Abstract
In vitro enzyme cascades possess great benefits, such as their synthetic capabilities for complex molecules, no need for intermediate isolation, and the shift of unfavorable equilibria towards the products. Their performance, however, can be impaired by, for example, destabilizing or inhibitory interactions between the cascade components or incongruous reaction conditions. The optimization of such systems is therefore often inevitable but not an easy task. Many parameters such as the design of the synthesis route, the choice of enzymes, reaction conditions, or process design can alter the performance of an in vitro enzymatic cascade. Many strategies to tackle this complex task exist, ranging from experimental to in silico approaches and combinations of both. This review collates examples of various optimization strategies and their success. The feasibility of optimization goals, the influence of certain parameters and the usage of algorithm-based optimizations are discussed.
Highlights
In vitro biocatalysis has emerged as a valuable alternative to classical chemical synthesis approaches, especially for products with complex stereochemistries such as building blocks for active pharmaceutical ingredients (APIs) [1,2]
Ongoing research provides a large number of well-characterized enzymes that catalyze reactions ranging from asymmetric ketone reduction and reductive aminations to the complex synthesis of divers natural compounds, some of which are extremely challenging to achieve with classical chemical syntheses [7,8]
Within the field of biocatalysis, the combination of two or more catalytic steps has emerged as its own field within the biocatalysis community since the 1990s, as represented by the increasing publication numbers referring to enzyme cascades or multi-step enzymatic reactions
Summary
In vitro biocatalysis has emerged as a valuable alternative to classical chemical synthesis approaches, especially for products with complex stereochemistries such as building blocks for active pharmaceutical ingredients (APIs) [1,2]. This review aims to give an overview on the provides many approaches ranging from experimental-based optimizations [19,20,21] to concepts for optimizing enzyme cascade reactions, and covers both experimental as well as in in silico approaches [22,23]. Special focus the aims to give anofoverview on the concepts for optimizing enzyme interplay initial situation, 1optimization goals and parameters to becascade adjusted.reactions, The reviewand covers both experimental as well cascade as in silico approaches. It discusses theIt different optimization includes mainly in vitro enzyme reactions with isolated biocatalysts. Working with in vitro enzyme cascades and trying to optimize them is associated in
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