Abstract
Statins series were often prescribed as a therapeutic medicine for controlling hypercholesterolemia. Lovastatin, also called monacolin K and mevinolin, is one of the statins series. Lovastatin can be hydrolyzed by an enzyme named lovastatin esterase to cleave its side chain to form monacolin J, also called triol acid, which is the core structure of various statins for synthesis of other statins. Using Clonostachys compactiuscula, we were able to demonstrate the conversion of lovastatin to form monacolin J. Response surface methodology was used to achieve the optimization of the conversion process. To study the proposed second-order polynomial model, we used a central composite experimental design with multiple linear regression to estimate the model coefficients of the five selected factors believed to influence the conversion process. The experimental results indicated that the optimal conditions for complete conversion of lovastatin to form monacolin J by using C. compactiuscula mycelium lysate were obtained as follows: glucose content of the medium 0.59%, the initial pH of the medium 8.5, mycelium incubation time 4 days, and the conversion time 15 hours. Under such a condition, the optimal concentration of substrate lovastatin was 1 mg/ml. The lovastatin esterase was isolated and purified from the mycelium of C. compactiuscula by a series of ammonium sulfate precipitation, size-exclusion chromatography, and ion-exchange chromatography. The partially purified enzyme showed a homopolymer peptide with a molecular mass of 28-kDa found by SDS-PAGE. The converted product, monacolin J, was isolated and purified, and its structure was verified by NMR.