Biotransformation

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Biotransformation is the chemical modification (or modifications) made by an organism on a chemical compound. If this modification ends in mineral compounds like CO2, NH4+, or H2O, the biotransformation is called mineralisation.

Biotransformation means chemical alteration of chemicals such as nutrients, amino acids, toxins, and drugs in the body. It is also needed to render nonpolar compounds polar so that they are not reabsorbed in renal tubules and are excreted. Biotransformation of xenobiotics can dominate toxicokinetics and the metabolites may reach higher concentrations in organisms than their parent compounds.[1]

Drug metabolism

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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, Active Drug to Toxic Metabolite (biotoxification).

Phase І reaction

  • Includes oxidative, reductive, and hydrolytic reactions.
  • In these type 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 polar endogenous molecule such as glucuronic acid, sulfate, or glycine to form water-soluble compounds.
  • This is also known as a conjugation reaction.
  • The final compounds have a larger molecular weight.

Microbial biotransformation

Biotransformation of various pollutants is a sustainable way to clean up contaminated environments.[2] These bioremediation and biotransformation methods harness the naturally occurring, microbial catabolic diversity to degrade, transform or accumulate a huge range of compounds including hydrocarbons (e.g. oil), polychlorinated biphenyls (PCBs), polyaromatic hydrocarbons (PAHs), pharmaceutical substances, radionuclides and metals. Major methodological breakthroughs in recent years have enabled detailed genomic, metagenomic, proteomic, bioinformatic and other high-throughput analyses of environmentally relevant microorganisms providing unprecedented insights into biotransformation and biodegradative pathways and the ability of organisms to adapt to changing environmental conditions.

Biological processes play a major role in the removal of contaminants and pollutants from the environment. Some microorganisms possess an astonishing catabolic versatility to degrade or transform such compounds. New methodological breakthroughs in sequencing, genomics, proteomics, bioinformatics and imaging are producing vast amounts of information. In the field of Environmental Microbiology, genome-based global studies open a new era providing unprecedented in silico views of metabolic and regulatory networks, as well as clues to the evolution of biochemical pathways relevant to biotransformation and to the molecular adaptation strategies to changing environmental conditions. Functional genomic and metagenomic approaches are increasing our understanding of the relative importance of different pathways and regulatory networks to carbon flux in particular environments and for particular compounds and they are accelerating the development of bioremediation technologies and biotransformation processes.[2] Also there is other approach of biotransformation called enzymatic biotransformation.

Oil biodegradation

Petroleum oil is toxic for most life forms and episodic and chronic pollution of the environment by oil causes major ecological perturbations. Marine environments are especially vulnerable, since oil spills of coastal regions and the open sea are poorly containable and mitigation is difficult. In addition to pollution through human activities, millions of tons of petroleum enter the marine environment every year from natural seepages. Despite its toxicity, a considerable fraction of petroleum oil entering marine systems is eliminated by the hydrocarbon-degrading activities of microbial communities, in particular by a remarkable recently discovered group of specialists, the so-called hydrocarbonoclastic bacteria (HCB). Alcanivorax borkumensis, a paradigm of HCB and probably the most important global oil degrader, was the first to be subjected to a functional genomic analysis. This analysis has yielded important new insights into its capacity for (i) n-alkane degradation including metabolism, biosurfactant production and biofilm formation, (ii) scavenging of nutrients and cofactors in the oligotrophic marine environment, as well as (iii) coping with various habitat-specific stresses. The understanding thereby gained constitutes a significant advance in efforts towards the design of new knowledge-based strategies for the mitigation of ecological damage caused by oil pollution of marine habitats. HCB also have potential biotechnological applications in the areas of bioplastics and biocatalysis.[3]

Metabolic engineering and biocatalytic applications

The study of the fate of persistent organic chemicals in the environment has revealed a large reservoir of enzymatic reactions with a large potential in preparative organic synthesis, which has already been exploited for a number of oxygenases on pilot and even on industrial scale. Novel catalysts can be obtained from metagenomic libraries and DNA sequence based approaches. Our increasing capabilities in adapting the catalysts to specific reactions and process requirements by rational and random mutagenesis broadens the scope for application in the fine chemical industry, but also in the field of biodegradation. In many cases, these catalysts need to be exploited in whole cell bioconversions or in fermentations, calling for system-wide approaches to understanding strain physiology and metabolism and rational approaches to the engineering of whole cells as they are increasingly put forward in the area of systems biotechnology and synthetic biology.[4]

See also

References

  1. Ashauer, R; Hintermeister, A; O'Connor, I; Elumelu, M, et al. (2012): Significance of Xenobiotic Metabolism for Bioaccumulation Kinetics of Organic Chemicals in Gammarus pulex. Environ. Sci. Technol. in press. http://dx.doi.org/10.1021/es204611h
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