Microbial Biotransformation

What is Biotransformation

Biotransformation is also called bioconversion, this is the structural modifications in a chemical compound by organisms /enzyme, that lead to the formation of new molecules.

Biotransformation has great potential to generate novel products or to produce known products more efficiently.

The production of food metabolites, fine chemicals and pharmaceuticals can be achieved by biotransformation using biological catalysts, Cell suspension cultures and by using immobilized cells in a suitable carrier matrix.

Natural transformation process is slow, nonspecific and less productive. Microbial bio-transformations or microbial biotechnology are gaining importance and extensively utilized to generate metabolites in bulk amounts with more specificity.

"biotransformation refers to the chemical modification of a compound by biological systems, leading to a structurally altered product that is often more useful, active, or less toxic. Biotransformation is different from biosynthesis where complex products are assembled from simple substrates by whole cells, organs or organisms."

They are also different from biodegradations in which complex substances are broken down to simple ones.

Classification of Microbial Biotransformation

Based on the nature of the biological catalyst involved, biotransformation is broadly classified into two types.

(a) enzymatic biotransformation and

(b) non-enzymatic (microbial) biotransformation.

Enzymatic biotransformation

Enzymatic biotransformation involves the use of isolated enzymes as biocatalysts to convert a substrate into a specific product. These enzymes may be free in solution or immobilized on solid supports.

Non-enzymatic or microbial biotransformation

Non-enzymatic or microbial biotransformation uses whole living microorganisms such as bacteria, fungi, or yeast to carry out chemical transformations.

Initially the selected microbial strain is activated by placing them in suitable culture medium and when the microbial cells are become in activated phase then substrate is added for bioconversion into desired product. In bioconversion reactions, the substrate is taken up by the microbial cell and modified through a series of intracellular enzymatic reactions (bioconversion reactions) into desired product.

Large-scale transformation reactions were carried out in aerated and stirred bioreactors under sterile conditions.

This approach is extensively used in the biotransformation of steroids, alkaloids, antibiotics, and agrochemicals.

Microbial cells are ideal choice for biotransformation due to certain reasons like:

Types of Biotransformation reactions

Biotransformation reactions are of many types:

• Oxidation Reactions
• Hydrolytic Reactions
• Condensation Reactions
• Reduction Reactions

Oxidation Microbial Biotransformation Reaction

Oxidation biotransformation in microbial cells involves the introduction of oxygen or removal of hydrogen from the substrate by enzymes such as oxidases and dehydrogenases.

Hydrolytic Microbial Biotransformation Reaction

Hydrolytic biotransformation occurs when microbial enzymes like esterases, proteases, or amidases cleave chemical bonds in the presence of water.

Condensation Microbial Biotransformation Reaction

Condensation biotransformation involves the joining of two or more molecules by microbial enzymes with the elimination of a small molecule such as water. Such reactions are important in biosynthetic pathways, leading to the formation of larger and more complex bioactive compounds.

Reduction Microbial Biotransformation Reaction

Reduction biotransformation is mediated by microbial reductases that add hydrogen or remove oxygen from the substrate. These reactions often convert double bonds, carbonyl groups, or nitro groups into reduced forms, resulting in less reactive or more stable products.

Application of Microbial Biotransformation to Pharmaceuticals

Transformation of Steroids And Sterols

Steroids are natural compounds widely found in bile salts, adrenal cortex, sex hormones, alkaloids and in some antibiotics.

Transformation of Non-Steroidal Compounds

Dihydroxy acetone from glycerol

Dihydroxy acetone is used in lotions and various creams, cosmetics. Various acetic acid bacteria such as gluconobactor melanogenus perform this conversion.

Industrially, dihydroxyacetone is produced by biotransformation of glycerol using microorganisms—most commonly Acetobacter species (e.g., Acetobacter xylinum / Gluconobacter oxydans). In this process, glycerol is oxidized by the microbial enzyme glycerol dehydrogenase, converting it into dihydroxyacetone.

Prostaglandines

In this approach, fungi such as Rhizopus, Cunninghamella, and Aspergillus species are used to bioconvert suitable fatty acid or steroid-like precursors into prostaglandins.

Prostaglandines used as contraceptives, to reduce pain during child birth, for the treatment of congenital heart failure and in some digestive diseases.

Production of L-ascorbic acid (Vitamin-C)

D-sorbitol is biologically oxidized to L-sorbose by bacteria such as Acetobacter or Gluconobacter. This microbial oxidation is the most important bioconversion reaction in the pathway. The L-sorbose formed is then converted through further chemical steps into L-ascorbic acid.

Transformation of Antibiotics

Microbial transformation of existing antibiotics leads to development of newer, Modified and improved antibiotics, which contains many qualities like reduced toxicity, broad antimicrobial spectrum, enhanced oral absorption, less resistance and lesser allergic reactions.

Example:

• Streptomyces parvulus produced new actinomycines with better pharmacological activities.
• Lankacidin C, an antibiotic, which was esterified to lankacidin C 8-butyrate by the microbe Bacillus megaterium. lankacidin C 8-butyrate has improved antimicrobial activity and lesser side effects.
• Microbial transformation of antibiotics leads to improved drugs with reduced toxicity, enhanced absorption, and lesser resistance. For example, Streptomyces parvulus produces improved actinomycins.
• Dalapon (2,2-dichloropropionic acid), a chlorinated herbicide, is converted into pyruvate by certain soil microorganisms through enzymatic dehalogenation. This reaction is important because it demonstrates how microorganisms can detoxify xenobiotic compounds and convert them into central metabolic intermediates like pyruvate, which can then enter normal metabolic pathways such as the TCA cycle.

• DDT (dichloro-diphenyl-trichloroethane) undergoes reductive dechlorination under anaerobic conditions by microorganisms present in soil and sediments.
  This reaction is important because it represents a natural detoxification pathway in soil and sediment environments. DDD is less toxic and less insecticidal than DDT and helping to reduce their adverse environmental impact.