Biosynthetic Pathways of Secondary Metabolites PDF

Biosynthetic pathways of Secondary metabolites Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined together to form macromolecul...

Biosynthetic pathways of Secondary metabolites Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined together to form macromolecules. This process often consists of metabolic pathways. The building blocks are tiny chemical molecules produced from primary metabolites mostly from photosynthesis, glycolysis, and or Krebs cycle. They are very important in biosynthesis and production of secondary metabolites. These are considered to be intermediates, few important ones are acetyl CoA, shikimic acid , mevalonic acid malonic acid. The building blocks can be segregated based on the number of Carbon units C1 derived from S methyl of L-methionine C2 derived from acetyl –CoA C5 derived from isoprene units C6-C3 units (phenyl propyl units) are derived from phenylalanine or tyrosine through shikimic acid pathway. The Basic Metabolic Pathways Leading To Production of Secondary MetabolitesThrough Photosynthesis Biosynthesis pathway of natural products: 1. Shikimic-acid (shikimate) pathway The shikimic acid pathway (shikimate pathway) is the basic process for biosynthesis of phenolic compounds, alkaloid, and others. It takes place in chloroplast plant cells and have the phenylpropanoid precursors. These aromatic compounds are types of secondary metabolites that abundant in plant, and the expression of them are triggered by environmental stresses, such as pathogens and herbivores attack, inappropriate pH and temperature, UV radiation, saline stress, and heavy metal stress. Shikimic acid pathway is a seven-step metabolic pathway used by bacteria, archaea, fungi, algae, some protozoans, and plants for the biosynthesis of folates and aromatic amino acids (phenylalanine, tyrosine, and tryptophan).The pathway starts with two substrates, phosphoenol pyruvate and erythrose-4-phosphate, and ends with chorismate, a substrate for the three aromatic amino acids. Figure 1: overview of shikimate pathway with the enzymatic process  Figure2.The synthesize process of three aromatic amino acids as protein building blocks produces through shikimate(chorismate) biosynthetic pathway Shikimate biosynthetic pathway is also known as the chorismate pathway. Figure 1 shows the overview of shikimate pathway with the enzymatic process, Phosphoenolpyruvate and erythrose-4-phosphate react to form 3-deoxy-D- arabino- heptulosonate 7-phosphate, in a reaction catalyzed by the enzyme DAHP synthase. The next enzyme involved is shikimate kinase, an enzyme that catalyzes the ATP dependent phosphorylation of shikimate to form shikimate 3-phosphate. Shikimate-3-phosphate is then coupled with phosphoenol pyruvate to give 5- enolpyruvylshikimate-3-phosphate via the enzyme 5-enolpyruvylshikimate-3- phosphate (EPSP) synthase. Then 5-enolpyruvylshikimate-3-phosphate is transformed into chorismate by a chorismate synthase. and the next phase is aromatic amino acid synthesis that produced by shikimate pathway in Figure 2: Tryptophan (L-Trp), Tyrosine (L-Tyr), and Phenylalanine (L- Phe), as molecular building blocks for protein , alkaloids , phenols and other biosynthesis. The shikimate pathway is being a metabolic pathway that connecting central and specialized metabolism in the plant cell and carbon degradation during the synthesis of secondary metabolite compounds. 2. Malonic-acid (Malonate/Acetate) pathway Acetate pathway operates functionally with the involvement of acyl carrier protein (ACP) to yield fatty acylthioesters of ACP. These acyl thioesters forms the important intermediates in fatty acid synthesis. These C2 acetyl CoA units at the later stage produces even number of fatty acids from n-tetranoic (butyric) to n-ecosanoic (arachidic acid). In fatty acid synthesis, acetyl‐CoA is the direct precursor only of the methyl end of the growing fatty acid chain. All the other carbons come from the acetyl group of acetyl‐ CoA but only after it is modified to provide the actual substrate for fatty acid synthase. Malonyl‐CoA contains a 3‐carbondicarboxylic acid, malonate, bound to Coenzyme A. Malonate is formed from acetyl‐CoA by the addition of CO2 using the biotin cofactor of the enzyme acetyl‐CoA carboxylase. Figure 3. The acetate –malonate pathway for biosynthesis of fatty acids 3. Mevalonic-acid (Mevalonate) pathway The mevalonic acid (MVA) pathway or mevalonate pathway also known as the isoprenoid pathway that involves the synthesis of 3-hydroxy-3- methylglutaryl-CoA reductase (HMGCR). Moreover, the MVA pathway is the core of metabolic pathway for multiple cellular metabolisms in eukaryotic, archaea, and some bacteria organisms, including cholesterol biosynthesis and protein. Cholesterol is produced as the molecules that used to build the membrane cell structure, steroid hormones, myelin sheets in neuron system, precursors of vitamin D, formation and release of synaptic vesicles. Mevalonic acid further produced isopentenyl pyrophosphate (IPP) and its isomer dimethylallyl pyrophosphate (DMAPP). These two main intermediates IPP and DMAPP set the ‘active isoprene’ unit as a basic building block of isoprenoid compounds. Both of these units yield geranyl pyrophosphate (C10-monoterpenes) which further association with IPP produces farnesyl pyrophosphate (C15-sesquiterpenes). Farnesyl pyrophosphate with one more unit of IPP develops into geranyl-geranyl pyrophosphate (C20-diterpenes). The farnesyl pyrophosphate multiplies with its own unit to produce squalene, and its subsequent cyclization gives rise to cholesterols and other groups like triterpenoids. Figure4.Mevalonate(MVA)pathway.