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Industrial Biotransformations

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Oxygenase<br />

Nocardia autotropica<br />

● With a final product concentration of 0.8 g · L –1 and a 19,000 L reactor 15.2 kg of 6-β-hydroxymethyl-simvastatin<br />

can be produced.<br />

● The substrate is fed at an overpressure of 20 psig through an on-line filter sterilization system<br />

(microporous stainless steel prefilter, 1–2 µm, Pall) with a concentration of 20 g · L –1 . The feed<br />

tank is maintained at 45 °C to prevent precipitation.<br />

3) Flow scheme<br />

4) Process parameters<br />

yield: 24 %<br />

selectivity: 70 %<br />

reactor type: fed batch<br />

reactor volume: 19,000 L<br />

company: Merck Sharp & Dohme, USA<br />

5) Product application<br />

● Simvastatin (and derivatives) belong to the family of HMG-CoA reductase inhibitors, which<br />

are, like lovastatin, potent cholesterol-lowering therapeutic agents.<br />

6) Literature<br />

analytics<br />

E<br />

EC 1.14.14.1<br />

● Gbewonyo, K., Buckland, B.C., Lilly, M.D. (1991) Development of a large-scale continuous substrate<br />

feed process for the biotransformation of simvastatin by Nocardia sp., Biotech. Bioeng.<br />

37, 1101–1107<br />

244<br />

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cells<br />

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