Protein Engineering & Computational Protein Design

We specialize in the development of novel proteins with useful properties for their application in chemistry and biology. In particular, we are interested in developing designer biocatalysts for chemical synthesis as well as genetically-encoded biosensors based on fluorescent proteins for in vivo imaging applications. To achieve these goals, we develop and exploit multistate computational protein design methods to predict mutations leading to the desired protein property. More information on our research projects can be found in the Research section.

Latest Results

Parmeggiani F et al. (2019) ACS Catalysis 9, 3482–3486.

In this collaborative project with the group of Nicholas Turner (U. Manchester), we used rational design to engineer the first reported aminotransferase displaying native-like catalytic activity towards D-tryptophan (kcat/KM = 700 M-1 s-1). This engineered variant enabled us to develop a one-pot biocatalytic process that combines asymmetric synthesis of substituted L-tryptophans from indoles by tryptophan synthase (TrpS), with a stereoinversion cascade based on L-amino acid deaminase (LAAD) and our engineered aminotransferase (DAAT). We show that this biocatalytic process can be used for the synthesis of 12 D-tryptophan derivatives containing electron-donating or withdrawing substituents at all benzene-ring positions on the indole group, with high conversion rate (84% to >99%) and enantiomeric excess (91% to >99%) starting from commercially-available materials. We also demonstrate that our process is applicable to preparative-scale synthesis of all 12 D-tryptophans (isolated yields of 63% to 79%), many of which are highly-valuable building blocks of pharmaceuticals and natural products.

 

Previous results can be found here.

 

Research Funding

We gratefully acknowledge support from the following agencies:

 

Keywords

Protein Engineering, Computational Protein Design, Multistate Design, Enzymes, Biocatalysis, Fluorescent Proteins, Protein Dynamics, Molecular Modeling, Protein Science, High-Performance Computing, Biological Chemistry

 

Contact info

Roberto Chica, Ph. D.
Associate Professor
Department of Chemistry and Biomolecular Sciences
University of Ottawa
10 Marie Curie
Ottawa, ON K1N 6N5
Canada

(613) 562-5800 x 1988
rchica at uottawa dot ca