Optimization of lovastatin production by Aspergillus terreus ATCC 10020 using solid-state fermentation and its pharmacological applications

Abstract

Lovastatin is a potent hypocholesteremic drug. In this study lovastatin production from Aspergillus terreus ATCC 10020 was optimized using solid state fermentation with wheat bran. Incubation time, incubation temperature, initial moisture content, inoculum size, pH, and nitrogen source were screened for their effect on lovastatin production using a Plackett-Burman design. Among the tested parameters, pH and moisture content had significant effects (p < 0.05) on lovastatin production. These two parameters were then optimized using a central composite design and their optimum levels were found to be pH 8 and 80% initial moisture content. Several carbon sources were then tested with the optimized media and all sources resulted in similar lovastatin production yields. Maximum lovastatin production (8.67 mg/g dry weight substrate) was achieved on addition of 2% ammonium chloride as nitrogen source to the optimized media. This concentration was six fold greater than that obtained in the screening experiment. Also, the present study aimed to evaluate the effects of the produced lovastatin on obese diabetic mice. Results showed that lovastatin significantly (p < 0.05) decreased body mass, blood glucose, insulin, triglycerides, LDL-C, and thiobarbituric acid reactive substances while increasing glutathione, HDL-C, superoxide dismutase, and catalase compared to mice fed a high fat diet. • Optimization of lovastatin production by A. terreus in solid state fermentation. • Lovastatin significantly normalized levels of body mass, blood glucose, insulin. • Lovastatin significantly decreased triglycerides and LDL, increased HDL. • Lovastatin significantly increased SOD, CAT, GSH, decreased thiobarbituric acid. • Lovastatin produced by A. terreus had similar efficacy to commercial lovastatin.