PRODUCTION OF LOVASTATIN FROM FUNGAL SOURCES AND ITS MEDICAL APPLICATIONS
Hannana Maryam, Sana Maqsood, Zuriat Jabbar and Sikandar Ali*
Lovastatin and other natural as well as synthetic statins are considered as wonder drugs for treatment of hypercholesterolemia. Statins are produced by many fungal sources mainly from Aspergillus terreus on industrial scale. Lovastatin lowers blood cholesterol levels dramatically by inhibition of hydroxymethyl glutaryl-coenzyme A (HMG-CoA) reductase which is enzyme required for catalyzing rate limiting step for de novo cholesterol synthesis. This competitive inhibition is due to structural similarity between HMG-CoA and acid form of lovastatin. Lovastatin possess a hydroxyl hexahydro naphthalene ring which is polyketide chain to which different side chains are attached. Lovastatin synthesis starts from linkage of acetate units in head to tail fashion establishing main polyketide chain. First intermediate formed during synthesis is monacolin L which is then turned into monacolin J by hydroxylation which in turn gets converted into lovastatin. Molecular studies revealed that genetic cluster involved in biosynthetic pathway includes genes LovB, LovC,LovA,LovD,LovF and Lov H. Industrially lovastatin is produced by liquid submerged fermentation but now a day’s use of solid state fermentation is gaining importance. Lovastatin serves as drug of choice for cardiovascular diseases like peripheral vascular disease, atherosclerotic plaque, peripheral arterial disease, cerebro vascular disease, sepsis and ischemic heart disease. It also shows many other biological effects beyond just lowering cholesterol level that include its effects on bone maturation, renal disorders treatment, anticancer and metabolic syndrome.
Keywords: Lovastatin, hydroxymethyl glutaryl-coenzyme A, Aspergillus terreus,submerged fermentation, solid state fermentation.
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