Enzyme cascades for organic synthesis

The combination of sequential biocatalytic reactions in non-natural synthetic cascades is a rapidly developing field andleads to the generation of complex valuable chemicals from simple precursors [1]. By using biocatalysis underphysiological conditions in water, many parameters that are considered as green and sustainable chemistry are met.As the toolbox of available biocatalysts continues to expand, so do the options for biocatalytic retrosynthesis of atarget molecule, leading to new routes employing enzymatic transformations. To facilitate the design stage, we haveestablished RetroBioCat, a computer-aided synthesis planning tool for biocatalytic reactions and cascades [2]. Theimplementation of such cascade reactions requires careful consideration, particularly with respect to whether thepathway is constructed in vitro or in vivo, in batch format or in flow [3]. This lecture will showcase several successfulde novo cascades and discuss the relative merits of in vitro, in vivo or hybrid approaches to building biocatalyticcascades [4]. These cascades incorporate alcohol oxidations [5,6,10], C-H- activations [7] and acylations via acyl-phosphates [8] and thioesters [9].References:1.- Bell, E. L. et al. (2021) Nature Review Methods Primers 1, 46.2.- Finnigan, W. et al. (2021) Nature Catalysis 4, 98; (2023) ACS Catalysis 13 (17). 11771.3.- Mattey, A. P. et al. (2021) Angew. Chem. Int. Ed. 60, 18660.4.- France, S. P. et al. (2017) ACS Catalysis 7, 710.5.- Ford, G. J. et al. (2022) JACS Au 2, 2251.6.- Swanson, C. R. B. et al. (2023) ACS Central Science 9, 103.7.- Manning, J. et al. (2019) Angew. Chem. Int. Ed. 58, 5668.8.- Lubberink, M. et al. (2022) Angew. Chem. Int. Ed. 61, e202205054; (2023) Green Chemistry 25 (8) 2958.9.- Schnepel, C. et al. (2023) Nature Catalysis 6, 89.10.-Angelastro, A. et al. (2023) Nature Synthesis 3, 976.