Lovastatin is a valuable drug, an inhibitor of 3-hydroxy-3methylglutaryl-coenzyme, a reductase (HMG-CoA reductase), an enzyme that catalyzes the conversion of HMG-CoA to mevalonate. Mevalonate is a required building block for cholesterol biosynthesis and lovastatin interferes with its production by acting as a reversible competitive inhibitor for HMG-CoA, which binds to the HMG-CoA reductase.
Lovastatin is produced by some microorganisms, Aspergillus terreus is usually used in industrial production. There are a lot of papers about the use of lovastatin in medicine and the optimization of its production etc. However, I could not find any info about its role in the producing microorganism. Why does it produce this compound and accumulate it?
Hi, Dear Natalia
Your question is very interesting I will follow given answers.
I think this effect perhaps because of the chemical bonds within fungi. Or maybe some receptors in the surface of fungi cells cause to intract with lipids.
Good Luck
Dear Reza, thanks for your hypotheses... I'm a novice in this field. I asked a person who worked a lot with the production of this compound from A. terreus and with the development of superproducing strains. I was told that the excess of lovastatin is negatively influenced on a cell itself that IMHO indicates the necessity of a kind of a negative feedback regulation of its production. In addition, A. terreus does not excrete lovastatin into the cultural medium. Therefore, it seems that the host cell needs a certain concentration of lovastatin... for which purpose? Even if this is a kind of a by-product - it should either be utilized in some way, or excreted outside the cell, or be used...
If you mean the process of a lovastatin synthesis, then I suppose the answer is "no". Lovastatin biosynthesis starts from acetate units and occurs via a polyketide pathway. The detailed description of this process can be find in the paper "Biotechnological production and application of statins" written by J. Barrioz-Gonzalez and R. Miranda (Appl Microbiol. biotechnol., 2010, 85:869-883). Shortly, among the enzymes, involved into this process, there are two type I polyketide synthases (multidomain enzymes), enoyl reductase, CYP450 oxygenases, and 20methylbutyryl/monakolin J transesterase.
If necessary, I can cite this work with more details or attach the corresponding file (is it permitted here?)
One remark concerning a "chemical weapon": the problem is that lovastatin is NOT excreted by producing cells... not good for a weapon. It has some antimicrobial activity (according to at least one study), but the necessary concentration is rather high, and these researchers used commercial lovastatin preparations to examine this activity.
Dear Natalia, to my modest knowledge lovastatin (secondary metabolite produced by fungi) is excreted from the fungal cells into the medium in the form of beta-hydroxy acid-mevinolinic acid (please see the paper from Casas-Lopez et al., 2003. Enzyme Microb. Technol. 33, 270-277). I agree with above responses about the role of lovastatin as competitive weapon. Prof. Demain has explained in his multiples review articles that statins may play important ecological functions as competitive weapons used against other microorganisms.
Dear Saul, thank you very much! I'll look on the papers you mentioned.
Actually, when I talked about this question with other persons who worked with this compound and its industrial production, I was told that lovastatin is not excreted from fungal cell and, because of this fact, its industrial production is based on the growing of a large amount of mycelium followed by its collection, treatment with a lysing solution, and, finally, isolation of lovastatin.
Therefore, can we consider that the accumulation of lovastatin in fungal cells is explained by the fact that the rate of its transformation into beta-hydroxyl acid form with the subsequent excretion is too low comparing to the rate of its production (and this difference is even more in the case of high-producing strains)?
I still have some questions concerning its "weapon" function, but need to read the papers first...
Meanwhile, for those who is also interested: I found one more article arguing for the role of lovastatin as a "biological weapon" due to its anti-fungal effects:
Antifungal Activity and the Potential Correlation with Statin-Producing Ability: An Optimized Screening Applied to Filamentous Fungi from Las Yungas Subtropical Rainforest
M.E. Cabral, O.D. Delgado, D.A. Sampietro, C.A. Catalan, L.I.C. Figueroa and J.I. Farina
http://scialert.net/qredirect.php?doi=jm.2010.833.848&linkid=pdf
We are accruing more and more evidence that secondary metabolites are produced as fitness 'aids'. They can protect against physical stress (UV), protect against insect attack and provide anti-microbial properties to the producing fungus. Lovastatin has antifungal properties and perhaps helps A. terreus in securing a niche in ecological settings
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