Design and evolution of chimeric streptavidin for protein-enabled dual gold catalysis

Christoffel, Fadri and Igareta, Nico and Pellizzoni, Michela M. and Tiessler-Sala, Laura and Lozhkin, Boris and Spiess, Daniel C. and Lledos, Agusti and Marechal, Jean-Didier and Peterson, Ryan L. and Ward, Thomas R.. (2021) Design and evolution of chimeric streptavidin for protein-enabled dual gold catalysis. Nature Catalysis , 4 (8). pp. 643-653.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/84516/

Downloads: Statistics Overview


Artificial metalloenzymes result from anchoring an organometallic catalyst within an evolvable protein scaffold. Thanks to its dimer of dimers quaternary structure, streptavidin allows the precise positioning of two metal cofactors to activate a single substrate, thus expanding the reaction scope accessible to artificial metalloenzymes. To validate this concept, we report herein on our efforts to engineer and evolve an artificial hydroaminase based on dual gold activation of alkynes. Guided by modelling, we designed a chimeric streptavidin equipped with a hydrophobic lid shielding its active site, which enforces the advantageous positioning of two synergistic biotinylated gold cofactors. Three rounds of directed evolution using Escherichia coli cell-free extracts led to the identification of mutants favouring either the anti-Markovnikov product (an indole carboxamide with 96% regioselectivity, 51 turnover numbers), resulting from a dual gold σ,π-activation of an ethynylphenylurea substrate, or the Markovnikov product (a phenyl-dihydroquinazolinone with 99% regioselectivity, 333 turnover numbers), resulting from the π-activation of the alkyne by gold.
Faculties and Departments:05 Faculty of Science > Departement Chemie > Chemie > Bioanorganische Chemie (Ward)
UniBasel Contributors:Ward, Thomas R. R.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Springer Nature
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:05 Oct 2021 11:00
Deposited On:05 Oct 2021 09:17

Repository Staff Only: item control page