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Constructing Biocatalytic Cascades: In Vitro and in Vivo Approaches to de Novo Multi-Enzyme Pathways

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School of Chemistry, Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom
*E-mail for N.J.T.: [email protected]
*E-mail for S.L.F.: [email protected]
Cite this: ACS Catal. 2017, 7, 1, 710–724
Publication Date (Web):December 12, 2016
https://doi.org/10.1021/acscatal.6b02979
Copyright © 2016 American Chemical Society

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    Abstract

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    The combination of sequential biocatalytic reactions, via non-natural synthetic cascades, is a rapidly developing field and leads to the generation of complex valuable chemicals from simple precursors. As the toolbox of available biocatalysts continues to expand, so do the options for biocatalytic retrosynthesis of a target molecule, leading to alternative routes employing enzymatic transformations. The implementation of such cascade reactions requires careful consideration, particularly with respect to whether the pathway is constructed in vitro or in vivo. In this Perspective, we describe the relative merits of in vitro, in vivo, and hybrid approaches to building biocatalytic cascades and showcase recent developments in the area. We also highlight the factors that influence the design and implementation of purely enzymatic or chemoenzymatic, one-pot, multistep pathways.

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