Cytochrome P450 (CYP) bioreactors play a major role in establishing the practical use of this enzyme family in
academia and industry. The current demand for enzymatic hydroxylations of unactivated carbons in the parmaceutical industry
includes the preparation of drug metabolites and various hydroxylated synthetic precursors as well as the enzyme
mediated lead diversification and natural product synthesis, most of which require multigram scale synthesis. To date, the
large scale application of CYPs in the synthesis of oxygenated compounds is limited by many challenges. This review describes
relevant examples of CYP oxidations and also presents the strategies available to overcome such challenges. At
present, P450 catalyzed reactions can only be performed at substrate concentrations ranging from 1-25 mM, unlike other
biocatalytic redox reactions like ketone reductases, typically performed at substrate loads greater than 500 mM. The
emergence of powerful expression methods and a large number of CYP mutants developed for specific applications holds
the promise for future industrial applications. The search for higher volumetric productivities is however a task that needs
to be addressed not only through the use of protein engineering as the primary tool but significant emphasis needs to be
placed on process development through exploring multiple operating schemes, optimizing reaction media and modifying
microbial strains needed for heterologous expression.
Keywords: Bioreactor, CYP, challenges, oxidation, preparation, pharmaceutical, scale up.
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