What is Biosynthesis?

The plant kingdom serves as a solar-powered biochemical laboratory which synthesizes both primary and secondary metabolites in presence of environmental factors such as air, water, minerals and sunlight. Metabolites are organic compounds synthesizes by organisms using enzyme mediated chemical reactions called metabolic pathways .


Acetate pathway

It is one of the most important pathway for the process of secondary metabolites.

Acetate occupies central position in relation to general metabolism.


Acetate pathway


1.Straight chain compound


2.Aromatic compound

Acetate pathway:

It consist of two main pathway

1. Acetate Mevalonate Pathway/ Isoprenoid Pathway

2. Acetate Melonate Pathway/ Fatty acid & Polyketides


1.The acetate pathway, is also known as Mevalonate pathway or HMG-CoA reductase pathway, is an essential metabolic pathway present in Eukaryotes, archaea, and some bacteria.


• The pathway produces two five – carbon building blocks called Isopentenyl Pyrophosphate (IPP) and Dimethyl allyl-Pyrophosphate (DMAPP).


The Mavalonate pathway begins with Acetyl CoA and ends with the production of IPP and DMAPP.

It is best known as the target of statins, a class of cholesterol lowering agent.


Occurance:


It occur in Eukaryotes,  archaea and bacteria and some higher plant and animals.
This is the structure of isoprene unit (C5H8)


isoprene

(2-methyl-1,3-butadiene)

Terpenes: The Isoprene Rule. Isoprenoids- C10 (terpenes), C15 (sesquiterpenes) and C20 (diterpenes) plant; essential oils

Ruzicka isoprene rule:  terpenoids are derived from “isoprene  units” (C5).





C25 sesterpenoids are derived from geranylfarnesyl diphosphate, which consists of five C5 “isoprene units” that are joined “head-to-tail”



C30 triterpenoids and steroids are derived from squalene, which consists of two C15 farnesyl units” that are joined “tail-to-tail”




C40 tetraterpenoids are derived from phytocene, which consists of two C20 geranylgeranyl units” that are joined “tail-to-tail”







Isopentyl Diphosphate: The Biological Isoprene Unit.


Mevalonic acid is the biosynthetic precursor to the actual C5 “isoprene units,” which are isopentyl diphosphate (IPP, tail) and dimethylallyl diphosphate (DMAPP, head).


Acetyl Mevalonate pathway starts with Acetyl CoA (which is the active form of Acetate) comes from the Glycolysis pathway, and finally it converts to Pyruvate.


Step 1: Two molecules of Acetyl CoA combines with each other and converts into the Aceto acetyl CoA by the enzyme Acetl CoA Thiolase.



Step 2: The acetoacetyl CoA combines with another Acetyl CoA to form 3-Hydroxy-3-methyl glutaryl CoA (HMD CoA) with the help of enzyme, HMG CoA Synthase.


Step 3: HMG CoA undergoes reduction to form Mevalonate with the help of enzyme,HMG CoA  Reductase and NADPH and 2H+.



 

Conversion of mevalonic acid to IPP and DMAPP


Step 4: Mevalonate undergoes phosphorylation in presence of ATP to form 5-Phospho-Mevalonate at position C-5, enzyme involved is Mevalonic acid 5-Phosphase.


Step 5: 5-phosphomevalante again undergoes Phosphorylation to form 5-Pyrophospho Mevalonate with the help of ATP.


Step 6: 5-Pyrophospho mevalonate is then converted to two important precursors i.e. Isopentenyl Pyrophosphate (IPP) and Dimethylallyl Pyrophosphate (DMAPP) which is responsible for the synthesis of different types of Isoprenoids with the help of enzyme 5-Pyroposphate decarboxylase.


Step 7: This Isopentenyl Pyrophosphate undergoes Isomerisation to form Dimehtyl allyl Pyrophosphate with the help of enzyme IPP Isomerase.


Carbon-Carbon Bond Formation in Terpene Biosynthesis.

Conversion of IPP and DMAPP to geraniol-PP and farnesyl-PP


Step 8: Isopentyl Pyrophosphate and Dimehtyl allyl Pyrophosphate undergoes condensation to form Geramyl Pyrophosphate.


Step 9: Geranyl Pyrophosphate is further converted to Formesyl Pyrophosphate due to the addition of IPP, with the release of P206.


Step 10: To the Formesyl Pyrophosphate, IPP is added to form Geranyl Geranyl Pyrophosphate.








Types of Mevalonate Pathway


1.Upper Mevalonate Pathway/Acetate Mevalonate Pathway

The Mevalonate pathway of Eukaryotes archaea and bacteria all begin the same way.
The sole carbon feed stock of the pathway is Acetyl CoA. The first step condenses two Acetyl CoA
molecules to yield Acetoacetyl CoA. This followed by a second condensation to form HMG-CoA 
(3-Hydroxy-3-Methyl-glutaryl-CoA).

Reduction of HMG-CoA  yields Mevalonate. These first three Enzymatic steps are called the 
upper Mevalonic pathway.

2. Lower Mevalonic Pathway/ Acetate Mevalonic pathway

 The lower mevalonate pathway which converts Mevalonate into IPP and DMAPP has 3 variants.
 In Eukaryotes, Mevalonate is phosphorylated twice in the 5-OH position, then decarboxylated to
yeild IPP.
In some archaea such as Haloferax volcanii, Mevalonate is phosphorylated once in the 5-OH
 position, decarboxylated to yeild Isopentenyl Phosphate (IP), and finally phosphorylated again to
yeild IPP. 

A third Mevalonate pathway variant found in Thermoplasma acidophilum, phosphorylates 
Mevalonate at the 3-OH position followed by phosphorylation at the 5-OH position.

The resulting metabolite, Mevalonate-3, 5-bisphosphate, is decarboxylated to IP and finally phosphorylated to yield IPP.

 

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