''Cunninghamella elegans'' is a species of

fungus A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from th ...

in the genus ''

Cunninghamella Cunninghamella is a genus of fungi in the order Mucorales, and the family Cunninghamellaceae. The genus was circumscribed by French mycologist Alphonse Louis Paul Matruchot in Ann. Mycol. Vol.1 on page 47 in 1903. The genus name of ''Cunning ...

'' found in soil. It can be grown in Sabouraud dextrose broth, a liquid medium used for cultivation of yeasts and molds from liquid which are normally sterile. As opposed to '' C. bertholletiae'', it is not a

human pathogen A human pathogen is a pathogen (microbe or microorganism such as a virus, bacterium, prion, or fungus) that causes disease in humans. The human physiological defense against common pathogens (such as ''Pneumocystis'') is mainly the responsibility ...

, with the exception of two documented patients.

Description

''Cunninghamella elegans'' is a filamentous fungus that produces purely gray colonies. Electron microscopy studies show that the

conidia A conidium ( ; ), sometimes termed an asexual chlamydospore or chlamydoconidium (), is an asexual, non-motile spore of a fungus. The word ''conidium'' comes from the Ancient Greek word for dust, ('). They are also called mitospores due to the ...

are covered with spines.

Use as a fungal organism capable of xenobiotics metabolism

''Cunninghamella elegans'' is able to degrade

xenobiotic A xenobiotic is a chemical substance found within an organism that is not naturally produced or expected to be present within the organism. It can also cover substances that are present in much higher concentrations than are usual. Natural compo ...

s. It has a variety of enzymes of phases I (modification enzymes acting to introduce reactive and polar groups into their substrates) and II (conjugation enzymes) of the

xenobiotic metabolism Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set of ...

, as do mammals.

Cytochrome P450 monooxygenase Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compo ...

, aryl sulfotransferase,

glutathione S-transferase Glutathione ''S''-transferases (GSTs), previously known as ligandins, are a family of eukaryotic and prokaryotic phase II metabolic isozymes best known for their ability to catalyze the conjugation of the reduced form of glutathione (GSH) to x ...

UDP-glucuronosyltransferase Uridine 5'-diphospho-glucuronosyltransferase ( UDP-glucuronosyltransferase, UGT) is a microsomal glycosyltransferase () that catalyzes the transfer of the glucuronic acid component of UDP-glucuronic acid to a small hydrophobic molecule. This is ...

, UDP-glucosyltransferase activities have been detected in cytosolic or microsomal fractions.

Cytochrome P-450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compo ...

and cytochrome P-450 reductase in ''C. elegans'' are part of the phase I enzymes. They are induced by the corticosteroid

cortexolone 11-Deoxycortisol, also known as cortodoxone (INN), cortexolone as well as 17α,21-dihydroxyprogesterone or 17α,21-dihydroxypregn-4-ene-3,20-dione, is an endogenous glucocorticoid steroid hormone, and a metabolic intermediate towards cortisol. It ...

and by

phenanthrene Phenanthrene is a polycyclic aromatic hydrocarbon (PAH) with formula C14H10, consisting of three fused benzene rings. It is a colorless, crystal-like solid, but can also appear yellow. Phenanthrene is used to make dyes, plastics and pesticides, e ...

. ''C. elegans'' also possesses a

lanosterol 14-alpha demethylase Lanosterol 14α-demethylase (CYP51A1) is the animal version of a cytochrome P450 enzyme that is involved in the conversion of lanosterol to 4,4-dimethylcholesta-8(9),14,24-trien-3β-ol. The cytochrome P450 isoenzymes are a conserved group of pr ...

, another enzyme in the cytochrome P450 family. ''Cunninghamella elegans'' also possesses a

Use as a fungal model organism of mammalian drug metabolism

''Cunninghamella elegans'' is a microbial

model A model is an informative representation of an object, person or system. The term originally denoted the Plan_(drawing), plans of a building in late 16th-century English, and derived via French and Italian ultimately from Latin ''modulus'', a mea ...

of mammalian drug metabolism. The use of this fungus could reduce the over-all need for

laboratory animal Animal testing, also known as animal experimentation, animal research, and ''in vivo'' testing, is the use of non-human animals in experiments that seek to control the variables that affect the behavior or biological system under study. This ...

s. ''Cunninghamella elegans'' is able to transform the tricyclic antidepressants

amitriptyline Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant primarily used to treat cyclic vomiting syndrome (CVS), major depressive disorder and a variety of pain syndromes from neuropathic pain to fibromyalgi ...

and

doxepin Doxepin is a medication falling in the tricyclic antidepressant (TCA) class used to treat major depressive disorder, anxiety disorders, chronic hives, and insomnia. For label updates seFDA index page for NDA 022036/ref> For hives it is a less pre ...

, the tetracyclic antidepressant

mirtazapine Mirtazapine, sold under the brand name Remeron amongst others, is an atypical antidepressant, and as such is used primarily to treat depression. Its effects may take up to four weeks, but can also manifest as early as one to two weeks. It is o ...

, the muscle relaxant

cyclobenzaprine Cyclobenzaprine (sold under the brand name Flexeril, among others) is a medication used for muscle spasms from musculoskeletal conditions of sudden onset. It is not useful in cerebral palsy. It is taken by mouth. Use is not recommended for mor ...

, the typical antipsychotic

chlorpromazine Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar dis ...

as well as the antihistamine and anticholinergic

methdilazine Methdilazine (Dilosyn, Tacaryl) is a first-generation antihistamine with anticholinergic properties of the phenothiazine class. Synthesis See also * Phenothiazine Phenothiazine, abbreviated PTZ, is an organic compound that has the formula ...

and

azatadine Azatadine (Optimine) is a first-generation antihistamine and anticholinergic that was launched by Schering-Plough in 1973. It was patented in 1967. It has been succeeded by both loratadine and desloratadine. and marketing approvals have been ...

. It is also able to transform the antihistamines

brompheniramine Brompheniramine, sold under the brand name Dimetapp among others, is a first-generation antihistamine drug of the propylamine (alkylamine) class. It is indicated for the treatment of the symptoms of the common cold and allergic rhinitis, such as ...

chlorpheniramine Chlorphenamine (CP, CPM), also known as chlorpheniramine, is an antihistamine used to treat the symptoms of allergic conditions such as allergic rhinitis (hay fever). It is taken by mouth. The medication takes effect within two hours and lasts ...

and

pheniramine Pheniramine (trade name Avil among others) is an antihistamine with anticholinergic properties used to treat allergic conditions such as hay fever or urticaria. It has relatively strong sedative effects, and may sometimes be used off-label as an ...

. It forms a

glucoside A glucoside is a glycoside that is derived from glucose. Glucosides are common in plants, but rare in animals. Glucose is produced when a glucoside is hydrolysed by purely chemical means, or decomposed by fermentation or enzymes. The name was o ...

with the diuretic

furosemide Furosemide is a loop diuretic medication used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It may also be used for the treatment of high blood pressure. It can be taken by injection into a vein or by mouth ...

. The transformation of oral contraceptive

mestranol Mestranol, sold under the brand names Enovid, Norinyl, and Ortho-Novum among others, is an estrogen medication which has been used in birth control pills, menopausal hormone therapy, and the treatment of menstrual disorders. It is formulated in c ...

by ''C. elegans'' yields two hydroxylated metabolites, 6beta-hydroxymestranol and 6beta,12beta-dihydroxymestranol.

Metabolism of polycyclic aromatic hydrocarbons

The phase I

cytochrome P450 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...

enzyme systems of ''C. elegans'' has been implicated in the neutralization of numerous

polycyclic aromatic hydrocarbon A polycyclic aromatic hydrocarbon (PAH) is a class of organic compounds that is composed of multiple aromatic rings. The simplest representative is naphthalene, having two aromatic rings and the three-ring compounds anthracene and phenanthrene. ...

s (PAH). It can degrade molecules such as

anthracene Anthracene is a solid polycyclic aromatic hydrocarbon (PAH) of formula C14H10, consisting of three fused benzene rings. It is a component of coal tar. Anthracene is used in the Economic production, production of the red dye alizarin and other dyes ...

, 7-methylbenz nthracene and 7-hydroxymethylbenz nthracene,

acenaphthene Acenaphthene is a polycyclic aromatic hydrocarbon (PAH) consisting of naphthalene with an ethylene bridge connecting positions 1 and 8. It is a colourless solid. Coal tar consists of about 0.3% of this compound. Production and reactions Acena ...

, 1- and

2-methylnaphthalene 2-Methylnaphthalene is a polycyclic aromatic hydrocarbon (PAH). On February 22, 2014, NASA announced a greatly upgraded database for detecting and monitoring PAHs, including 2-methylnaphthalene, in the universe. According to NASA scientists, over ...

naphthalene Naphthalene is an organic compound with formula . It is the simplest polycyclic aromatic hydrocarbon, and is a white crystalline solid with a characteristic odor that is detectable at concentrations as low as 0.08 ppm by mass. As an aromati ...

fluorene Fluorene , or 9''H''-fluorene is an organic compound with the formula (C6H4)2CH2. It forms white crystals that exhibit a characteristic, aromatic odor similar to that of naphthalene. It has a violet fluorescence, hence its name. For commercial pu ...

benzo(a)pyrene Benzo 'a''yrene (B''a''P or B ) is a polycyclic aromatic hydrocarbon and the result of incomplete combustion of organic matter at temperatures between and . The ubiquitous compound can be found in coal tar, tobacco smoke and many foods, espec ...

. In the case of phenanthrene, ''C. elegans'' produces a

conjugate of 1-hydroxyphenanthrene (

phenanthrene 1-O-beta-glucose Phenanthrene is a polycyclic aromatic hydrocarbon (PAH) with formula C14H10, consisting of three fused benzene rings. It is a colorless, crystal-like solid, but can also appear yellow. Phenanthrene is used to make dyes, plastics and pesticides, e ...

Metabolism of pesticides

''Cunninghamella elegans'' is also able to degrade the herbicides

alachlor Alachlor is an herbicide from the chloroacetanilide family. It is an odorless, white solid. The greatest use of alachlor is for control of annual grasses and broadleaf weeds in crops. Use of alachlor is illegal in the European Union and no pro ...

metolachlor Metolachlor is an organic compound that is widely used as an herbicide. It is a derivative of aniline and is a member of the chloroacetanilide family of herbicides. It is highly effective toward grasses. Agricultural use Metolachlor was develo ...

and isoproturon as well as the fungicide mepanipyrim.

Metabolism of phenolics

''Cunninghamella elegans'' can be used to study the metabolism of phenols. This type of molecules already have reactive and polar groups comprised within their structure therefore phases I enzymes are less active than phase II (conjugation) enzymes.

Metabolism of flavonoids

; Flavonols In flavonols, an hydroxyl group is available in the 3- position allowing the

glycosylation Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not al ...

at that position. The biotransformation of

quercetin Quercetin is a plant flavonol from the flavonoid group of polyphenols. It is found in many fruits, vegetables, leaves, seeds, and grains; capers, red onions, and kale are common foods containing appreciable amounts of it. It has a bitter flavor a ...

yields three metabolites, including quercetin 3-O-β-D-glucopyranoside, kaempferol 3-O-β-D-glucopyranoside and isorhamnetin 3-O-β-D-glucopyranoside. Glucosylation and O-methylation are involved in the process. ; Flavones In flavones, there is no hydroxyl group available at the 3- position. Conjugation, in the form of

sulfation Sulfation is the chemical reaction that entails the addition of SO3 group. In principle, many sulfations would involve reactions of sulfur trioxide (SO3). In practice, most sulfations are effected less directly. Regardless of the mechanism, the ...

occurs at the 7- or 4'- positions.

Apigenin Apigenin (4′,5,7-trihydroxyflavone), found in many plants, is a natural product belonging to the flavone class that is the aglycone of several naturally occurring glycosides. It is a yellow crystalline solid that has been used to dye wool. S ...

and

chrysin Chrysin, also called 5,7-dihydroxyflavone, is a flavone found in honey, propolis, the passion flowers, ''Passiflora caerulea'' and ''Passiflora incarnata'', and in ''Oroxylum indicum''. It is extracted from various plants, such as the blue passion ...

are also transformed by ''C. elegans'' and produce apigenin 7-sulfate, apigenin 7,4′-disulfate, chrysin 7-sulfate.

Sulfation Sulfation is the chemical reaction that entails the addition of SO3 group. In principle, many sulfations would involve reactions of sulfur trioxide (SO3). In practice, most sulfations are effected less directly. Regardless of the mechanism, the ...

also occurs on

naringenin Naringenin is a flavorless, colorless flavanone, a type of flavonoid. It is the predominant flavanone in grapefruit, and is found in a variety of fruits and herbs. Structure Naringenin has the skeleton structure of a flavanone with three hyd ...

and produces naringenin-7-sulfate. Glucosylation may nevertheless occur but in 3'- position, as happens during the microbial transformation of psiadiarabin and its 6-desmethoxy analogue, 5,3′ dihydroxy-7,2′,4′,5′-tetramethoxyflavone, by ''Cunninghamella elegans'' NRRL 1392 that gives the 3′-glucoside conjugates of the two flavones. ; flavanones As in flavones, there is no hydroxyl groups available at the 3- position for glycosylation in flavanones. Therefore, sulfation occurs at the 7- position. In compounds like 7-methoxylated flavanones like 7-O-methylnaringenin (

sakuranetin Sakuranetin is a flavan-on, the 7-methoxy derivative of naringenin, found in Polymnia fruticosa and rice, where it acts as a phytoalexin against spore germination of ''Pyricularia oryzae''. Glycosides Sakuranin is the 5-O-glucoside of sakuranet ...

demethylation Demethylation is the chemical process resulting in the removal of a methyl group (CH3) from a molecule. A common way of demethylation is the replacement of a methyl group by a hydrogen atom, resulting in a net loss of one carbon and two hydrogen ato ...

followed by

occur.

Metabolism of synthetic phenolics

It is also able to degrade synthetic phenolic compounds like

bisphenol A Bisphenol A (BPA) is a chemical compound primarily used in the manufacturing of various plastics. It is a colourless solid which is soluble in most common organic solvents, but has very poor solubility in water. BPA is produced on an industrial s ...

Metabolism of heterocyclic organic compounds

''Cunninghamella elegans'' can transform the nitrogen containing compound

phthalazine Phthalazine, also called benzo-orthodiazine or benzopyridazine, is a heterocyclic organic compound with the molecular formula C8H6N2. It is isomeric with other naphthyridines including quinoxaline, cinnoline and quinazoline. Synthesis Phthalazi ...

It is also able to oxidize the

organosulfur Organosulfur compounds are organic compounds that contain sulfur. They are often associated with foul odors, but many of the sweetest compounds known are organosulfur derivatives, e.g., saccharin. Nature abounds with organosulfur compounds—sulfur ...

compound

dibenzothiophene Dibenzothiophene (DBT, diphenylene sulfide) is the organosulfur compound consisting of two benzene rings fused to a central thiophene ring. It is a colourless solid that is chemically somewhat similar to anthracene. This tricyclic heterocycle, and ...

Uses in biotechnology

Methods for efficient ''C. elegans'' genomic DNA isolation and transformation have been developed. The cytochrome P450 of ''C. elegans'' has been cloned in ''

Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...

'' as well as an

enolase Phosphopyruvate hydratase, usually known as enolase, is a metalloenzyme () that catalyses the conversion of 2-phosphoglycerate (2-PG) to phosphoenolpyruvate (PEP), the ninth and penultimate step of glycolysis. The chemical reaction is: :2-p ...

Use in bioconversion

Techniques employed

''Cunninghamella elegans'' can be grown in stirred tank batch bioreactor.

Protoplast Protoplast (), is a biological term coined by Hanstein in 1880 to refer to the entire cell, excluding the cell wall. Protoplasts can be generated by stripping the cell wall from plant, bacterial, or fungal cells by mechanical, chemical or enzy ...

s cultures have been used. (French)

Examples of uses

''Cunninghamella elegans'' can be used for

bioconversion or for

steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...

transformation. It has been used to produce isoapocodeine from 10,11-dimethoxyaporphine, triptoquinone from the synthetic abietane diterpene triptophenolide or for the rational and economical bioconversion of antimalarial drug

artemisinin Artemisinin () and its semisynthetic derivatives are a group of drugs used in the treatment of malaria due to ''Plasmodium falciparum''. It was discovered in 1972 by Tu Youyou, who shared the 2015 Nobel Prize in Physiology or Medicine for her dis ...

to 7beta-hydroxyartemisinin.

Environmental biotechnology

''Cunninghamella elegans'' has been used in

environmental biotechnology Environmental biotechnology is biotechnology that is applied to and used to study the natural environment. Environmental biotechnology could also imply that one try to harness biological process for commercial uses and exploitation. The Internat ...

for the treatment of textile

wastewater Wastewater is water generated after the use of freshwater, raw water, drinking water or saline water in a variety of deliberate applications or processes. Another definition of wastewater is "Used water from any combination of domestic, industr ...

s, for instance those discoloured by

azo dye Azo dyes are organic compounds bearing the functional group R−N=N−R′, in which R and R′ are usually aryl and substituted aryl groups. They are a commercially important family of azo compounds, i.e. compounds containing the C-N=N ...

s or

malachite green Malachite green is an organic compound that is used as a dyestuff and controversially as an antimicrobial in aquaculture. Malachite green is traditionally used as a dye for materials such as silk, leather, and paper. Despite its name the dye is ...

Chitin Chitin ( C8 H13 O5 N)n ( ) is a long-chain polymer of ''N''-acetylglucosamine, an amide derivative of glucose. Chitin is probably the second most abundant polysaccharide in nature (behind only cellulose); an estimated 1 billion tons of chit ...

and

chitosan Chitosan is a linear polysaccharide composed of randomly distributed β-(1→4)-linked Glucosamine, D-glucosamine (deacetylated unit) and N-Acetylglucosamine, ''N''-acetyl-D-glucosamine (acetylated unit). It is made by treating the chitin shell ...

isolated from ''C. elegans'' can be used for heavy metal

biosorption Biosorption is a physiochemical process that occurs naturally in certain biomass which allows it to passively concentrate and bind contaminants onto its cellular structure. Biosorption can be defined as the ability of biological materials to accumul ...

. Production can be made on yam bean (''

Pachyrhizus erosus ''Pachyrhizus erosus'', commonly known as jícama ( or ; Spanish ''jícama'' ; from Nahuatl ''xīcamatl'', ) Mexican turnip, is the name of a native Mexican vine, although the name most commonly refers to the plant's edible tuberous root. Jícam ...

'' L. Urban) medium.

Strains

''Cunninghamella elegans'' ATCC 9245
''Cunninghamella elegans'' ATCC 36112
''Cunninghamella elegans'' ATCC 26269
''Cunninghamella elegans'' NRRL 1393
''Cunninghamella elegans'' IFM 46109
''Cunninghamella elegans'' UCP 542

References

External links

''Cunninghamella elegans'' on the Fungal Genomics Project
{{Taxonbar, from=Q5194357 Cunninghamellaceae Fungi described in 1907 Fungal models Biotechnology Alternatives to animal testing