Continuous bioprocessing (“Enz-Flow”) is a new and highly relevant paradigm for organic chemists to consider. Bioprocessing offers highly sustainable, efficient and cost-effective molecule production by using enzymes engineered specifically to optimally catalyze these transformations. Traditionally, metal or organocatalysts have been the main source of catalytic enantioselectivity; the use of engineered enzyme bioprocessing can increase sustainablility, affordability and substrate selectivity. Combining continuous processing methodologies and biocatalytic technologies <i>via</i> immobilization strategies can further improve molecule generation while reducing the use of harsh and expensive chemicals and substantially contributing to establishing greener chemical syntheses.<br/>Recently, the engineering of enzymes to perform selective chemical synthesis has been demonstrated to rapidly expand the range of reactions that can be performed under biocatalytic conditions. This work explores an array of whole cell immobilization strategies in order to achieve continuous bioprocessing of enantioselective cyclopropanations using engineered enzymes (BM3-Hstar and Mb H64V V68A, in collaboration with the Arnold group at the California Institute of Technology). This whole cell immobilization approach eliminates the need for further purification of the engineered enzyme, facilitating rapid affordable generation of the catalyst with quick target molecule turnover. Cyclopropanation methodologies such as these can be applied towards the synthesis of a variety of active pharmaceutical ingredient (API) targets. “Enz-Flow” approaches for molecule making have the potential to enable sustainable large-scale production of APIs due to the reproducible scalability of continuous processing systems.

Continuous bioprocessing (Enz-Flow) approaches toward levomilnacipran synthesis

253rd National Meeting (2017)

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