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An Artificial Cofactor Catalyzing the Baylis‐Hillman Reaction with Designed Streptavidin as Protein Host **
Author(s) -
Lechner Horst,
Emann Vincent R.,
Breuning M.,
Höcker Birte
Publication year - 2021
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202000880
Subject(s) - cofactor , streptavidin , chemistry , catalysis , protein engineering , host (biology) , amino acid , combinatorial chemistry , stereochemistry , biotin , organic chemistry , enzyme , biochemistry , biology , ecology
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.