In the past decade, carbene transfer biocatalysis has evolved from basic scientific research to an area with vast potential for the development of new industrial processes in the pharmaceutical industry. Despite the growing significance of these “carbene transferases”, it is surprising that their development is based on a very narrow range of proteins, mostly Cyt. P450s and myoglobin (Mb). However, in the case of Mb, it is not clear whether this protein is in fact a suitable choice, given the lack of a “real” active site, and in fact, we argue that this protein was mainly chosen for convenience and stability reasons. In this study, we show that YfeX, naturally a peroxidase, is a much superior choice as a platform for further biocatalyst development. YfeX has an incredible potential for the development of new carbene transferases, with an intrinsic reactivity of the wild-type (WT) protein that is in many cases on par with the best Mb mutants available to this date. In addition, the protein shows high stability against organic solvents, thereby enabling the use of organic co-solvents whenever necessary to solubilize substrates in order to improve turnover. Excitingly, YfeX is able to catalyze the Si—H insertion of dimethylphenylsilane with 11% yield, which is the highest yield for any WT protein observed so far. QM/MM calculations reveal further details of the mechanism of the unusual Si—H insertion reaction that is catalyzed by YfeX.

YfeX – a new platform for carbene transferase development with high intrinsic reactivity

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