The Power of Blue Cheese

When people hear the word penicillin, they most likely think of the antibiotic. Penicillin is a common antibacterial agent produced by the fungi Penicillium chrysogenum.¹ This particular genus, Penicillium, is also important for the production of several cheeses. A different strain, Penicillium roqueforti, is used to produce the characteristic flavor in blue cheese.² Like its antibiotic producing sibling, P. roqueforti creates unique compounds throughout its life cycle. The function of these compounds ranges from providing a tangy flavor to possibly preventing disease. Interestingly enough, blue cheese actually contains these beneficial compounds, such as andrastins and myophenolic acid.³ Although both molecules have very different functions, with andrastins displaying anticancer properties, and myophenolic acid used in organ transplant patients, their presence in blue cheese is a result of P. roqueforti. Less important than cancer prevention, other P. roqueforti products such as free fatty acids (FFA) and methyl ketones are essential in the production of blue cheese.² While blue cheese itself is not medically significant, it does provide an interesting environment to study the production of byproducts such as andrastins.

Figure 1: Blue Cheese

Blue cheese flavor comes from the mold spores of P. roqueforti, with the end product actually containing veins of mold. (Figure 1) The mold, which is actually a colony of fungus, plays an important role in developing the tangy flavor of the cheese. Just like human cells, fungi digest triglycerides into FFA, which are eventually reduced to methyl ketones.² The presence of FFA and methyl ketones gives blue cheese its distinct, tangy flavor. In order to achieve the ideal flavor, the cheese must have a good balance of FFA and methyl ketones, which is why P. roqueforti is used. P. roqueforti is very efficient at producing methyl ketones, and is used in the production of several blue cheeses including Roquefort. It is the ideal organism because as it grows in cheese, its ability to digest triglycerides increases exponentially. Like an acorn growing into a tree, fungi grow from a small seed like capsule called a spore, into a fruiting body called a mycelium. It's in this mycelium form that P. roqueforti can metabolize free fatty acids into methyl ketones at the ideal rate and produce a consistent flavor.²

The production of delicious blue cheese is not the only use for P. roqueforti, but it is definitely the most popular. Like its penicillin excreting sibling, P. roqueforti produces compounds that can be used medically. The most well-known compound is mycophenolic acid, which can be used during organ transplantations to prevent host rejection.³ As expected, mycophenolic acid can be found in blue cheese, as it is produced by P. roqueforti during growth. Thankfully, the effects of mycophenolic acid won't be observed after consumption of blue cheese, due to its low concentration, which is good news for avid consumers. The presence of myophenolic acid in blue cheese led to the inspection of blue cheese for other P. roqueforti products. This investigation led to the discovery of andrastins in several varieties of blue cheese cultured with P. roqueforti. Andrastins are a very unique molecule because they have only been found within blue cheese and within a laboratory environment.^3,4 (Figure 2) Currently, four andrastins have been identified, A, B, C and D. Andrastin A has garnered the most interest due to its presence in blue cheese and anticancer properties.  However, andrastins have not been shown to eliminate cancer within a patient, but they have been shown to have beneficial effects in laboratory experiments.

Unlike normal cells, cancerous cells divide uncontrollably, which results in tumors. The goal of most anticancer drugs is to prevent this unregulated multiplication, which is why andrastin A is of great interest. Andrastin A has been shown to help inhibit cellular division in cancerous cells, thus possibly slowing tumor growth.³ In addition to inhibiting growth, andrastin A has also been observed to aid in the accumulation of anticancer drugs in abnormal cells. Cancer cells have a unique surface protein that enables them to expel drugs and prevent their demise. Andrastin A is able to inhibit this protein from functioning and enable the drugs to accumulate and destroy the cancerous cells.³ The mechanism by which this occurs is not fully understood, but further research may lead to a new therapy for cancer patients. Further studies of andrastins themselves will also lead to new ideas about their role in the fight against cancer and if they posses other properties beneficially to human health.

The complexity of blue cheese goes far beyond its flavor. A unique organism, P. roqueforti, plays a huge role in the flavor of blue cheese and is also responsible for the production of several very important molecules. Free fatty acids and methyl ketones are produced by P. roqueforti< through the digestion of triglycerides, similarly to our cells after a high fat meal.² While these molecules are essential for the characteristic blue cheese flavor, they are not the most important molecules found in blue cheese. Myophenolic acid, a compound used during organ transplantation and andrastins, a newly discovered molecule with anticancer properties, are also produced by P. roqueforti.³ These molecules are both found in blue cheese, but are also produced by Penicillium strains in culture. Andrastins for example, were originally discovered in culture and later found to be present in blue cheese. The presence of these molecules in blue cheese is interesting because it means that humans have been consuming andrastins for hundreds of years. However, the concentrations of andrastins in cheeses are not currently known, but future research could determine any correlation between high consumption and cancer. It may be too soon to call blue cheese a “super food”, unless you're one who can't resist its tangy bite.

This piece of art submitted by Derek Hersch

References
1. Den Berg M Van, Gidijala L, Kiela J, Bovenberg R, Vander Keli I. Biosynthesis of active pharmaceuticals: β-lactam biosynthesis in filamentous fungi. Biotechnology & genetic engineering reviews. 2010;27:1-32. Available at: http://www.ncbi.nlm.nih.gov/pubmed/21415891
2. Kinsella JE, Hwang DH. Enzymes of Penicillium roqueforti involved in the biosynthesis of cheese flavor. CRC critical reviews in food science and nutrition. 1976;8(2):191-228. Available at: http://www.ncbi.nlm.nih.gov/pubmed/21770
3. Nielsen KF, Dalsgaard PW, Smedsgaard J, Larsen TO. Andrastins A-D, Penicillium roqueforti Metabolites consistently produced in blue-mold-ripened cheese. Journal of agricultural and food chemistry. 2005;53(8):2908-13. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15826038
4. Omura S, Inokoshi J, Uchida R, et al. Andrastins A-C, new protein farnesyltransferase inhibitors produced by Penicillium sp. FO-3929. I. Producing strain, fermentation, isolation, and biological activities. The Journal of antibiotics. 1996;49(5):414-7. Available at: http://www.ncbi.nlm.nih.gov/pubmed/8682716