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P. 54-57 /

A sustainable P450 oxygenation technology for the selective synthesis of oxygenated intermediates and APIs

corresponding

IWONA KALUZNA*, ANDRE DE VRIES,
DANIEL MINK

*Corresponding author
DSM Chemical Technology R&D BV
Urmonderbaan 22, P.O. Box 18, 6160 MD Geleen, The Netherlands

Abstract

Oxyfunctionalization of non-activated C-H bond can be accomplished by using highly versatile biocatalysts such as cytochrome P450 enzymes. The potential of P450 enzymes has not been fully exploited since there are some limiting factors in the wider implementation of these catalysts for commercial purposes. Currently DSM focuses on the development of a P450 oxygenase platform technology by addressing current limitations of these enzymes in terms of activity, substrate scope, and performance under industrially relevant conditions. 
By designing combinatorial libraries DSM developed a large collection of P450 enzymes with broad and diverse substrate specificity. Substrate profiling of this P450 platform was achieved by parallel multi-component screening using state-of-the-art LC/MS and flow NMR analysis. Exemplarily one P450 reaction from this screening was scaled up to a Kg scale. Application of the P450 technology for intermediate synthesis resulted in product concentration of 10 g/L and a space – time yield of 1.5 g/L/h.


INTRODUCTION

Increasing demand for oxygenated molecules with application as food and feed, flavours and fragrances, cosmetics and materials revealed an unmet need for cost effective and sustainable routes towards aforementioned targets. One of the widely acknowledged approaches to oxyfunctionalization of C-H bond is application of highly versatile catalysts such as cytochrome P450 enzymes (CYPs or P450s). Cytochrome P450 enzymes are multipurpose biocatalysts that introduce oxygen into a vast range of molecules. The extraordinary ability of these enzymes to catalyze a diverse variety of oxygenation reactions in a regio- and stereoselective mode under mild conditions make them highly desirable catalysts for drug development, bioremediation and in the synthesis of