An Artificial Cofactor Catalyzing the Baylis‐Hillman Reaction with Designed Streptavidin as Protein Host. (16th February 2021)

• Record Type: Journal Article
• Authors: Lechner, Horst; Emann, Vincent R.; Breuning, M.; Höcker, Birte
• Is Part Of: Chembiochem. Volume 22:Number 9(2021)
• Page Start: 1573
• Page End: 1577
• Publication Date: 2021-02-16
• Subjects: artificial cofactors -- Baylis-Hillman reaction -- biocatalysis -- protein design -- streptavidin; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.202000880
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: An artificial cofactor based on an organocatalyst embedded in a protein has been used to conduct the Baylis‐Hillman reaction in a buffered system. As protein host, we chose streptavidin, as it can be easily crystallized and thereby supports the design process. The protein host around the cofactor was rationally designed on the basis of high‐resolution crystal structures obtained after each variation of the amino acid sequence. Additionally, DFT‐calculated intermediates and transition states were used to rationalize the observed activity. Finally, repeated cycles of structure determination and redesign led to a system with an up to one order of magnitude increase in activity over the bare cofactor and to the most active proteinogenic catalyst for the Baylis‐Hillman reaction known today. Abstract : A story in pictures : An artificial cofactor based on an organocatalyst was embedded in streptavidin to catalyze the Baylis‐Hillman reaction. The following protein design process was described by solved crystal structures for every design step, and the outcome of the chemical reaction was represented by using DFT calculations and MD simulations.