Biodegradation of Xenobiotics compounds

E-module

By

Dr.Jitender Kumar

Department of Biotechnology

HMV,Jalandhar

Introduction

• These are man made chemicals present inn environment in very high concentrations.
• Xenobiotic (xenos-foregin) broadly refer to the unnatural, foreign and synthetic chemicals such as pesticides, herbicides, refrigerants, solvents and other organic compounds.
• Not produced naturally.
• Produced at much lower concentration than that by man.

Types of Xenobiotics compounds

• Hydrocarbons
• Polychlorinated biphenyls(PCB,S)
• Synthetic polymers
• Alkylbenzyl sulphonates
• Oil mixtures
• Other xenobiotics compound

Biodegradation vs biotransformation

• Biodegradation or biological degradation is the phenomenon of biological transformation of organic compounds by living organisms, particularly the microorganisms.
• Biodegradation basically involves the conversion of complex organic molecules to simpler (and mostly non-toxic) ones.
• The term biotransformation is used for incomplete biodegradation of organic compounds involving one or a few reactions.

Biodegradation vs biotransformation

• Biotransformation is employed for the synthesis of commercially important products by microorganisms.
• Bioremediation refers to the process of using microorganisms to remove the environmental pollutants i.e. the toxic wastes found in soil, water, air etc.
• The microbes serve as scavengers in bioremediation.
• The removal of organic wastes by microbes for environmental clean-up is the essence of bioremediation.
• The other names for bioremediation are bio-treatment, bio-reclamation and bio-restoration.
• It is rather difficult to show any distinction between biodegradation and bioremediation.

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Metabolism of xenobiotics

• In some cases, phase 1 metabolic reactions convert xenobiotics from inactive to biologically active compounds.
• In these instances, the original xenobiotics are referred to as prodrugs or procarcinogens.
• Sometimes, additional phase 1 reactions (eg, further hydroxylation reactions) convert these active compounds into less active or inactive forms prior to conjugation.
• In yet other cases, it is the conjugation reactions themselves that convert the active products of phase 1 reactions to less active or inactive compounds, which are excreted.
• In a very few cases, conjugation may increase the biological activity of a xenobiotic.

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Metabolism of xenobiotics

• Microbial degradation of xenobiotic assumes significance, since it provides an effective and economic means of disposing of toxic chemicals, particularly the environmental pollutants.
• Pseudomonas — The predominant microorganism for Bioremediation: Members of the genus Pseudomonas (a soil microorganism) are the most predominant microorganisms that degrade xenobiotic.
• Different strains of Pseudomonas, that are capable of detoxifying more than 100 organic compounds, have been identified.
• The examples of organic compounds are several hydrocarbons, phenols, organophosphates, polychlorinated biphenyls (PCBs) and polycylic aromatics and naphthalene.
• About 40-50 microbial strains of microorganisms, capable of degrading xenobiotics have been isolated.
• Besides Pseudomonas, other good examples are Bacillus,Mycobacterium, Alcaligenes, and Nocardia.

BIOMEDICAL IMPORTANCE�

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• Xenobiotics are a wide variety of foreign chemicals , both naturally occurring compounds in plant foods, and synthetic compounds in medicines, food additives, and environmental pollutants.
• Knowledge of the metabolism of xenobiotics is essential for an understanding of pharmacology and therapeutics, toxicology, and the management of disease.
• All these areas involve either the administration of, or exposure to, xenobiotics.
• Many of the xenobiotics in plant foods have potentially beneficial effects and knowledge of their metabolism will permit extrapolation from in vitro measurement of antioxidant activity to in vivo protective action.
• Understanding the mechanisms involved in xenobiotic metabolism will permit the development of transgenic microorganisms and plants containing genes that encode enzymes for the metabolism of specific compounds that can be used to convert potentially hazardous pollutants to harmless compounds.
• Similarly, transgenic organisms may be used for biosynthesis of drugs and other chemicals.

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Metabolism of xenobiotics

• A xenobiotic (Gk xenos “stranger”) is a compound that is foreign to the body.
• The principal classes of xenobiotics of medical relevance are drugs, chemical carcinogens, naturally occurring compounds in plant foods, and various compounds that have found their way into our environment by one route or another, such as polychlorinated biphenyls (PCBs), insecticides and other pesticides.
• While the metabolism of xenobiotics is generally considered to be a process of detoxification, sometimes the metabolites of compounds that are themselves inert or harmless are biologically active.

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Metabolism of xenobiotics

• The metabolism of xenobiotics is generally considered in two phases.
• In phase 1, the major reaction involved is hydroxylation, catalyzed mainly by members of a class of enzymes referred to as onooxygenases or cytochromes.
• In addition to hydroxylation, these enzymes catalyze a wide range of reactions, including those involving deamination, dehalogenation, desulfuration, epoxidation, peroxygenation, and reduction.
• Reactions involving hydrolysis (eg, catalyzed by esterases) and certain other nonP450-catalyzed reactions also occur in phase 1.
• Phase 1 metabolism renders compounds more reactive, introducing groups that can be conjugated with glucuronic acid, sulfate, acetate, glutathione, or amino acids in phase 2 metabolism.
• This produces polar compounds that are water soluble and can therefore readily be excreted.

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Degradation

• Xenobiotic compounds have been degraded by physical and chemical methods.
• Coagulation, filtration, adsorption, chemical precipitation, electrolysis, and ozonation.
• Microbial degradation
• Toxicity
• Carcinogenicity
• Bioaccumulation

Co-metabolism

• Co-metabolism in biodegradation: In general, the metabolism (breakdown) of xenobiotics is not associated with any advantage to the microorganism.
• That is the pollutant chemical cannot serve as a source of carbon or energy for the organism.

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Co-metabolism

• The term co-metabolism is often used to indicate the non-beneficial to the microorganismand biochemical pathways concerned with the biodegradation of xenobiotics.
• Use of substrate as growth promotors.
• However, co- metabolism depends on the presence of a suitable substrate for the microorganism.
• Such compounds are referred to co-substrates.

Factors Affecting Biodegradation:

• Several factors influence biodegradation.
• These include the chemical nature of the xenobiotic, the capability of the individual microorganism, nutrient and Oxygen supply, temperature, pH and redox potential.
• Among these, the chemical nature of the substrate that has to be degraded is very important.

Factors Affecting Biodegradation:

• Some of the relevant features are given here under:
• In general, aliphatic compounds are more easily degraded than aromatic ones.
• Presence of cyclic ring structures and length chains or branches decrease the efficiency of biodegradation.
• Water soluble compounds are more easily degraded.
• Molecular orientation of aromatic compounds influences biodegradation i.e. ortho > para > meta.
• The presence of halogens (in aromatic compounds) inhibits biodegradation.

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Bio-stimulation:

• This is a process by which the microbial activity can be enhanced by increased supply of nutrients or by addition of certain stimulating agents (electron acceptors, surfactants).
• These factors also stimulate degradation of xenobiotic compound.

Enzyme for Biodegradation

• Several enzyme systems (with independent enzymes that work together) are in existence in the microorganisms for the degradation of xenobiotics.
• The genes coding for the enzymes of bio-degradative pathways may be present in the chromosomal DNA or more frequently on the plasmids.
• In certain microorganisms, the genes of both chromosome and plasmid contribute for the enzymes of biodegradation.
• The microorganism Pseudomonas occupies a special place in biodegradation.

References

• General Microbiology by R.P.Singh
• Biotechnology expanding horizon by B.D.Singh
• Stanbury, P.F., Whitaker, A. and Hall, S.J. (2001), Principles of Fermentation Technology 2nd ed., Pergamon Press, Oxford.

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• Thank You