Biotransformation

Biotransformation is the chemical modication (ormodications) made by an organism on a chemical com-pound. If this modication ends in mineral compoundslike CO2, NH4+, or H2O, the biotransformation is calledmineralisation.Biotransformation means chemical alteration of chemi-cals such as (but not limited to) nutrients, amino acids,toxins, and drugs in the body. It is also needed to rendernonpolar compounds polar so that they are not reabsorbedin renal tubules and are excreted. Biotransformation ofxenobiotics can dominate toxicokinetics and the metabo-lites may reach higher concentrations in organisms thantheir parent compounds.[1]

1 Drug metabolismMain article: drug metabolism

Themetabolism of a drug or toxin in a body is an exampleof a biotransformation. The body typically deals with aforeign compound by making it more water-soluble, toincrease the rate of its excretion through the urine. Thereare many dierent processes that can occur; the pathwaysof drug metabolism can be divided into:

phase phase II

Drugs can undergo one of four potential biotransforma-tions: Active Drug to Inactive Metabolite, Active Drugto Active Metabolite, Inactive Drug to Active Metabolite,Active Drug to Toxic Metabolite (biotoxication).

1.1 Phase reaction Includes oxidative, reductive, and hydrolytic reac-tions.

In these type of reactions, a polar group is eitherintroduced or unmasked, so the drug molecule be-comes more water-soluble and can be excreted.

Reactions are non-synthetic in nature and in gen-eral produce a more water-soluble and less activemetabolites.

The majority of metabolites are generated by acommon hydroxylating enzyme system known asCytochrome P450.

1.2 Phase II reaction These reactions involve covalent attachment of smallpolar endogenous molecule such as glucuronic acid,sulfate, or glycine to formwater-soluble compounds.

This is also known as a conjugation reaction.

The nal compounds have a largermolecular weight.

2 Microbial biotransformationBiotransformation of various pollutants is a sustainableway to clean up contaminated environments.[2] Thesebioremediation and biotransformation methods harnessthe naturally occurring, microbial catabolic diversity todegrade, transform or accumulate a huge range of com-pounds including hydrocarbons (e.g. oil), polychlorinatedbiphenyls (PCBs), polyaromatic hydrocarbons (PAHs),pharmaceutical substances, radionuclides and metals.Major methodological breakthroughs in recent yearshave enabled detailed genomic, metagenomic, pro-teomic, bioinformatic and other high-throughput analy-ses of environmentally relevant microorganisms provid-ing unprecedented insights into biotransformation andbiodegradative pathways and the ability of organisms toadapt to changing environmental conditions.Biological processes play a major role in the removal ofcontaminants and pollutants from the environment. Somemicroorganisms possess an astonishing catabolic versa-tility to degrade or transform such compounds. Newmethodological breakthroughs in sequencing, genomics,proteomics, bioinformatics and imaging are producingvast amounts of information. In the eld of Environ-mental Microbiology, genome-based global studies opena new era providing unprecedented in silico views ofmetabolic and regulatory networks, as well as clues to theevolution of biochemical pathways relevant to biotrans-formation and to the molecular adaptation strategies tochanging environmental conditions. Functional genomicand metagenomic approaches are increasing our under-standing of the relative importance of dierent path-ways and regulatory networks to carbon ux in particu-lar environments and for particular compounds and theyare accelerating the development of bioremediation tech-nologies and biotransformation processes.[2] Also thereis other approach of biotransformation called enzymaticbiotransformation.

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3 Oil biodegradationPetroleum oil is toxic for most life forms and episodic andchronic pollution of the environment by oil causes majorecological perturbations. Marine environments are espe-cially vulnerable, since oil spills of coastal regions andthe open sea are poorly containable and mitigation is dif-cult. In addition to pollution through human activities,millions of tons of petroleum enter the marine environ-ment every year from natural seepages. Despite its toxic-ity, a considerable fraction of petroleum oil entering ma-rine systems is eliminated by the hydrocarbon-degradingactivities of microbial communities, in particular by a re-markable recently discovered group of specialists, the so-called hydrocarbonoclastic bacteria (HCB). Alcanivoraxborkumensis, a paradigm of HCB and probably the mostimportant global oil degrader, was the rst to be sub-jected to a functional genomic analysis. This analysis hasyielded important new insights into its capacity for (i) n-alkane degradation including metabolism, biosurfactantproduction and biolm formation, (ii) scavenging of nu-trients and cofactors in the oligotrophic marine environ-ment, as well as (iii) coping with various habitat-specicstresses. The understanding thereby gained constitutes asignicant advance in eorts towards the design of newknowledge-based strategies for the mitigation of ecolog-ical damage caused by oil pollution of marine habitats.HCB also have potential biotechnological applications inthe areas of bioplastics and biocatalysis.[3]

4 Metabolic engineering and bio-catalytic applications

The study of the fate of persistent organic chemicalsin the environment has revealed a large reservoir ofenzymatic reactions with a large potential in prepara-tive organic synthesis, which has already been exploitedfor a number of oxygenases on pilot and even on in-dustrial scale. Novel catalysts can be obtained frommetagenomic libraries and DNA sequence based ap-proaches. Our increasing capabilities in adapting thecatalysts to specic reactions and process requirementsby rational and random mutagenesis broadens the scopefor application in the ne chemical industry, but also inthe eld of biodegradation. In many cases, these cata-lysts need to be exploited in whole cell bioconversionsor in fermentations, calling for system-wide approachesto understanding strain physiology and metabolism andrational approaches to the engineering of whole cells asthey are increasingly put forward in the area of systemsbiotechnology and synthetic biology.[4]

5 See also Microbial biodegradation

Xenobiotic metabolism Biodegradation Bioremediation Mineralisation

6 References[1] Ashauer, R; Hintermeister, A; O'Connor, I; Elumelu, M,

et al. (2012): Signicance of Xenobiotic Metabolismfor Bioaccumulation Kinetics of Organic Chemicals inGammarus pulex. Environ. Sci. Technol. in press.http://dx.doi.org/10.1021/es204611h

[2] Diaz E (editor). (2008). Microbial Biodegradation: Ge-nomics and Molecular Biology (1st ed. ed.). Caister Aca-demic Press. ISBN 978-1-904455-17-2.

[3] Martins VAP et al. (2008). Genomic Insights into OilBiodegradation in Marine Systems. Microbial Biodegra-dation: Genomics and Molecular Biology. Caister Aca-demic Press. ISBN 978-1-904455-17-2.

[4] Meyer A and Panke S (2008). Genomics in MetabolicEngineering and Biocatalytic Applications of the PollutantDegradation Machinery. Microbial Biodegradation: Ge-nomics and Molecular Biology. Caister Academic Press.ISBN 978-1-904455-17-2.

7 External links Biotransformation of Drugs Biodegradation, Bioremediation and Biotransfor-mation

Microbial Biodegradation Biotransformation and Bioaccumulation in freshwa-ter invertebrates

Ecotoxicology & Models

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Drug metabolismPhase reactionPhase II reaction

Microbial biotransformationOil biodegradationMetabolic engineering and biocatalytic applicationsSee alsoReferencesExternal links Text and image sources, contributors, and licensesTextImagesContent license