Looking Back: A Short History of the Discovery of Enzymes and How They Became Powerful Chemical Tools

Abstract

Enzymatic approaches to challenges in chemical synthesis are increasingly popular and very attractive to industry given their green nature and high efficiency compared to traditional methods. In this historical review we highlight the developments across several fields that were necessary to create the modern field of biocatalysis, with enzyme engineering and directed evolution at its core. We exemplify the modular, incremental, and highly unpredictable nature of scientific discovery, driven by curiosity, and showcase the resulting examples of cutting-edge enzymatic applications in industry.

State-of-the-Art Biocatalysis

“…Despite their use in the fermentation process for millennia, enzymatic methods were first appreciated on the molecular level beginning in the early 1800s 20 when researchers began investigating yeasts for their fermentation abilities. 21 Though it was first believed that the entire microorganism itself was functioning as the catalyst, the discovery of the first enzyme mixture, called “diastase”, fundamentally changed the field by demonstrating that observed reactions were mediated by only specific parts of the organism. 22 This sparked increased interest in the then-new field of enzymology, and crucial milestones in understanding enzymes followed.…”

Directed Evolution of a Glutathione Transferase for the Development of a Biosensor for Alachlor Determination

“…Pesticides, although they are useful agricultural agents for fighting pests and can certainly increase food production, are also harmful to human health and environment [24][25][26]. Regulatory requirements have posed strict restrictions on maximum residue levels (MRL) that must be met before food products can enter a market [27][28][29]. As a consequence, there is a need for a robust analytical methods suitable for pesticides determination with high accuracy in food and environmental samples.…”

“…In vitro directed evolution is regarded as the most efficient method for expanding sequence diversity and creating enzymes with improved or novel properties [29,30]. Increasingly, directed evolution has been applied to create enzymes catalyzing reactions either in a more efficient way or reactions that have not been observed in nature by taking advance of the promiscuous nature of enzymes [30].…”

Flow biocatalysis 101: design, development and applications

“…Our group recently published an almost unique review on the history of enzymes and their affirmation as powerful synthetic tools. 7 The use of whole cells, also referred as fermentations, present the major drawback of possible cross-reactivity with other metabolites and naturally expressed enzymes. In addition, cellwall permeability may affect the substrate diffusion hampering its transformation, while its stability may lead to cell-lysis and loss of compartimentalization.…”