rubber.

8. Biosynthesis of Terpenoids Although many types of terpenoids exist, they have similar synthetic pathways. The terpenoid biosynthesis pathway is divided into three steps. 1 . C5 Precursor IPP and DMAPP Formation Phase The C5 precursor consists of two isomers, IPP and DMAPP , which are mainly synthesized from MVA and MEP. The MVA pathway includes six steps of enzymatic reactions, providing precursors for sesquiterpenes, phytosterols, and triterpenoids such as brassinolide and ubiquinones in the mitochondria. The MEP pathway consists of seven enzymatic steps that mainly act as substrate sources for monoterpenes, diterpenes, carotenoids, and their decomposition products (cytokinins, gibberellins, chlorophyll, tocopherols, and plastids). [I sopentenyl pyrophosphate (IPP) and D imethylallyl pyrophosphate (DMAPP) ].

9. 2 . Direct Precursor Formation Stage Geranyl pyrophosphate (GPP, C10), farnesyl pyrophosphate (FPP, C15), and geranylgeranyl pyrophosphate (GGPP, C20) are the main direct precursors of most terpenoids. GPP is synthesized by the action of GPP synthase (GPS) , which is a precursor in monoterpene synthesis. GPS exists in two forms: a homodimer composed of two identical subunits, and a heterodimer composed of a small and a large subunit. FPP is a precursor for the synthesis of sesquiterpenes, triterpenes, and sterols, which are formed by the condensation of one DMAPP molecule and two IPP molecules. GGPP is a precursor of many important substances in plants, including chlorophyll, carotenoids, gibberellins, and tocopherols. It is produced from three IPP molecules and one DMAPP molecule under the action of bovine pyrophosphate synthase (GGPS). Interestingly, GGPS can also act as a large subunit of the GPS heterodimer.

10. 3. Terpene Formation and Modification Stage There have been many studies on the formation stages of IPP, DMAPP, and their direct precursors, and all terpenoids must undergo these two stages. There are few studies on the third stage, especially on the modification processes of terpenoids, yet this stage is the main factor in the enrichment of terpenoid diversity. Most terpenes are catalyzed by terpene synthase (TPS), which removes the bisphosphate groups of the direct precursors GPP, FPP, and GGPP to form monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20), and polyterpene skeletons. Squalene synthase (SQS/farnesyl diphosphate farnesyltransferase) and phytene synthetase (PSY/geranylgeranyl diphosphate gerany ltransferase) can also directly condense two FPP or GGPP molecules to form the sterol precursor squalene (C30) and the carotenoid precursor octahydrolycopene (C40). After terpenoid carbon skeleton synthesis, terpenoids can be further modified by redox reactions, methylation, acylation, and glycosylation by cytochrome P450 (CYP) and other modifying enzymes, thus providing terpenoids with various structures, complex chemical properties, and unique functional characteristics.

11. T he main function of CYP is to oxidize terpenes. For example, in plants, (E,E)-geranyllinalool and (E)-nerolidol can produce the terpene homologues TMTT and DMNT, respectively, under the action of P450 enzymes encoded by AtCYP82G1, and these two substances produce important anti-insect effects in many plants. 4. Transport of Terpenoids Few studies have been conducted on the transport and emission of terpenoids in plants after their synthesis. In recent years, following in-depth studies of terpenoid metabolic pathways, an increasing number of researchers have begun to study terpenoid transport. They have found that terpenoid transport is related to ABC transporters. For example, in the leaves of Vinca minor, VmABCG1, a member of the superfamily of ABC transporters, is involved in the emission of the nonvolatile monoterpene indole alkaloid vinblastine.

12. In addition, in the hairs of Artemisia annua, sesquiterpene (E)-caryophyllene transport is completed under the action of AaPDR3, a member of the ABC transporter superfamily .Capsidiol emissions from Nicotiana benthamiana are related to NbABCG1 and NbABCG2. However, the substrate specificity of these transporters and the reversibility of their transport directions are unclear and require further study.

13. OVER VIEW All terpenoids are formed from repeating units of 5-carbon building blocks called isoprenes . To date, the best known biosynthetic pathway of terpenoids include mevalonic acid as an intermediate and hence called the mevalonate pathway . The starting primary metabolite for terpenoids synthesis is acetyl-CoA that goes through a series of reactions to condense three molecules of acetyl-CoA to mevalonic acid . The six-carbon mevalonic acid is the immediate precursor of the basic 5-carbon building blocks, isopentenyl diphosphate (IPP) and dimethylallyl pyrophosphate (DMAPP ; also called dimethylallyl diphosphate). The condensation of DMAPP and IPP in head to tail fashion provides a 10-carbon skeleton of geranyl diphosphate (GPP ). The GPP is the immediate precursor of all monoterpenes. A further 5-carbon unit addition to GPP leads to farnesyl pyrophosphate (FPP) as the immediate precursor of sesquiterpenes (15 carbon), while one more unit addition gives geranylgeranyldiphosphate ( GGPP ) as a precursor of diterpenes (20 carbon). On the other hand, the dimers of FPP yield triterpenes (30 carbon), while GGPP can dimerize to give tetraterpenes (40 carbon).

14. PHENOLICS Phenolic compounds are diverse in size and complexity but generally share a basic structure: an aromatic (phenyl) ring with at least one hydroxyl group attached. This hydroxyl group is acidic, allowing phenolic compounds to be reactive and suited for forming large polymers like lignins or suberins, which contribute to the plant's structural integrity. They also play significant roles in various physiological processes and defense mechanisms. Phenolic compounds are classified in several ways, based on functional groups or the number of phenol units. Some of the major subclasses include flavonoids, anthocyanidins, isoflavones, chalcones, stilbenes, coumarins, furanocoumarins, lignans, and others like naptha- and anthraquinones.

15. The approach to classifying plant phenolics are based on: (1) A number of hydroxylic groups. So, they may be divided on 1-, 2- and polyatomic phenols. OH Phenol OH OH Phenolic compounds containing more than one OH-group in aromatic ring are polyphenols; (2) C hemical composition: mono-, di, oligo- and polyphenols; (3) S ub stitutes in carbon skeleton, a number of aromatic rings and carbon atoms in the side chain. According to the latter principle, phenolic compounds are divided into four main groups: phenolics with one aromatic ring, with two aromatic rings, quinones and polymers. Phenolic compounds with one aromatic ring: a large number of compounds, among them are simple phenols (C6), phenol with attached one (C6-C1), two (C6-C2) and three (C6-C3) carbon atoms. Phenolic compounds with two aromatic rings: this group includes benzoquinones and xanthones (C6-C1-C6) containing two aromatic rings which are linked by one carbon atom; stylbenes (C6-C2-C6) which are linked by two carbon atoms; and flavonoids, containing three carbon atoms (C6-C3-C6). Flavonoids, depending on the structure of propane unit and an attaching place of side chain B, are divided into flavonoids in strict sense, which are derived from chromane or chromone, isoflavonoids and neoflavonoids. Polyphenolics are more than 8,000 different compounds identified to date. Based on these differences, polyphenols can be subdivided into two classes: flavoinoids and non flavonoids, like tannins .

16. Simple Phenolics : They are defined as compounds having at least one hydroxyl group attached to the basic skeleton of an aromatic ring. It includes compounds like gallic acid, eugenol, catechol, salicylic acid, hydroquinone, and thymol. Coumarins : It’s a derivative of benzo-α-pyrone. Clover and melotot are the richest sources of coumarins. Its examples are esculetin, scopoletin, and umbelliferone. Tannin : These are water-soluble phenol derivatives. They are of two types: hydrolyzable tannins and condensed tannins. Its examples include gallotannins, geraniin, and ellagitannins. Flavonoids : These are the largest group of phenolics secondary metabolites, found in almost all vegetables and fruits. Its examples are quercetin, cyanidin, delphinidin, and luteolin. It’s predominantly found in the Umbelliferae, Polygonaceae, Leguminosae, Compositae, and Rutaceae families of plants. Lignans : They are dimeric compounds, formed by joining two molecules of phenylpropene derivative. Their examples include matairesinol and Wikstrom. Stilbenes : They are a widely distributed small group of phenolic compounds. Its example is resveratrol. Chromones and Xanthones : These are structural derivatives of benzo-γ-pyrone. They are not of much pharmaceutical importance. Their examples are eugenin, khellin, and furanochromones.

17. N-CONTAING COMPOUNDS The A lkaloids present the group of secondary metabolites that contain basic nitrogen atoms. Some related compounds with neutral and weakly acid properties are also included in the alkaloids. In addition to carbone, hydrogen and nitrogen, this group may also contain oxygen, sulfur and rarely other element such as chlorine, bromine and phosphorus. Alkaloids are produced by a large variety of organisms, such as bacteria, fungi, animals but mostly by plants as secondary metabolites. Most of them are toxic to other organisms and can be extracted by acid-base. They have diverse pharmacological effects , and have a long history in medication. The boundary between alkaloids and other nitrogen-containing natural compounds is not clear-cut. Compounds like amino acids, proteins, peptides, nucleotides, nucleic acid, and amines are not usually called alkaloids.