Medicines from Molds and Yeasts

Molds are fungi that have many uses for biotechnology or medicine discovery. Because molds typically exist as thin mycelial monolayers, with no protective shell, immune system, or mobility, they rely on an ability to synthesize a variety of unusual compounds for survival. Important medicines from molds, such as penicillin and lovastatin were first isolated from fungal cultures.

Antibiotics

Alexander Fleming led the way to the β-lactam antibiotics with the Penicillium mold and penicillin. Cephalosporin, fusafungine, fumagillin, alamethicin, fusidic acid, aphidicolin, cerulenin, brefeldin A, verrucarin A, itaconic acid, aphidicolin, nigrosporin B, eupenifeldin, vermiculine, and citromycin, can be synthesized by molds.



Cholesterol biosynthesis inhibitors

Akira Endo led the way to the statin medications isolating the pravastatin precursor mevastatin from Penicillium. Lovastatin, the first commercial statin, was found in the Aspergillus mold.

Monascus purpureus creates lovastatin, mevastatin, and the simvastatin precursor monacolin J. Zaragozic acids were isolated from ascomycota. Nicotinamide riboside, a cholesterol biosynthesis inhibitor and nootropic, is made by Saccharomyces cerevisiae.



Antifungals

Griseofulvin, caspofungin, strobilurin, azoxystrobin, micafungin, and echinocandins, were discovered in molds. Anidulafungin is a derivative of an Aspergillus metabolite.



Immunosuppressants

Ciclosporin, was discovered in Tolypocladium inflatum. Mizoribine was discovered in Eupenicillium brefeldianum. Mycophenolic acid was discovered in Penicillium stoloniferum. Thermophilic molds were the source of the fingolimod precursor myriocin. Aspergillus synthesizes the immunosuppressant gliotoxin. Subglutinols are immunosuppressants isolated from Fusarium subglutinans.



Anticancer compounds

Paclitaxel is synthesised using Penicillium raistrickii and plant cell fermentation (PCF). Fungi can synthesize other mitotic inhibitors including vinblastine, vincristine, podophyllotoxin, griseofulvin, aurantiamine, oxaline, and neoxaline.

Dideoxyverticillin A, an isolate of marine Penicillium, was used to create dozens of semi-synthetic anticancer compounds. 11,11'-Dideoxyverticillin A, andrastin A, barceloneic acid A, and barceloneic acid B, are farnesyltransferase inhibitors that can be made by Penicillium. 3-O-Methylfunicone, anicequol, duclauxin, and rubratoxin B, are anticancer metabolites of Penicillium. Penicillium is also potential source of the leukemia medicine asparaginase.



Antimalarials

Codinaeopsin, efrapeptins, zervamicins, and antiamoebin, are made by fungi.



Antidiabetic compounds

Aspergillusol A is an α-glucosidase_inhibitor made by Aspergillus. Sclerotiorin is an aldose reductase inhibitor made by Penicillium.

Ergoloids

Aspergillus and Penicillium are potential sources of ergot alkaloid precursors to psychotropic medicines, cafergot, hydergine, dihydroergotamine, methysergide, methylergometrine, nicergoline, lisuride, bromocriptine, cabergoline, pergolide.

Biotechnology

Endophytic fungi are currently used to manufacture paclitaxel.

Endophytic fungi are potential sources of the paclitaxel precursor baccatin III, the docetaxel precursor 10-deacetylbaccatin, vinblastine, vincristine, huperzine A, hypericin, vincamine, chlorogenic acid, diosgenin, and ginkgolide. Endophytic fungi are potential sources of podophyllotoxin and camptothecin, precursors to etoposide, teniposide, topotecan, and irinotecan.

Mycelium can be used to biosynthesize gold nanoparticles and be used as a mycofiltrate to recover gold from electronic waste. Aspergillus can metabolize piceid to resveratrol. The introduction and expression of the fungal gene responsible for synthesizing baccatin III in the macrofungus Flammulina velutipes was recently reported.



Yeasts

Saccharomyces is used industrially to produce the amino acid lysine, as well as recombinant proteins insulin and Hepatitis B surface antigen. Transgenic yeast can be used to produce artemisinin, hydrocortisone, and a number of insulin analogs. Candida is used industrially to produce vitamins ascorbic acid and riboflavin. Aspergillus niger is used to produce the recombinant protein phytase. Pichia is used to produce the amino acid tryptophan and the vitamin pyridoxine. Rhodotorula is used to produce the amino acid phenylalanine. Moniliella is used industrially to produce the sugar alcohol erythritol. Transgenic yeast can synthesize benzylisoquinoline opioid precursors, as well as convert said precursors to morphine, although a full biosynthetic pathway has yet to be demonstrated. The first synthetic chromosome produced by yeast was reported in 2014.



Vitamin D

The UV-induced biosynthesis of hormone "vitamin D", is practically the same in people and fungi. There are minor chemical differences between kingdoms however, causing people to produce vitamin D3, while fungi produce D2. Plants cannot create this hormone directly. In addition to vitamin D2, fungi synthesize D1 (lumisterol) and D4 (22-dihydroergocalciferol).