Synthetic cascades are enabled by combining biocatalysts with artificial metalloenzymes
Author: ["V. Köhler","Y. M. Wilson","M. Dürrenberger","D. Ghislieri","E. Churakova","T. Quinto","L. Knörr","D. Häussinger","F. Hollmann","N. J. Turner","T. R. Ward"]
Publication: Nature Chemistry
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Abstract
Enzymatic catalysis and homogeneous catalysis offer complementary means to address synthetic challenges, both in chemistry and in biology. Despite its attractiveness, the implementation of concurrent cascade reactions that combine an organometallic catalyst with an enzyme has proven challenging because of the mutual inactivation of both catalysts. To address this, we show that incorporation of a d6-piano stool complex within a host protein affords an artificial transfer hydrogenase (ATHase) that is fully compatible with and complementary to natural enzymes, thus enabling efficient concurrent tandem catalysis. To illustrate the generality of the approach, the ATHase was combined with various NADH-, FAD- and haem-dependent enzymes, resulting in orthogonal redox cascades. Up to three enzymes were integrated in the cascade and combined with the ATHase with a view to achieving (i) a double stereoselective amine deracemization, (ii) a horseradish peroxidase-coupled readout of the transfer hydrogenase activity towards its genetic optimization, (iii) the formation of L-pipecolic acid from L-lysine and (iv) regeneration of NADH to promote a monooxygenase-catalysed oxyfunctionalization reaction. An artificial transfer hydrogenase, based on the incorporation of a biotinylated iridium-piano-stool complex in streptavidin, is shown to be fully compatible with a range of biocatalysts. The location of the active metal centre inside the protein scaffold efficiently prevents mutual inactivation processes and enables the concurrent interplay with oxidative enzymes.
Cite this article
Köhler, V., Wilson, Y., Dürrenberger, M. et al. Synthetic cascades are enabled by combining biocatalysts with artificial metalloenzymes. Nature Chem 5, 93–99 (2013). https://doi.org/10.1038/nchem.1498