Fungal isolates have been researched for decades. Because

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

often exist in thin

mycelial Mycelium (plural mycelia) is a root-like structure of a fungus consisting of a mass of branching, thread-like hyphae. Fungal colonies composed of mycelium are found in and on soil and many other substrates. A typical single spore germinates in ...

monolayers, with no protective shell,

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as Tumor immunology, cancer cells and objects such ...

, and limited mobility, they have developed the ability to synthesize a variety of unusual compounds for survival. Researchers have discovered fungal isolates with anticancer,

antimicrobial An antimicrobial is an agent that kills microorganisms or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals ...

immunomodulatory Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...

, and other

bio-active In pharmacology, biological activity or pharmacological activity describes the beneficial or adverse effects of a drug on living matter. When a drug is a complex chemical mixture, this activity is exerted by the substance's active ingredient or ...

properties. The first

statins Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs. Lo ...

β-Lactam antibiotic β-lactam antibiotics (beta-lactam antibiotics) are antibiotics that contain a beta-lactam ring in their chemical structure. This includes penicillin derivatives ( penams), cephalosporins and cephamycins ( cephems), monobactams, carbapenems and ...

s, as well as a few important antifungals, were discovered in fungi.

Chemotherapeutic isolates

BMS manufactures

paclitaxel Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical can ...

using ''Penicillium'' and plant cell fermentation. Fungi can synthesize

podophyllotoxin Podophyllotoxin (PPT) is the active ingredient in Podofilox, which is a medical cream that is used to treat genital warts and molluscum contagiosum. It is not recommended in HPV infections without external warts. It can be applied either by a hea ...

and

camptothecin Camptothecin (CPT) is a topoisomerase inhibitor. It was discovered in 1966 by M. E. Wall and M. C. Wani in systematic screening of natural products for anticancer drugs. It was isolated from the bark and stem of '' Camptotheca acuminata'' (Campt ...

, precursors to

etoposide Etoposide, sold under the brand name Vepesid among others, is a chemotherapy medication used for the treatments of a number of types of cancer including testicular cancer, lung cancer, lymphoma, leukemia, neuroblastoma, and ovarian cancer. It is ...

teniposide Teniposide (trade name Vumon) is a chemotherapeutic medication used in the treatment of childhood acute lymphocytic leukemia (ALL), Hodgkin's lymphoma, certain brain tumours, and other types of cancer. It is in a class of drugs known as podophyll ...

topotecan Topotecan, sold under the brand name Hycamtin among others, is a chemotherapeutic agent medication that is a topoisomerase inhibitor. It is a synthetic, water-soluble analog of the natural chemical compound camptothecin. It is used in the for ...

, and

irinotecan Irinotecan, sold under the brand name Camptosar among others, is a medication used to treat colon cancer, and small cell lung cancer. For colon cancer it is used either alone or with fluorouracil. For small cell lung cancer it is used with cispl ...

. Lentinan, PSK, and PSP, are registered anticancer immunologic adjuvants. Irofulven and

acylfulvene Acylfulvene is a class of cytotoxic semi-synthetic derivatives of illudin, a natural product that can be extracted from the jack o'lantern mushroom ''(Omphalotus olearius)''. One important acylfulvene, 6-hydroxymethylacylfulvene (irofulven), has ...

are anticancer derivatives of

illudin S The illudins are a family of sesquiterpenes with antitumor antibiotic properties produced by some mushrooms. In their isolated form, illudins show selective toxicity for myelocytic leukemia and other carcinoma cells. Illudins are highly toxic, wit ...

Clavaric acid Clavaric acid is a triterpenoid produced by the mushroom ''Hypholoma sublateritium''. Clavaric acid was discovered by Merck Research Laboratories Merck & Co., Inc. is an American multinational pharmaceutical company headquartered in Rahway, ...

is a reversible farnesyltransferase inhibitor. ''Inonotus obliquus'' creates

betulinic acid Betulinic acid is a naturally occurring pentacyclic triterpenoid which has antiretroviral, antimalarial, and anti-inflammatory properties, as well as a more recently discovered potential as an anticancer agent, by inhibition of topoisomerase. It ...

precursor

betulin Betulin is an abundant, naturally occurring triterpene. It is commonly isolated from the bark of birch trees. It forms up to 30% of the dry weight of silver birch bark. It is also found in birch sap. ''Inonotus obliquus'' and red alder also c ...

. ''Flammulina velutipes'' creates

asparaginase Asparaginase is an enzyme that is used as a medication and in food manufacturing. As a medication, L-asparaginase is used to treat acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). It is given by injection into a vein, muscl ...

. Plinabulin is a fungal isolate derivative currently being researched for anticancer applications.

Cholesterol inhibitors

The statins

lovastatin Lovastatin, sold under the brand name Mevacor among others, is a statin medication, to treat high blood cholesterol and reduce the risk of cardiovascular disease. Its use is recommended together with lifestyle changes. It is taken by mouth. ...

mevastatin Mevastatin (compactin, ML-236B) is a hypolipidemic agent that belongs to the statins class. It was isolated from the mold ''Penicillium citrinum'' by Akira Endo in the 1970s, and he identified it as a HMG-CoA reductase inhibitor, i.e., a stat ...

, and

simvastatin Simvastatin, sold under the brand name Zocor among others, is a statin, a type of lipid-lowering medication. It is used along with exercise, diet, and weight loss to decrease elevated lipid levels. It is also used to decrease the risk of hea ...

precursor monacolin J, are fungal isolates. Additional fungal isolates that inhibit cholesterol are zaragozic acids, eritadenine, and

nicotinamide riboside Nicotinamide riboside (NR, SR647) is a pyridine-nucleoside and a form of vitamin B3, functioning as a precursor to nicotinamide adenine dinucleotide or NAD+. Chemistry While the molecular weight of nicotinamide riboside is 255.25 g/mol, that o ...

Immunosuppressants

Ciclosporin Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's diseas ...

mycophenolic acid Mycophenolic acid (MPA) is an immunosuppressant medication used to prevent rejection following organ transplantation and to treat autoimmune conditions such as Crohn's disease and lupus. Specifically it is used following kidney, heart, and liv ...

mizoribine Mizoribine (INN, trade name Bredinin) is an immunosuppressive drug. The compound was first observed in Tokyo, Japan Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwes ...

, FR901483, and gliotoxin, are immunosuppressant fungal isolates.

Antimicrobials

Penicillin Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using ...

cephalosporin The cephalosporins (sg. ) are a class of β-lactam antibiotics originally derived from the fungus '' Acremonium'', which was previously known as ''Cephalosporium''. Together with cephamycins, they constitute a subgroup of β-lactam antibioti ...

s, fusafungine,

usnic acid Usnic acid is a naturally occurring dibenzofuran derivative found in several lichen species with the formula C18H16O7. It was first isolated by German scientist W. Knop in 1844 and first synthesized between 1933-1937 by Curd and Robertson. Usnic a ...

, fusidic acid, fumagillin,

brefeldin A Brefeldin A is a lactone antiviral produced by the fungus ''Penicillium brefeldianum''. Brefeldin A inhibits protein transport from the endoplasmic reticulum to the golgi complex indirectly by preventing association of COP-I coat to the Golgi m ...

verrucarin A Verrucarin A is a chemical compound that belongs in the class of trichothecenes, a group of sesquiterpene toxins produced by several fungi, namely from the ''Fusarium'' species, that are responsible for infecting food grains. It was first describe ...

, alamethicin, are antibiotic fungal isolates. Antibiotics retapamulin, tiamulin, and valnemulin are derivatives of the fungal isolate pleuromutilin.

Griseofulvin Griseofulvin is an antifungal medication used to treat a number of types of dermatophytoses (ringworm). This includes fungal infections of the nails and scalp, as well as the skin when antifungal creams have not worked. It is taken by mouth. ...

echinocandin Echinocandins are a class of antifungal drugs that inhibit the synthesis of β-glucan in the fungal cell wall via noncompetitive inhibition of the enzyme 1,3-β glucan synthase. The class has been termed the "penicillin of antifungals," along ...

strobilurin Strobilurins are a group of natural products and their synthetic analogs. A number of strobilurins are used in agriculture as fungicides. They are part of the larger group of QIs (Quinone outside Inhibitors), which act to inhibit the respiratory ...

azoxystrobin Azoxystrobin is the ISO common name for an organic compound that is used as a fungicide. It is a broad spectrum systemic active ingredient widely used in agriculture to protect crops from fungal diseases. It was first marketed in 1996 using the ...

caspofungin Caspofungin ( INN) (brand name Cancidas) is a lipopeptide antifungal drug from Merck & Co., Inc. discovered by James Balkovec, Regina Black and Frances A. Bouffard. It is a member of a new class of antifungals termed the echinocandins. It wor ...

micafungin Micafungin, sold under the brand name Mycamine, is an echinochandin antifungal medication used to treat and prevent invasive fungal infections including candidemia, abscesses, and esophageal candidiasis. It inhibits the production of beta-1,3-g ...

, are fungal isolates with antifungal activity.

Psychotropic isolates

The headache medications

cafergot Caffeine/ergotamine (trade name Cafergot) is the proprietary name of a medication consisting of ergotamine tartrate and caffeine. This combination is used for the treatment of headaches, such as migraine headache. Use Correct timing of use i ...

, dihydroergotamine, methysergide,

methylergometrine Methylergometrine, also known as methylergonovine and sold under the brand name Methergine, is a medication of the ergoline and lysergamide groups which is used as an oxytocic in obstetrics and in the treatment of migraine. It reportedly produce ...

, the dementia medications

hydergine Ergoloid mesylates ( USAN), co-dergocrine mesilate (BAN) or dihydroergotoxine mesylate, trade name Hydergine, is a mixture of the methanesulfonate salts of three dihydrogenated ergot alkaloids (dihydroergocristine, dihydroergocornine, and alp ...

, nicergoline, the Parkinson's disease medications

lisuride Lisuride, sold under the brand name Dopergin among others, is a monoaminergic medication of the ergoline class which is used in the treatment of Parkinson's disease, migraine, and high prolactin levels. It is taken by mouth. Side effects of lis ...

bromocriptine Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic mali ...

cabergoline Cabergoline, sold under the brand name Dostinex among others, is a dopaminergic medication used in the treatment of high prolactin levels, prolactinomas, Parkinson's disease, and for other indications. It is taken by mouth. Cabergoline is an er ...

, and

pergolide Pergolide, sold under the brand name Permax and Prascend (veterinary) among others, is an ergoline-based dopamine receptor agonist used in some countries for the treatment of Parkinson's disease. Parkinson's disease is associated with reduced d ...

were all derived from ''

Claviceps Ergot ( ) or ergot fungi refers to a group of fungi of the genus ''Claviceps''. The most prominent member of this group is '' Claviceps purpurea'' ("rye ergot fungus"). This fungus grows on rye and related plants, and produces alkaloids that ca ...

'' isolates. '' Polyozellus multiplex'' synthesizes prolyl endopeptidase inhibitors polyozellin, thelephoric acid, and

kynapcin Skeletal formula of kynapcin-24 Kynapcin is a general name for a number of dibenzofuranyl derivatives of the molecule polyozellin, present in the fungus ''Polyozellus multiplex''. Like polyozellin, some kynapcins inhibit prolyl endopeptidase, a ...

s. '' Boletus badius'' synthesizes L-theanine.

Other isolates

150px Researchers have discovered other interesting fungal isolates like the antihyperglycemic compounds ternatin, aspergillusol A, sclerotiorin, and antimalarial compounds

codinaeopsin Codinaeopsin is an antimalarial isolated from a fungal isolate found in white yemeri trees (''Vochysia guatemalensis'') in Costa Rica. It is reported to have bioactivity against ''Plasmodium falciparum'' with an IC50 = 2.3 μg/mL (4.7 ...

efrapeptin Efrapeptins are peptides produced by fungi in the genus '' Tolypocladium'' that have antifungal, insecticidal, and mitochondrial ATPase inhibitory activities. They are produced via a biosynthetic pathway similar to but simpler than the Ciclosporin ...

s, and

antiamoebin Antiamoebin is an anti-microbial/protozoa Protozoa (singular: protozoan or protozoon; alternative plural: protozoans) are a group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microo ...

. The fungal isolate

ergothioneine Ergothioneine is a naturally occurring amino acid and is a thiourea derivative of histidine, containing a sulfur atom on the imidazole ring. This compound occurs in relatively few organisms, notably actinomycetota, cyanobacteria, and certain fun ...

is actively absorbed and concentrated by the human body via

SLC22A4 Solute carrier family 22, member 4, also known as SLC22A4, is a human gene; the encoded protein is known as the ergothioneine transporter. Function The encoded protein is an integral protein of the plasma membrane containing 12 transmembrane s ...

. Other notable fungal isolates include vitamin D₁, vitamin D₂, and vitamin D₄.

References

{{Reflist

External links

Bioprospecting for Microbial Endophytes and Their Natural Products – 2003
Pharmaceutical isolates Fungi and humans

Chemotherapeutic isolates

Cholesterol inhibitors

Immunosuppressants

Antimicrobials

Psychotropic isolates

Other isolates

See also

References

External links