PURIFICATION AND CHARACTERIZATION OF A LOVASTATIN ESTERASE FROM CLONOSTACHYS COMPACTIUSCULA

An esterase from the fungus Clonostachys compactiuscula selectively hy drolyzes lovastatin, a clinically useful antihypercholesterolemic agen t. Lovastatin or lovastatin-related compounds were required to induce the activity of the lovastatin 8'-(alpha-methylbutyryloxy) esterase, T he 46-kDa esterase was purified from mycelial extracts by centrifugati on and a single anion-exchange chromatographic separation, Maximal lov astatin esterase activity was found at pH 9.0 to 9.6 and at 25 to 30 d egrees C. The addition of 5 to 20% methanol resulted in greater lovast atin hydrolysis, while the addition of other solvents (ethanol, isopro panol, butanol, ethyl acetate, isopropyl acetate, or tetrahydrofuran) decreased hydrolysis, Lovastatin was selectively hydrolyzed even in th e presence of an excess of simvastatin, another antihypercholesterolem ic agent that is structurally very similar to lovastatin, This lovasta tin 8'-(alpha-methylbutyryloxy) esterase can be used to prepare a core intermediate for the generation of novel antihypercholesterolemic age nts or to purify simvastatin prepared by C methylation of the 2(S)-met hylbutyryloxy side chain of lovastatin.