(172g) Invited Talk: Progress in Biocatalysis: From Computational Protein Design to Enzyme Process Engineering

Biocatalysis has seen rapid development over the last few years. Protein engineering techniques now encompass not only rational combinatorial design but increasingly computational techniques. When those computational techniques rely on increasingly large data sets, AI/ML stands to greatly impact the workflow of biocatalysis development. The presentation will outline some vignettes of successful biocatalysis development, both from the presenter’s lab as well as from the academic and industrial community.

Evolvability of biocatalysts is a central theme in research and applications. The presentation will compare some recent cases, including Merck’s islatravir and Novartis’ development of an imine reductase (IRED) with both protein engineering and computational techniques.

Biocatalysis development often operates within trade-offs, such as between different catalytic activities and between activity and stability. The latter can be resolved by optimizing process or operational stability, expressed by the Total Turnover Number (TTN), rather than trying to optimize either dimension of merit separately. The presentation will cover latest results and insights from optimization work on amino ester hydrolase (AEH), an alternative to the more common Pen G acylase (PGA).

When designing reactors around enzyme-catalyzed reactions, accurate enzyme kinetics are crucial. Reactor performance in beta-lactam antibiotics synthesis is strongly impacted by minor enzyme inhibition that had not been detected under laboratory conditions. Data analysis employing Bayesian analysis and neural ODEs enable the formulation of a more robust kinetic model with given experimental data. Again, we will present newest results and insights.