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. 2024 Nov 19;60(93):13746-13749.
doi: 10.1039/d4cc05182c.

Installation of an organocatalyst into a protein scaffold creates an artificial Stetterase

Alice MacAulay  1 , Eva Klemencic  1 , Richard C Brewster  1 , Süleyman Mert Ünal  2 , Evangelia Notari  1   2 , Christopher W Wood  2 , Amanda G Jarvis  1 , Dominic J Campopiano  1
Affiliations

Installation of an organocatalyst into a protein scaffold creates an artificial Stetterase

Alice MacAulay et al. Chem Commun (Camb). .

Abstract

Using a protein scaffold covalently functionalised with a thiamine-inspired N-heterocyclic carbene (NHC), we created an artificial Stetterase (ArtiSt) which catalyses a stereoselective, intramolecular Stetter reaction. We demonstrate that ArtiSt functions under ambient conditions with low catalyst loading. Furthermore, activity can be increased >20 fold by altering the protein scaffold.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. (A) The chemical structure of the enzyme cofactor thiamine pyrophosphate (TPP) showing the C2-proton (red), pyrophosphate (PPi, blue) and pyrimidine (PYR, green). (B) The structure of a chiral triazolium salt used by Rovis in 2009 to catalyse an intramolecular Stetter reaction. (C) The structure of N-benzyl-4-bromomethylthiazolium bromide prepared by Suckling in 1993 to modify papain for use in an intramolecular benzoin condensation. (D) A scheme of this work showing the structure of the thiazolium salt (MBnThz, 1) and its functionalisation of a cysteine-containing protein scaffold to create the artificial Stetterase (ArtiSt).
Scheme 1
Scheme 1. The intramolecular Stetter reaction catalysed by different thiazolium functionalised SCP scaffolds (ArtiSt).
See this image and copyright information in PMC

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