#lovastatin

(via Statins - Atorvastatin, Rosuvastatin, Simvastatin and Lovastatin)

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The fungus Aspergillus terreus has dominated the biological production of the “crackerjack” drugs known as statins, particularly lovastatin. The aim of this research was the production of lovastatin which is a known cholesterol-lowering drug, through microbial fermentation using A. terreus. Besides, it also aimed to analyze certain bioactive chemical products and evaluation of such antibacterial and antifungal products, if any produced. Bioactive chemical compounds often referred as secondary metabolites were analyzed using the Gas ChromatographyMass Spectroscopy technique (GC-MS) technique. A. terreus is known to produce a vast variety of important secondary metabolites with high biological activities. The isolation of the natural statins such as lovastatin or mevastatin from A. terreus represents one of the great achievements of industrial Microbiology/Fermentation Technology. Here we report the Aspergillus terreus NBRC (IFO) 31217 (Strain I) and ATCC 11877 (Strain II) produce lovastatin and they also produce important bioactive compounds of high commercial value like isovaline (C5H11NO2), 2-oxo-nvaleric acid and silane etc.

Lovastatin (C24H36O5) is a fungal secondary metabolite that inhibits conversion of 3-hydroxy-3- methylglutaryl coenzyme A (HMG CoA) to mevalonate in cholesterol biosynthesis. Lovastatin producing fungus Aspergillus terreus was grown in Solid State Fermentation (SSF) with various agro based wastes and in Submerged Fermentation (SmF) to evaluate the suitable growth medium for maximum production of lovastatin. Eighty three agro based substrates and six different types of SmF media were used for the production. Wheat bran and sprouted wheat were suitable substrates for lovastatin production yielding1.00 mg/G DWS and 1.311 mg/DWS of lovastatin, respectively. None of the SmF medium was found to be suitable for lovastatin production, although all media supported growth of the fungus.

The etiology of benign prostatic hyperplasia (BPH) is still largely unresolved. Multiple partially overlapping and complementary systems (nerve, endocrine, immune, vascular) and local factors are likely to be involved (1), and therefore, several etiologic factors for BPH have been proposed to date (2). Primary interest has been focused on the steroid hormones, especially testosterone estrogen and their metabolites (3). Of the currently used BPH pharmacotherapeutic treatments, only the 5a-reductase inhibitors have been demonstrated to modify the underlying pathology scores and imaging studies (8). The best results have occurred in men with large prostates (> 40 grams), while all the 5a-Reductase Inhibitor’s (5ARI) effect takes approximately 3 to 6 months to occur (9). To our knowledge, of the currently used BPH pharmacotherapeutic interventions only the 5a-RI’s have been shown to modify the underlying pathology.

In an ongoing long-term safety study, 744 patients have received lovastatin for an average duration of 2.5 years up to March 1988. Fifteen patients (2.0%) have been withdrawn because of drug-attributable adverse events: raised transaminases (9), skin rash (2), gastrointestinal symptoms (2), myopathy (1) and insomnia (1). No effect of the drug on the human lens has been observed up to the date mentioned above. Lovastatin has been available in the United States since September 1987. By March 1988, the drug had been prescribed for approximately 250,000 patients. This clinical experience has confirmed the tolerability observed in clinical trials. The good adverse-effect profile of lovastatin is thus now supported both by a substantial body of data in patients treated for over 2 years in clinical trials, and by experience in clinical use with a large number of patients since the drug has been available for prescription.

Natural statin like lovastatin which is mainly produced by Aspergillus terreus strains is an inhibitor of HMG-CoA reductase, an enzyme involved in the biosynthetic pathway of cholesterol. The mechanism involved in controlling plasma cholesterol levels is the reversible competitive inhibition of HMG-CoA which binds to the HMG-CoA reductase due to the structural homology between the β-hydroxyacid form of the statins and the HMG-CoA intermediate formed. Mainly Lovastatin are produced industrially by liquid submerged fermentation which decreases the production cost compared to costs of chemical synthesis. Lovastatin application part is in various field like management of hypercholesterolaemia, cholesterol lowering actions, reduce the prevalence of Alzheimer’s and renal disease etc. This review deals with the structure, properties, biosynthetic pathway, submerged fermentation, applications and side effects of lovastatin.