HMG-CoA Reductase Inhibitor인 Pravastatin의 생산성 향상

Pravastatin sodium, competitive inhibitors of HMG-CoA(3-hydroxy-3-methylglutaryl coenzyme A) reductase, is produced from the culture broth of Streptomyces carbophilus KCCM 10370, The production of Pravastatin sodium was increased about 45 fold compared to wild type by UV mutation. Production of Pravastatin was also improved by continuous feeding of Compactin sodium to 24% and bioconversion ratio was also increased to 4.3% by intermittent addition. In main culture, concentration of Compactin sodium was kept less than 0.1%(w/v) under continuous feeding of Compactin sodium then product was 0.49% and bioconversion was 70%. After finishing the fermentation, Pravastatin was purified by various chromatographies such as Diaion HP20 resin column, Partition, and ODS(Octa-Decylsilyl Silicagel) resin column with a final yield of 70~72% and over 99.7% purity. The IR, UV, and NMR study of the purified Pravastatin sodium showed the same pattern as that of EP(European Pharmacopoeia).