Medicines from Fungi: Penicillin, Lovastatin and Cyclosporine
Many people are familiar with fungi in the form of molds and mushrooms. People may not realize that fungi can be a source of medicinal chemicals, however. The fuzzy growth on a forgotten sandwich, the mold on a decaying piece of fruit, cultivated mushrooms bought in a grocery store and mushrooms harvested from the wild may all contain useful medicines for health problems.
Penicillin is probably the best known medication made by a mold, but there are many other examples. Penicillin is an antibiotic and kills bacteria. Another medication made by a mold is lovastatin, which is used to lower LDL cholesterol (the so-called bad cholesterol). Cyclosporine is a mold chemical that suppresses the activity of the immune system and is administered after an organ transplant to help prevent rejection of the organ. It's also used to treat some autoimmune diseases.
Some mushrooms have medicinal benefits, too. Oyster mushrooms contain lovastatin, for example, and shiitake mushrooms contain lentinan and eritadenine. Lentinan is an interesting substance that may boost the activity of the immune system and make medications used to treat some types of cancer more effective. Eritadenine lowers blood cholesterol In animals and may do the same in humans.
What is a Mold?
The word "mold" (or mould) is very commonly used but is actually a non-scientific term. It generally refers to fungi with a fuzzy, hairy or powdery appearance that grow where they're not wanted and don't produce mushrooms.
Many medicinal chemicals obtained from fungi are produced by molds. Like other fungi (except for yeasts), the body of a mold consists of branching, thread-like structures called hyphae. The hyphae of a fungus collectively form a structure known as a mycelium. The mycelium may be partially or completely hidden in the substrate of the fungus.
Molds produce small reproductive structures that bear spores. The spores produce a powdery appearance on top of the hyphae and may sometimes be colored. Unlike some other fungi, molds don't produce mushrooms, which are larger, more noticeable and more complex reproductive structures.
Molds and other fungi can't make their own food and must obtain it from their environment. They secrete digestive enzymes into their food source and then absorb the products of the digestion.
The Discovery of Penicillin
Penicillin was the first antibiotic to be identified. It was discovered by a Scottish biologist named Alexander Fleming. The discovery began a wonderful period in which previously deadly infections could be cured. In the present time not all antibiotics are as effective as they once were due to the growing problem of bacterial resistance.
In 1928, Fleming was studying bacteria known as staphylococci. He went on vacation, leaving petri dishes containing the bacteria in his lab. When he returned he saw that many of the dishes had been contaminated with airborne fungal spores and now had fungi growing in them. Fleming noticed that there was a clear zone around the fungus in one dish. He suspected that the fungus had made a substance that had killed the bacteria. Eventually, with the aid of other scientists, he was able to isolate penicillin from the dish and show that it could indeed kill bacteria.
Alexander Fleming's Discovery of Penicillin
The Penicillium Fungus
Several species of Penicillium make penicillin. There is some controversy about the identity of the fungus in Fleming's petri dishes. It may have been Penicillium chrysogenum, also known as Penicillium notatum, which is a common indoor mold.
The hyphae of Penicillium bear reproductive structures called conidiophores. The top of each conidiophore is branched, making it look like a broom. Each branch bears a chain of spores known as conidia. The conidia of Penicillium chrysogenum are blue to blue-green in color. They are shed into the air and are transported by air currents to new areas. If they land on a suitable food source (such as the nutrient material in Fleming's petri dish) they will grow into a new mycelium.
How Does Penicillin Work?
Penicillin kills bacteria by preventing them from making a cell wall, which is the outer covering of a bacterium. It does this by preventing cross links from forming between the peptidoglycan molecules in the wall.
As a bacterial cell grows, it makes new cell wall to accommodate its increased size. In the presence of penicillin, a gap forms in the wall as the cell enlarges, since no new wall material can be made. The cell contents leak out of their container and the cell dies.
Lovastatin is made by a mold called Aspergillus terreus. The fungus can be found around the world, but it usually inhabits tropical areas. It's a decomposer that normally lives in soil. It can also appear in other habitats, such as stored grains, dried fruit and spices, air conditioners and dust. Like Penicillium, it produces conidiophores that bear conidia.
Aspergillus terreus is a useful mold. It provides us with both lovastatin and organic acids. Like some other fungi, however, Aspergillus terreus can hurt us as well as help us. The fungus can cause disease in humans. It can produce a skin infection and a potentially serious illness called aspergillosis. If the fungus enters the lungs but progresses no further into the body, the infection can generally be treated successfully. If the fungus penetrates deeper into the body, however, the illness is much harder to treat.
LDL Cholesterol, HDL Cholesterol and Lovastatin
Two important forms of cholesterol are LDL cholesterol and HDL cholesterol. The cholesterol molecules in these two substances are actually the same. In LDL cholesterol low density lipoproteins are attached to the cholesterol while in HDL cholesterol high density lipoproteins are joined to the cholesterol.
LDL cholesterol is known as the bad cholesterol, even though it plays an essential role in the body. It travels away from the liver, where it's made, in order to provide cells with the essential cholesterol molecules that they need for their cell membrane. If too much LDL cholesterol is present in the blood, cholesterol may be deposited in the lining of arteries, joining with other substances to form a material called plaque. The plaque increases the risk of a heart attack, a stroke and peripheral artery disease. HDL cholesterol is known as the good cholesterol because it removes cholesterol from the arteries and takes it to the liver to be broken down.
The best medications for solving a cholesterol problem lower LDL cholesterol and either don't affect HDL cholesterol or, like lovastatin, actually cause it to increase. (There is some debate about the consistency and size of this increase.) Lovastatin blocks a liver enzyme called HMG-CoA reductase that is needed in the production of cholesterol. This reduces the amount of cholesterol in the blood.
How to Prevent and Reduce High Cholesterol
The oyster mushroom is another fungus that makes lovastatin. The scientific name of the mushroom is Pleurotus ostreatus. It's a popular food item and is available in many supermarkets. The mushroom is widely cultivated but also grows in the wild. It's usually white to light brown in color. Its stalk is often strongly curved to one side.
In the wild, oyster mushrooms grow on tree trunks, branches or fallen logs. They decompose the wood in these items as they grow, absorbing its nutrients. Although they depend mainly on decaying wood for food, oyster mushrooms are also carnivorous. The mycelium secretes drops of poison that kill worm-like creatures called nematodes which are present in wood. The fungus releases digestive enzymes into the worms and then absorbs the products of the digestion. It's thought that the nematodes provide the fungus with the nitrogen that the wood lacks.
Using Medicinal Chemicals in Plants
When a medicinal chemical is found in a plant, the chemical is often extracted, purified and concentrated before it's used as a medication. In some cases, once the natural chemical and its production are studied, scientists are able to create it in the laboratory and use the lab version as a medicine.
Some plants contain a sufficient concentration of a medicinal chemical to be useful when the plant is eaten as food. Oyster mushrooms may be one of these plants. Researchers have found that the mushrooms contain up to 2.8% lovastatin by dry weight. This may be sufficient to be medically supportive for a cholesterol problem that is being primarily treated by other methods. Unfortunately, we don't know the actual concentration of lovastatin in the oyster mushrooms that we buy.
Cultivated Oyster Mushroom Time lapse
Lovastatin in Oyster Mushrooms
Lovastatin has been shown to be a very effective medication for lowering a high blood cholesterol level (hypercholesterolemia). However, people with hypercholesterolemia generally take prescribed lovastatin tablets instead of relying on the lower concentration of the medication found in oyster mushrooms.
Animal experiments have shown that eating powdered oyster mushrooms does lower cholesterol, but the mushrooms are given to the animals in larger doses than people would normally eat. For example, one experiment showed that when oyster mushroom powder formed 10% of the diet in rabbits, their blood cholesterol level was reduced by 65%. Similarly, when oyster mushrooms formed 5% of the diet in rats, their blood cholesterol level was reduced by 31% to 46%.
Making oyster mushrooms such a large component of a human diet may not be appropriate. Adding a moderate intake of the mushrooms to a healthy diet might be helpful for someone with only a minor elevation in cholesterol level, though, as long as they haven't been prescribed a medication by their doctor. If the person is taking lovastatin or another statin drug, they should ask their doctor about the advisability of eating oyster mushrooms.
Cyclosporine or Ciclosporin
Cyclosporine was discovered in 1969. It's produced by a soil mold called Tolypocladium inflatum. In 1996 it was discovered that this mold is actually a stage in the life of a fungus known as Cordyceps subsessilis, which is a parasite of beetles. The soil stage of the fungus is much more common than the parasitic stage.
Cyclosporine is an immunosuppressant. It decreases the activity of the immune system, reducing the probability that it will attack and destroy an organ or tissue coming from another person. The immune system normally protects us from cells and particles that don't belong in our body. By preventing the immune system from doing its job in the case of a transplant, cyclosporine is a potential life-saver. There is a drawback to the drug, however. While taking the medication a patient may be more susceptible to infections because their immune system is hampered.
Cyclosporine is also prescribed for some cases of psoriasis, rheumatoid arthritis, Crohn's disease and ulcerative colitis, especially when these conditions haven't responded to other treatments. These are all autoimmune disorders, conditions in which the immune system is overactive and mistakenly attacks the body's own tissues. Dampening the response of the immune system can relieve a patient's symptoms.
Shiitake Mushrooms, Lentinan and Eritadenine
Shiitake mushrooms (Lentinula edodes) are edible mushrooms that are native to East Asia and are cultivated in many countries. Two chemicals of interest in shiitake mushrooms are lentinan and eritadenine. Lentinan may boost the immune system, thereby helping to fight cancer and to destroy viruses. Lentinan's active ingredient seems to be a substance called 1,3 beta glucan. Beta glucans in other fungi and in some plants are also thought to have medicinal benefits for humans. Eritadenine may lower cholesterol in humans, as it does in animals.
According to the Memorial Sloan-Kettering Cancer Center:
- A few clinical trials show that when combined with chemotherapy lentinan increases the survival time of people with certain types of cancer.
- Lab studies and a few human studies show that lentinan boosts the activity of specific cells within the immune system.
- In the lab, lentinan has destroyed viruses and bacteria. Whether it can do this in the human body is unknown.
More investigations are needed to clarify the medicinal effects of shiitake mushrooms and their components. The evidence obtained so far is very interesting.
Discovering New Medicines in Fungi
Many fungal chemicals have improved health problems in lab animals. Some of these chemicals have proved to be effective in us, too. Clinical tests are needed to confirm that others work in humans. Discovering an appropriate dose for a chemical is also essential. As with any medication, a dose that is too low would likely be ineffective, while a dose that is too high could cause dangerous side effects.
The potential for obtaining new medicines from fungi is very exciting. The discovery of a new organism in nature is always interesting, but in the case of fungi it could also be important. There may be effective treatments for serious diseases inside the mycelia and mushrooms of fungi.
References and Further Reading
© 2013 Linda Crampton