TOPIC III

DRUGS FROM SYNTHESIS

 DRUGS FROM BIOSYNTHESIS
Biosynthesis is a process of forming larger organic compounds from small subunits within a
living organism.
Biosynthesis is mainly done by enzymes.
Biosynthesis is also known as anabolism since simple compounds are joined together to form
macromolecules by enzymes.
As an example, photosynthesis occurs inside the chloroplast.
The light energy is converted into chemical energy during photosynthesis.
The larger molecule glucose is biosynthesized from water and carbon dioxide by
photosynthetic organisms.(ATP, Enzyme, Cofactors)
 Biosynthesis of Primary Metabolites
Living plants are solar-powered biochemical and biosynthetic laboratory which manufactures both primary and
secondary metabolites from air, water, minerals and sunlight.

The primary metabolites like sugars, amino acids & fatty acids that are needed for general growth & physiological
development of plant which distributed in nature & also utilized as food by man.

The secondary metabolites such as alkaloids, glycosides, Flavonoids, volatile oils etc are biosynthetically derived
from primary metabolites.

Biosynthetic reactions are replica of common organic reactions like catalytic reactions, phosphorylation, hydride
transfer, oxidation, elimination, acylation, alkylation, reduction, condensation, rearrangement etc
 Metabolism & Metabolic Pathways
 Cell Metabolism: Process by which living cell process nutrient molecule & living
state.
 Metabolic Pathway: A complete set of chemical reactions that occur in living cells,
allowing cells to grow and reproduce, maintain their structures, and respond to their
environments.
 Living cell require energy for biosynthesis, transport of nutrient, motility and
maintenance.
 Energy is obtained from the catabolism of carbon compounds (carbohydrate)
 Carbohydrates are synthesized from CO2 and H2O in the present of light by
photosynthesis.
 Calvin Cycle
The Calvin cycle is the last step in photosynthesis.
The purpose of the Calvin Cycle is to take the energy from photosystem I and fix carbon.
Carbon fixation means building organic molecules by adding carbon onto a chain.
The following formula summarizes the Calvin cycle.
C5 + CO2 + ATP + NADPH → C6H12O6
Where C5 is a five carbon molecule, such as pyruvate, when is recycled as glucose is synthesized.
The first step in the Calvin cycle is for the 3C5 to bind with 3CO2, producing a six 3-carbon organic molecules
(6C3).
Next, 6ATP and 6NADPH energizes the binding of a C3 to make a 6- carbon molecule (C6), glucose.
The remaining 5C3 continues moving through the Calvin cycle, being turned back into the starter C5 organic
molecule
 Mevalonate pathway
The mevalonate pathway begins with acetyle-CoA and ends with the production of
Isopentenyl pyrophosphate (IPP)and Dimethylally pyrophosphate (DMAPP) which
are used to make isoprenoids, a diverse class of over 30,000 biomolecules such as
cholerestrol , Vitamin K, and all steroid hormones.

One of the important pathway for the synthesis of different types of secondary
metabolites cells of plant
 Acetate-Malonate pathway
The main products of the acetate-malonate pathway are the fatty acids, both those primary
metabolites which occur universally and the more unusual compounds with a restricted
distribution.

Acetate-Malonate pathway includes synthesis of fatty acids and aromatic compounds with the
help of secondary metabolites.

Main precursors of Acetate-Malonate Pathway are Acetyl-CoA and Malonyl-CoA.

End product of this pathway can be saturated or unsaturated fatty acids or polyketides
 SHIKIMIC ACID PATHWAY
•The Shikimic acid pathway is a key intermediate from carbohydrate for the biosynthesis of
C6-C3units (phenyl propane derivative).
•The Shikimic acid pathway converts simple carbohydrate precursors derived from glycolysis
and the pentose phosphate pathway to the aromatic amino acids.
•The shikimate pathway is a 7 step metabolic route used by bacteria, fungi, Algae, parasites,
and plants for the biosynthesis of aromatic amino acids (phenylalanine, tyrosine, and
tryptophan).
•This pathway is not found in animals; therefore, phenylalanine and tryptophan represent
essential amino acids that must be obtained from the animal's diet.
•Animals can synthesize tyrosine from phenylalanine, and therefore is not an essential amino
acid except for individuals unable to hydroxylate phenylalanine to tyrosine).
Shikimic acid pathway
The shikimate pathway (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 (tryptophan, phenylalanine, and tyrosine). This pathway is not found in animal cells.

Shikimic acid is a primary progenitor of the pharmaceutical manufacturing as antiinfluenza drug

oseltamivir

The seven enzymes involved in the shikimate pathway are DAHP synthase, 3-dehydroquinate synthase,
3-dehydroquinate dehydratase, shikimate dehydrogenase, shikimate kinase, EPSP synthase, and
chorismate synthase.
 Bacterial transformation
Plasmid or vector transformation is the process by which exogenous DNA is transferred into the host cell.
Transformation usually implies uptake of DNA into bacterial, yeast or plant cells, while transfection is a term
usually reserved for mammalian cells.
Bacterial cells acquire DNA from their environment through a process known as transformation.
The way that bacterial cells absorb DNA from their environment is through transformation.
As was already established, bacterial transformation refers to the reception of DNA molecules from the outside
environment through the cell wall followed by their stable inclusion into the recipient genome or replication as
an independent plasmid.
A viable donor cell is not necessary for gene transfer by transformation; all that is needed is for persistent
DNA to exist in the surrounding environment.
 Bacterial transformation
Bacterial transformation is a method of horizontal gene transfer whereby some bacteria take in unprocessed
DNA from their environment.
Researchers first insert a DNA fragment, such as a gene, onto a plasmid, a circular piece of DNA, in a
conventional cloning procedure.
This procedure, known as ligation, makes use of DNA ligase and restriction enzymes.
The next step after ligation is transformation, which involves transferring the DNA into bacteria.
 Bacterial transformation
In the late 1900s, scientists engineered bacteria to include the gene for the human insulin protein. After
being grown in large vats, the bacteria pumped out insulin, which was then purified and given to
humans.

Employing bacteria to fight cancer dates back to the late 19th century when an oncologist, William B.
Coley, deliberately infected his cancer patients with Streptococcus pyrogenes, the agent that causes
strep throat. as the bacteria accumulated in the tumors of Coley’s patients, they triggered an immune
response and competed with the tumor cells for nutrients, essentially starving the tumor cells to death.
infection with bacteria engineered to produce a cancer drug should be even more effective.