Biotransformation

Biotransformations are changes in the structure of a chemical substance caused by organisms/enzyme systems, which result in the synthesis of molecules with higher polarity. This method came into existence in microbes to adapt to environmental changes and is beneficial in a variety of biotechnological activities. The most important feature of biotransformation is that it keeps the original carbon skeleton when the products are obtained.

Here, we will study the biotransformation of drugs, biotransformation metabolism, and microbial biotransformation in detail.

Biotransformation of Xenobiotics

A few enzymes with broad substrate specificities perform xenobiotic biotransformation.

Hydrolysis, reduction, and oxidation are all part of Phase I processes. These reactions normally result in just a minor increase in hydrophilicity by exposing or introducing a functional group (—OH, —\[NH_{2}\], —SH, or —COOH).

Glucuronidation, sulfonation (also known as sulfation), acetylation, methylation, and conjugation with glutathione (mercapturic acid production) are all Phase II biotransformation events that usually result in increased hydrophilicity and elimination.

The metabolic conversion of endogenous and xenobiotic substances to more water-soluble molecules is known as biotransformation. In general, a xenobiotic's physical properties are modified from those that encourage absorption (lipophilicity) to those that favor excretion in urine or feces (hydrophilicity). The removal of volatile chemicals through exhales is an exception to this general norm.

Biotransformation of Drugs

A xenobiotic's biological effects may be altered through chemical change via biotransformation. Biotransformation converts some medications into active metabolites that have pharmacodynamic or hazardous effects. Biotransformation, on the other hand, usually ends the pharmacologic effects of a drug and reduces the toxicity of xenobiotics. Enzymes that catalyze biotransformation events are important in determining the strength and duration of pharmacological activity, as well as chemical toxicity and carcinogenesis.

Types of Biotransformation

There are two types of biotransformation:

• Enzymatic 

• Non-Enzymatic 

Enzymatic Biotransformation

Enzymatic biotransformation is further divided into  Microsomal and Non-microsomal. The poison biochemistry that occurs owing to the presence of numerous enzymes in the body is known as elimination. Enzymes found in the lipophilic membranes of the smooth endoplasmic reticulum are responsible for microsomal biotransformation. 6 Non-Microsomal is a term used to describe a type of organism that is The enzymes found within the mitochondria play a role in biotransformation. Alcohol dehydrogenase, which converts ethanol to acetaldehyde, Tyrosine hydrolases, Xanthine oxidase, which converts hypoxanthine to xanthine, and other enzymes are examples.

Non-Enzymatic Biotransformations

Biotransformations that are spontaneous, non-catalyzed, and non-enzymatic are for highly active, unstable chemicals that occur at physiological pH. Clorazepate is converted to Desmethyldiazepam, Mustin HCl is converted to Ethylene Immonium, Atracurium is converted to Laudanosine, Quaternary acid is converted to Formaldehyde, and Hexamine is converted to Formaldehyde.

Microbial Biotransformation

Microbial biotransformation is widely employed in the transformation of a wide range of contaminants and chemicals, such as hydrocarbons, pharmaceuticals, and metals. Oxidation, reduction, hydrolysis, isomerization, condensation, formation of new carbon bonds, and introduction of functional groups are all examples of transformations.  Microbial biotransformation has long been recognized as a critical tool for reducing the production of various chemicals used in food, pharmaceutical, agrochemical, and other industries.

In the field of pharmaceutical research and development, biotransformation studies have been extensively employed to explore the metabolism of substances utilizing animal models. The microbial biotransformation phenomenon is thus often utilized in comparing metabolic pathways of medications and scaling up the metabolites of interest revealed in these animal models for further pharmacological and toxicological evaluation.

Biotransformation in Biotechnology

White biotechnology entails the use of microbial biotransformation to create desired compounds. Bacteria, filamentous fungi, mammals, plants, algae, yeast, and actinomycetes are among the 11 living cells used.

Microbial cells are an excellent candidate for biotransformation for a variety of reasons, including:

• The surface-volume ratio of microbial biotransformation is very high.

• Growth Rate: Microbial cells with a faster growth rate convert biomass faster.

• Metabolism Rate: A faster metabolism rate in microorganisms leads to more effective substrate transformation.

• When bacteria are used, it is easier to maintain sterile conditions.

Applications of Microbial Biotransformation

1. Biotransformation of Steroids

Steroids are a type of natural substance found in bile salts, adrenal-cortical and sex hormones, insect molting hormones, sapogenins, alkaloids, and some antibiotics.  The first microbial biotransformation of steroids took place in 1937. Corynebacterium sp. was used to make testosterone from dehydroepiandrosterone. Using Nocardia spp. Cholesterol was synthesized from 4-dehydroeticholanic and 7-hydroxycholesterol.

The basic structure of all steroids is cyclopentanoperhydrophenanthrene, which is made up of four fused rings. Cortisone is effective against rheumatoid arthritis and skin problems due to its anti-inflammatory properties. By altering the structure of cortisone, specifically by inserting a 1,2 double bond in ring A, prednisone is produced, which has a considerably improved anti-inflammatory action.

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2. Biotransformation of Antibiotics

The goal of microbial transformation of existing antibiotics is to generate novel, modified, and better antibiotics with properties such as lower toxicity, a broad antibacterial range, improved oral adsorption, and less resistant/allergic effects.  In most situations, any transformation phase results in antibiotic deactivation, either partially or completely. Here are a few typical instances of the numerous possible reactions:-

Indirect Transformation: Affected antibiotics are generated in the presence of inhibitors or changed precursors in the media during regulated biosynthesis. Streptomyces parvulus, for example, creates two novel actinomycins that contain cis-4-methyl proline instead of proline. When mutations that prevent the manufacturing of a certain antibiotic were utilized, they discovered 24 new compounds. Only a few better antibiotics, such as 5-epi-sisomicin, have been developed using mutational synthesis and are currently being tested in clinical studies.

Direct Transformation: The antibiotics were inactivated by hydrolysis of the functional groups.

3. Biotransformation of Toxicants

Plant disease and pest control agents are essential for the world's population's existence. High compound stability is necessary for vector control systems, yet this stability has a negative impact on the environment.

Microbial transformation is of interest in this regard, not for the generation of new active agents, but for the maximum feasible environmental detoxification. This entails xenobiotic enzymatic transformations. Xenobiotics can be removed from the ecosystem using a variety of methods.

Cometabolism: Cometabolism usually results in a simple alteration of molecules, which might result in toxicity reduction or increase. The microorganisms involved do not acquire energy from the transformation reaction and must thrive on a different substrate. The combined action of various organisms can result in the complete disintegration of a chemical. Dehalogenation events, for example, are key cometabolism processes that may allow pesticide molecules to be broken down further.

Biotransformation and Metabolism

Both the terms biotransformation and metabolism are often used synonymously when applied to drugs. The term metabolism is often used to describe the fate of a xenobiotic, which consists of absorption, distribution, biotransformation, and elimination. However,  metabolism is used to mean biotransformation, which is understandable from the point that the products of xenobiotic biotransformation are known as metabolites. Furthermore, individuals with a genetic enzyme deficiency resulting in impaired xenobiotic biotransformation are described as poor metabolizers rather than poor bio transformers.

Benefits of Biotransformation

1. The simplicity with which the biological method can be used in a typical organic chemistry laboratory.

2. Enzymes, baker's yeast, and a variety of microorganisms are commercially available.

3. The ease with which one can dive right into complex chiral products to evaluate their biological, industrial, and medical applications.

4. Biocatalysts (enzymes) are generally more efficient catalysts than chemical catalysts. In comparison to chemical catalysts, biocatalysts require a very low concentration (10-3 to 10-4 mol percent of catalysts) for an enzymatic process (0.01 -1 mol percent ).

5. The availability of method recommendations for selecting the best microbe for the desired conversion.

6. Microbial transformations occur under benign conditions, such as at room temperature and near-neutral pH, avoiding the issues of isomerization, racemization, epimerization, and rearrangement that beset the classic chemical technique.

7. Enzyme systems are very efficient and selective in terms of the reactions catalyzed as well as the substrate's structure and stereochemistry. Decomposition, isomerization, racemization, and rearrangement, all of which can be problematic in chemical reactions, are reduced when enzymes are used.

8. In contrast to the simple stereospecific enzymatic conversions, stereospecific chemical conversions or even a simple organic compound require a complicated organometallic reagent that is expensive, difficult to produce in a small laboratory, and not suitable for industrial use. Enzymes can tell the difference between the two enantiomers of a racemic substrate. As a result, just one enantiomer is targeted, resulting in only one selective product.

9. Biotransformations have reaction specificity, regiospecificity, and stereospecificity, as well as the ability to be performed under mild reaction circumstances. Even though numerous groups of comparable molecules assault the substrate molecule, it is usually targeted at a single place.

Did You Know?

There are some disadvantages of biotransformation:

1. The costs of developing a biotransformation process, which includes product isolation, are usually rather substantial.

2. Most of the time, the reaction time is quite long.

3. The concentrations of substrate and product are minimal, and the biocatalysts' stability is limited.

4. The bulk of biotransformation reactions involving separated enzymes are being adopted from the post-1970 era, thanks to developments in fermentation technology and the introduction of cheaper enzymes. The spectrum of processes currently known to be catalyzed by isolated enzymes is extensive, seemingly limited only by the ease with which these biocatalysts may be isolated, their stability, and their cost.

5. Genetic engineering and recombinant DNA approaches in this sector have the potential to make pricey enzymes more affordable and to partially or completely overcome many of the current limits on the use of isolated enzymes in biotransformation.

6. Biotransformations can be carried out using a variety of biocatalysts. This is most likely why the subject of biotransformation has seen such tremendous expansion since 1970. Furthermore, there is a lot of interest in this field all across the world.