Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Weis, R; Winkler, M; Schittmayer, M; Kambourakis, S; Vink, M; Rozzell, JD; Glieder, A.
A Diversified Library of Bacterial and Fungal Bifunctional Cytochrome P450 Enzymes for Drug Metabolite Synthesis
ADV SYNTH CATAL. 2009; 351(13): 2140-2146.
Doi: 10.1002/adsc.200900190
Web of Science
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- Co-authors Med Uni Graz
- Schittmayer-Schantl Matthias
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- Abstract:
- Innovative biohydroxylation catalysts for the preparation of drug metabolites were developed from scratch. A set of bacterial and fungal sequences of putative and already known bifunctional P450 enzymes was identified by protein sequence alignments, expressed in Escherichia coli and characterised. Notably, a fungal self-sufficient cytochrome P450 (CYP) from Aspergillus fumigatus turned out to be especially stable during catalyst preparation and application and also in presence of organic co-solvents. To enhance the catalytic activity and broaden the substrate specificity of those variants with high expression levels prominent single mutations were introduced. Selected improved variants were then used as lyophilised bacterial lysates for the synthesis of 4'-hydroxy-diclofenac and 6-hydroxychlorzoxazone, the two metabolites of active pharmaceutical compounds diclofenac and chlorzoxazone representing the same metabolites as generated by human P450s.
- Find related publications in this database (Keywords)
- active pharmaceutical ingredients (APIs)
- cytochrome P450 (CYP)
- hydroxylation
- metabolites
- mutagenesis