Skip to main content
eScholarship
Open Access Publications from the University of California

Synthesis, Characterization, and Stoichiometric and Catalytic Reactivity of Metalloproteins Binding Noble Metals in Place of Native Metals

  • Author(s): Key, Hanna Martel
  • Advisor(s): Hartwig, John F
  • et al.
No data is associated with this publication.
Abstract

Catalysis by enzymes and transition metal complexes enables the modern synthetic

strategies used to prepare bulk and fine chemicals. However, despite their exquisite selectivity and potential for evolution, metalloenzymes are rarely used in synthetic chemistry, in part due to the limited scope of reactions catalyzed by natural metalloenzymes. To expand the scope of substrates and the range of transformations with which metalloenzymes react, two distinct approaches have been followed. One approach designs promiscuous enzymes by directed evolution. An advantage of this method is that it exploits native, selective substrate binding sites. An alternative strategy creates artificial enzymes by affixing an abiological transition metal complex within a protein scaffold by cysteine bioconjugation or biotin-labeling. Although this method has been used successfully to impart abiological activity onto enzymes, a significant drawback is that the native binding pocket of the protein scaffold is occupied by the bulky metal complex that is introduced, excluding the substrate from its natural binding site.

At the intersection of these two approaches lies a third strategy that is rarely followed: the

simple substitution of the native metal of a natural enzyme with an abiological metal. This strategy has the potential to create enzymes containing any metal of interest, while retaining the natural, evolvable substrate-binding site of the protein scaffold. We have sought new and superior approaches to the preparation, characterization, and application of diverse catalysts of this class, formed from both proteins that bind metals using organic cofactors and proteins that bind metals directly using amino acid side chains.

Despite challenges confronting their preparation, characterization, and application, our studies have revealed that diverse members of this class of artificial metalloenzymes can indeed be prepared efficiently and characterized as comprehensively as one would characterize natural enzymes and small molecule metal complexes. Moreover, the stoichiometric and catalytic reactivity of the noble metal sites within these proteins can be controlled by mutagenesis of the native substrate-binding site surrounding the abiological metal. With these studies as a foundation, we and others can now seek the creation of nearly limitless combinations of noble metals and protein scaffolds that can catalyze reactions with activities and selectivities not possible for either enzyme or transition metal catalysts alone.

Main Content

This item is under embargo until April 2, 2021.