Screening of A. terreus Klvb28 mutants by bioassay method for overproduction of lovastatin (a vital statin in Coronary Heart Disease)

Abstract

Coronary Heart Disease (CHD) is the main clinical manifestation of atherosclerosis and is the major cause of death in modern days. One of the major risk factors for atherosclerosis and coronary heart disease is hypercholesterolemia. Lovastatin is a potent cholesterol-lowering drug. It acts by competitively inhibiting the enzyme 3-hydroxy-3- methylglutaryl coenzyme A reductase (HMG-CoA) which catalyses the rate-limiting step of cholesterol biosynthesis. Lovastatin is produced as a secondary metabolite by a variety of filamentous fungi including Penicillium sp., Monascus rubber and Aspergillus terreus. However these organisms suffer from low yield. Hence, in the present study the strain A. terreusKLVB28 isolated from soil was subjected to mutation for over-production of lovastatin by chemical as well as physical methods. Over all 43 mutants were obtained, amongst obtained mutants A. terreus KLVB8mu21 (obtained after EMS treatment of 5mg/ml for 5min treatment) is potent lovastatin producer when employed for bioassay determination. Confirmation of lovastatin by TLC and spectral analysis at 238 nm serves as alternative method for HPLC which is an expensive method.