Biotechnology assignment

Biotransformation
Biotransformation is the chemical modification (or modifications) made by an organism on a chemical
compound. Biotransformation means chemical alteration of chemicals such as nutrients, amino acids,
toxins, and drugs in the body.

Biotransformation is a process by which organic compounds are transformed from one form to another
to reduce the persistence and toxicity of the chemical compounds. This process is aided by major range
of microorganisms and their products such as bacteria, fungi and enzymes. Biotransformation can also
be used to synthesize compounds or materials, if synthetic approaches are challenging. Natural
transformation process is slow, nonspecific and less productive. Microbial biotransformation or
microbial biotechnology are gaining importance and extensively utilized to generate metabolites in bulk
amounts with more specificity. This review was conceived to assess the impact of microbial
biotransformation of steroids, antibiotics, various pollutants and xenobiotic compounds.

Types of biotransformation
 Enzymatic
 Non-enzymatic. 

Enzymatic Biotransformation:
 Enzymatic Elimination is the biotransformation occurring due to various enzymes present in the body.
Enzymatic are further divided into Microsomal and Non-microsomal.

1. Microsomal biotransformation is caused by enzymes present within the lipophilic membranes of

smooth endoplasmic reticulum.

2. Non-Microsomal Biotransformation involves the enzymes which are present within the
mitochondria. Examples include: Alcohol dehydrogenase responsible for metabolism of ethanol into
acetaldehyde and Tyrosine hydrolases enzymes, Xanthine oxidase converting hypoxanthine into
xanthine etc.
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Non-enzymatic Biotransformation:
Spontaneous, non-catalyzed and non-enzymatic types of biotransformation are for highly active,
unstable compounds taking place at physiological pH. Some of these include Chlorazepate converted
into Desmethyl diazepam, Mustin HCl converted into Ethyleneimonium, Atracurium converted into
Laudanosine and Quartenary acid, Hexamine converted into Formaldehyde.

https://medcraveonline.com/JBMOA/microbial-bio-transformation-a-process-for-chemical-
alterations.html

Purpose and importance of biotransformation

The major purpose of biotransformation is to chemically modify (metabolize) poorly excretable lipophilic
compounds to more hydrophilic chemicals that are readily excreted in urine and/or bile. Without
metabolism, lipophilic xenobiotics accumulate in biota, increasing the potential for toxicity.

1. In the field of pharmaceutical research and development, biotransformation studies have been
extensively applied to investigate the metabolism of compounds (leads, lead candidates, etc.)
using animal models.
2. The microbial biotransformation phenomenon is then commonly employed in comparing
metabolic pathways of drugs and scaling up the metabolites of interest discovered in these
animal models for further pharmacological and toxicological evaluation.
3. Microorganisms can conveniently afford drugs difficult obtained via synthesis. The plethora of
reported microbial biotransformations along with its added benefits has already invoked further
research in bioconversion of novel and structurally complex drugs.

Pervaiz I, Ahmad S, Madni MA, et al. Microbial biotransformation: a tool for drug designing (Review).  Prikl
Biokhim Mikrobiol. 2013;49(5):435–449.

Biotransformation of Drug
Biotransformation of drug is defined as the chemical conversion of one form to another .the term is
synonymously used as METABOLISM, which is the major mechanism for drug elimination.

Sites for Drug Metabolism are;

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 Liver is the major site of drug metabolism

 But specific drugs may undergo transformation in other tissues like Kidneys and small intestne

Results of biotransformation of drug is

 Production of metabolites that are more polar then the parent drug
 Usually terminates the pharmacologic reaction of parent drug
 After phase 1 reaction similar or different pharmacologic activity or toxic activity
https://www.slideshare.net/DrZaigham/biotransformation-metabolism-of-drugs

Metabolism of Drug
The metabolism of a drug or toxin in a body is an example of a biotransformation. The body typically
deals with a foreign compound by making it more water-soluble, to increase the rate of its excretion
through the urine. There are many different processes that can occur; the pathways of drug metabolism
can be divided into:

 phase І
 phase II

Drugs can undergo one of four potential biotransformations: Active Drug to Inactive Metabolite, Active
Drug to Active Metabolite, Inactive Drug to Active Metabolite, and Active Drug to Toxic Metabolite
(biotoxification).

Phase І reaction

 Includes oxidative (via cytochrome P450), reductive, and hydrolytic reactions

OXIDATION:
Oxygen molecules are added in this reaction and Removal of hydrogen takes place. Group of
monooxygenases in liver are responsible for carrying out the reactions.
REDUCTION:
This reaction is the Reverse of oxidation in this Product drugs are chloralhydrate, chloramphenicol, and
halothane or nitro reduction occur by cytochrome P450.
HYDROLYSIS:
Cleavage of drug molecule is taking place by water molecule. This reaction takes place in liver, intestine,
plasma, and other tissues. For Examples choline, procaine, and oxytocin.
CYCLIZATION:
The Formation of ring structure from linear chain structure is called cyclization.
For Example, proguanil.
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DE-CYCLIZATION
The reaction taking to open a ring structure to make linear chain compound is known as de-cyclization.
Examples are phenytoin, barbiturates.
https://www.slideshare.net/MANISHmohan19/bio-transformation

 In these types of reactions, a polar group is either introduced or unmasked, so the drug

molecule becomes more water-soluble and can be excreted.
 Reactions are non-synthetic in nature and in general produce a more water-soluble and less active
metabolites.
 The majority of metabolites are generated by a common hydroxylating enzyme system known
as Cytochrome P450.

Phase II reaction
 These reactions involve covalent attachment of small hydrophilic endogenous molecule such
as glucuronic acid, sulfate, or glycine to form water-soluble compounds, that are more
hydrophilic.
 This is also known as a conjugation reaction.

GLUCURONIDE CONJUGATION:
Excretion of products in the bile is often required an enzyme called UDP-glucuronosyltransferase (UGT).
Conjugation of a- glucuronic acid to d- glucuronic acid. Enterohepatic recycling can occur due to gut
glucuronidase. Examples are diazepam, lorazepam, metronidazole etc.

ACETYLATION:
It is a common reaction for aromatic amines and sulfonamides. It requires co-factor acetyl-CoA. N-
acetyltransferase acts as a responsible enzyme.

METHYLATION:
It involves in the transfer of methyl group from S-adenosyl methionine (SAM) to the acceptor substrate
by various methyl transferase enzymes is known as methylation. E.g., adrenaline, histamine.
The final compounds have a larger molecular weight

https://www.omicsonline.org/biotransformation-open-access.php
https://en.wikipedia.org/wiki/Biotransformation

Diagram for phase I and phase ii reaction

Biotechnology assignment

https://upload.medbullets.com/topic/107006/images/350px-xenobiotic_metabolism.jpg

REFERENCES

https://medcraveonline.com/JBMOA/microbial-bio-transformation-a-process-for-chemical-
alterations.html
Pervaiz I, Ahmad S, Madni MA, et al. Microbial biotransformation: a tool for drug designing (Review).  Prikl
Biokhim Mikrobiol. 2013;49(5):435–449.
https://www.slideshare.net/DrZaigham/biotransformation-metabolism-of-drugs
https://en.wikipedia.org/wiki/Biotransformatio
https://www.slideshare.net/MANISHmohan19/bio-transformation
https://upload.medbullets.com/topic/107006/images/350px-xenobiotic_metabolism.jpg
https://www.omicsonline.org/biotransformation-open-access.php