Enabling protein-hosted organocatalytic transformations.

Alexander R Nödling,Nicolò Santi,Thomas L Williams,Louis Y P Luk,Yu-Hsuan Tsai

doi:10.1039/d0ra01526a

Alexander R Nödling, Nicolò Santi + Show 3 more

Open Access

https://doi.org/10.1039/d0ra01526a

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Abstract

In this review, the development of organocatalytic artificial enzymes will be discussed. This area of protein engineering research has underlying importance, as it enhances the biocompatibility of organocatalysis for applications in chemical and synthetic biology research whilst expanding the catalytic repertoire of enzymes. The approaches towards the preparation of organocatalytic artificial enzymes, techniques used to improve their performance (selectivity and reactivity) as well as examples of their applications are presented. Challenges and opportunities are also discussed.

Highlights

Biocompatible organocatalysisServing as a major tool for asymmetric chemical transformations,[1,2,3] organocatalysis has matured to a point where its bio-orthogonality can be exploited for important chemical and synthetic biology applications
The development of organocatalytic artificial enzymes will be discussed. This area of protein engineering research has underlying importance, as it enhances the biocompatibility of organocatalysis for applications in chemical and synthetic biology research whilst expanding the catalytic repertoire of enzymes
Provided its bio-orthogonality, organocatalysis can be used in biological contexts for valuable chemical and biological applications.[10,11,12,13,14,15,16,17]

Summary

Introduction

Biocompatible organocatalysisServing as a major tool for asymmetric chemical transformations,[1,2,3] organocatalysis has matured to a point where its bio-orthogonality can be exploited for important chemical and synthetic biology applications. It was found that unnatural amino acid replacement at the Val[15] position yielded the most promising result (Fig. 10b).[75] Laboratory evolution was used to screen the library variants in 96 well plates by measuring the loss of the UV absorbance from the substrate.[50] The resulting variant which carries additional mutations, including A11L, N19M, A92R and F93H, showed a 74-fold increase in catalytic efficiency.

Results

Conclusion