With advances in biotechnology and molecular biology, we can design and engineer enzymes by modifying their underlying amino acid sequence. Doing so can confer enzymes with novel functions, which have applications in food, medicine and industrial biotechnology. Using computational protein design, PhD student Rojo Rakotoharisoa is on a quest to understand just how these proteins work and to develop strategies enabling the design of novel, highly active enzymes.
Despite successful attempts at designing artificial enzymes with substantial catalytic activity, their catalytic efficiency is still very low compared to natural enzymes. A challenge in current enzyme design methodologies lies in their limited ability to predict the correct orientation of key residues to allow efficient catalysis. To address this limitation, Rojo used an ensemble of protein scaffolds to sample favorable conformations for enzyme catalysis. Using this method, she successfully predicted the correct orientation of key residues of the designed enzyme, and recently demonstrated that this approach could be used to create novel artificial enzymes that are over 100-fold more active than previous examples. This approach is unique since previous artificial enzymes were designed using a single protein structure, which leads to artefacts and low prediction accuracy. Her approach paves the way to the design of highly efficient biocatalysts.
Enzymes work under mild conditions, which potentially lowers the cost of using them. Rojo believes that being able to design enzymes for any desired reaction is not only beneficial for industrial purposes but also for the environment, as they are less polluting than their chemical counterparts. She is confident that the design of highly efficient enzymes will broaden the knowledge of proteins and their functions within the scientific community. In the near future, we will be able to edit and design enzymes for a range of specific functions – from treating chronic diseases like phenylketonuria, to creating energy-efficient laundry detergents and even capturing greenhouse gases. Rojo attributes her success to her supervisor, Professor Roberto Chica, who guided her throughout the project.
Rojo enjoys working and interacting with people. She is particularly interested in organizing events that can positively impact the scientific community, such as an online workshop on Equity, Diversity and Inclusion (EDI) that she co-organized for fellow graduate students to inform them about EDI challenges in science. She also serves as the communications officer for PROTEO, the Quebec Network for Research on Protein Function, Engineering, and Applications, which encompasses 48 research teams from 12 institutions working on all aspects of proteins.
