Engineered enzymes for the synthesis of pharmaceuticals and other high-value 
products

Reetz, Manfred T.; Qu, Ge; Sun, Zhoutong

doi:10.1038/s44160-023-00417-0

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Engineered enzymes for the synthesis of pharmaceuticals and other high-value products

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Reetz, Manfred T.
Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences;
Research Department Reetz, Max-Planck-Institut für Kohlenforschung, Max Planck Society;

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引用

Reetz, M. T., Qu, G., & Sun, Z. (2024). Engineered enzymes for the synthesis of pharmaceuticals and other high-value products. Nature Synthesis, 3, 19-32. doi:10.1038/s44160-023-00417-0.

引用: https://hdl.handle.net/21.11116/0000-000E-3FA7-0

要旨

Catalysis has a central role in organic synthetic methodology, especially in stereoselective reactions. In many reactions, enantioselectivity is made possible through the use of chiral transition metal catalysts. For decades, enzymes had a minor role, but this changed with the advent of directed evolution in the 1990s. The experimental implementation of evolving stereoselective mutants convinced at least some chemists of the potential of enzymes in catalytic processes. Subsequently, efficient mutagenesis methods emerged, including the combinatorial active-site saturation test, iterative saturation mutagenesis and rational enzyme design, such as focused rational iterative site-specific mutagenesis, that led to the widely held belief that essentially any desired transformation is possible. In this Review, we introduce these mutagenesis strategies and then discuss individual cases of enzyme-catalysed syntheses of chiral therapeutic drugs and other value-added products as well as the associated reaction mechanisms. Also, the type of value-added product, the enzyme used and preferential mutagenesis method are discussed.