Repozytorium

Artificial transfer hydrogenases based on the biotin- (strept)avidin technology: fine tuning the selectivity by saturation mutagenesis of the host protein.

Autorzy

C. Letondor

A. Pordea

N. Humbert

A. Ivanova

Sylwester Mazurek

M. Novic

T. R. Ward

Rok wydania

2006

Czasopismo

Journal of the American Chemical Society

Numer woluminu

128

Strony

8320-8328

DOI

10.1021/ja061580o

Kolekcja

Naukowa

Język

Angielski

Typ publikacji

Artykuł

Streszczenie

Incorporation of biotinylated racemic three-legged d6-piano stool complexes in streptavidin yields enantioselective transfer hydrogenation artificial metalloenzymes for the reduction of ketones. Having identified the most promising organometallic catalyst precursors in the presence of wild-type streptavidin, fine-tuning of the selectivity is achieved by saturation mutagenesis at position S112. This choice for the genetic optimization site is suggested by docking studies which reveal that this position lies closest to the biotinylated metal upon incorporation into streptavidin. For aromatic ketones, the reaction proceeds smoothly to afford the corresponding enantioenriched alcohols in up to 97% ee (R) or 70% (S). On the basis of these results, we suggest that the enantioselection is mostly dictated by CH/π interactions between the substrate and the η6-bound arene. However, these enantiodiscriminating interactions can be outweighed in the presence of cationic residues at position S112 to afford the opposite enantiomers of the product.

Adres publiczny

https://doi.org/10.1021/ja061580o

Strona internetowa wydawcy

https://www.acs.org/content/acs/en.html