Use as a fungal organism capable of xenobiotics metabolism Cunninghamella elegans




1 use fungal organism capable of xenobiotics metabolism

1.1 use fungal model organism of mammalian drug metabolism
1.2 metabolism of polycyclic aromatic hydrocarbons
1.3 metabolism of pesticides
1.4 metabolism of phenolics

1.4.1 metabolism of flavonoids
1.4.2 metabolism of synthetic phenolics


1.5 metabolism of heterocyclic organic compounds





use fungal organism capable of xenobiotics metabolism

cunninghamella elegans able degrade xenobiotics. has variety of enzymes of phases (modification enzymes acting introduce reactive , polar groups substrates) , ii (conjugation enzymes) of xenobiotic metabolism, mammals. cytochrome p450 monooxygenase, aryl sulfotransferase, glutathione s-transferase, udp-glucuronosyltransferase, udp-glucosyltransferase activities have been detected in cytosolic or microsomal fractions.


cytochrome p-450 , cytochrome p-450 reductase in c. elegans part of phase enzymes. induced corticosteroid cortexolone , phenanthrene. c. elegans possesses lanosterol 14-alpha demethylase, enzyme in cytochrome p450 family.


c. elegans possesses glutathione s-transferase.


use fungal model organism of mammalian drug metabolism

cunninghamella elegans microbial model of mammalian drug metabolism. use of fungus reduce over-all need laboratory animals.


c. elegans able transform tricyclic antidepressants amitriptyline , doxepin, tetracyclic antidepressant mirtazapine, muscle relaxant cyclobenzaprine, typical antipsychotic chlorpromazine antihistamine , anticholinergic methdilazine , azatadine. able transform antihistamines brompheniramine, chlorpheniramine , pheniramine.


it forms glucoside diuretic furosemide.


the transformation of oral contraceptive mestranol c. elegans yields 2 hydroxylated metabolites, 6beta-hydroxymestranol , 6beta,12beta-dihydroxymestranol.


metabolism of polycyclic aromatic hydrocarbons

the phase cytochrome p450 enzyme systems of c. elegans has been implicated in neutralization of numerous polycyclic aromatic hydrocarbons (pah).


it can degrade molecules such anthracene, 7-methylbenz[a]anthracene , 7-hydroxymethylbenz[a]anthracene, phenanthrene, acenaphthene, 1- , 2-methylnaphthalene, naphthalene, fluorene or benzo(a)pyrene.


in case of phenanthrene, c. elegans produces glucoside conjugate of 1-hydroxyphenanthrene (phenanthrene 1-o-beta-glucose).


metabolism of pesticides

c. elegans able degrade herbicides alachlor, metolachlor , isoproturon fungicide mepanipyrim.


metabolism of phenolics

cunninghamella elegans can used study metabolism of phenols. type of molecules have reactive , polar groups comprised within structure therefore phases enzymes less active phase ii (conjugation) enzymes.


metabolism of flavonoids

flavonols

in flavonols, hydroxyl group available in 3- position allowing glycosylation @ position. biotransformation of quercetin yields 3 metabolites, including quercetin 3-o-β-d-glucopyranoside, kaempferol 3-o-β-d-glucopyranoside , isorhamnetin 3-o-β-d-glucopyranoside. glucosylation , o-methylation involved in process.



flavones

in flavones, there no hydroxyl group available @ 3- position. conjugation, in form of sulfation occurs @ 7- or 4 - positions. apigenin , chrysin transformed c. elegans , produce apigenin 7-sulfate, apigenin 7,4′-disulfate, chrysin 7-sulfate.

sulfation occurs on naringenin , produces naringenin-7-sulfate.


glucosylation may nevertheless occur in 3 - position, happens during microbial transformation of psiadiarabin , 6-desmethoxy analogue, 5,3′ dihydroxy-7,2′,4′,5′-tetramethoxyflavone, cunninghamella elegans nrrl 1392 gives 3′-glucoside conjugates of 2 flavones.



flavanones

as in flavones, there no hydroxyl groups available @ 3- position glycosylation in flavanones. therefore, sulfation occurs @ 7- position. in compounds 7-methoxylated flavanones 7-o-methylnaringenin (sakuranetin), demethylation followed sulfation occur.


metabolism of synthetic phenolics

it able degrade synthetic phenolic compounds bisphenol a.


metabolism of heterocyclic organic compounds

c. elegans can transform nitrogen containing compound phthalazine able oxidize organosulfur compound dibenzothiophene.








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