(410b) Co-Immobilization of Enzyme Cascades Enables One-Pot Industrial Immobilized Biocatalysis | AIChE

(410b) Co-Immobilization of Enzyme Cascades Enables One-Pot Industrial Immobilized Biocatalysis


Forstater, J. H. - Presenter, Merck & Co. Inc.
Bade, R., Merck & Co., Inc.
Grosser, S. T., Merck & Co. Inc.
An, C., Merck & Co., Inc.
Kolev, J. N., Merck & Co., Inc.
Robaire, S. A., Merck & Co., Inc.
Enzymes are increasingly used to access novel chemical spaces and enable regio- and stereo-selective synthetic routes for a variety of drug substances. In many instances, biocatalytic transformations require concurrent operation of multiple enzymes to perform co-factor recycling or to enable cascaded transformations. While such transformations enable novel chemistry, they also increase the protein burden, which must be managed to both enable product isolation and mitigate potential off-target interactions from host-cell proteins which accompany unpurified recombinantly expressed proteins.

Immobilizing an enzyme to a porous resin solves many of these issues by creating a solid-supported catalyst with extremely high enzyme loads that can be prepared in advance, easily charged into a reactor, and rapidly isolated from product by filtration. We have developed a scalable enzyme-immobilization platform technology to selectively co-immobilize enzyme cascades onto a single resin directly from crude cell lysate and reject host-cell proteins. We have successfully utilized this technology to enable numerous multi-enzyme chemistries and applied it across multiple scales. In this talk we will discuss development and scale-up of multi-enzyme immobilized processes and the unique opportunities they afford for industrial immobilized biocatalysis.