Recombinant Yeast and Bacteria that Express Human P450s Bioreactors for Drug Discovery Development and Biotechnology 233

Steven P. Hanlon, Thomas Friedberg, C. Roland Wolf, Oreste Ghisalba, and Matthias Kittelmann

10.1 Background 234

10.1.1 Importance of Recombinant P450s for Drug Development 234

10.1.2 Fundamentals of Heterologous Expression in Bacteria 235

10.1.3 Fundamentals of Heterologous Expression in Yeast 236

10.2 Comparison of P450 Levels and Enzymic Activities in Various Models 237

10.3 Use of E. coli P450 Expression Systems in Bioreactors 240

10.3.1 General Considerations 240

10.3.2 The Roche Experience 240

10.3.2.1 Background and Utility of P450 Systems in Pharma Research 240

10.3.2.2 Fermentation of Recombinant E. coli 241

10.3.2.3 Biotransformations Catalyzed by Recombinant CYP450 241

10.3.2.4 Preparation ofN-Desethyl Amodiaquine 242

10.3.3 The Novartis Experience 244

10.3.3.1 Introduction 244

10.3.3.2 Production of E. coli Cells with CYP Activity 244

10.3.3.3 Whole Cell Biotransformation 246

10.3.3.4 Recent Developments 246

10.4 Conclusion 246 References 247

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