Evolving Enzymes to Create Unnatural Compounds with Tina Boville

Commodity molecules are vital ingredients for everything important to our modern world including food, energy, and medicine. However, creating these molecules still largely relies on old processes that suffer from low yield, laborious methods, and unsustainable inputs and byproducts. Tina envisions a world where all molecules are created quickly, easily, and sustainably through enzymes, biology’s chemical catalyst. Here, Tina describes how she used an extremely powerful method called directed evolution to build a novel enzyme that can create the non-canonical amino acid 4-cyanotryptophan, a fluorescent molecule that is extremely difficult to make with traditional chemistry. 

About the Author

Tina performed this work as a postdoc in the lab of Nobel Laureate Professor Frances Arnold at Caltech. The lab is world renowned for developing the methods around directed evolution and applying them to create proteins that do unnatural chemistries.Tina is now the co-founder and CEO at Aralez Bio whose focus is on developing efficient, sustainable alternatives to chemical manufacturing through enzyme engineering.

Key Takeaways

Enzymes are proteins that induce specific chemical reactions to occur. They can create molecules much more efficiently and sustainably than using traditional chemistryOne class of molecules, called non-canonical amino acids, are extremely important precursors to drugs and have specific properties that make them desirable for biotech.Making highly pure non-canonical amino acids is difficult with traditional chemistry, requiring many time-consuming reactions and toxic byproducts. But nature has yet to generate an enzyme that can create these.A process called directed evolution mimics nature’s process by heavily mutating a starting enzyme and sequentially pushing it to make a molecule of interest.When using directed evolution, “you get what you screen for”. Said another way: the outcome of the process is highly dependent on how the experiment was run and what was optimized for.With directed evolution, the non-canonical amino acid 4-cyanotryptophan is generated overnight with no harmful byproducts; something that would take a team of chemists months to do.

Translation

The evolved enzyme that creates 4-cyanotryptophan became the cornerstone technology of Aralez Bio.Tina spent the last parts of her postdoc defining customers and building a team to launch the company.Through enzyme engineering, Aralez Bio plans to replace many unsustainable and time consuming chemistries that currently plague commodity molecules.

First Author: Christina Boville

Paper: Improved Synthesis of 4-Cyanotryptophan and Other Tryptophan Analogues in Aqueous Solvent Using Variants of TrpB from Thermotoga maritima. Journal of Organic Chemistry, 2018.

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