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October 5, 2014

From Promise to Reality

Anyone who has earned a Ph.D. degree likely remembers the day when they were sitting in their advisor’s office listening to a pitch about how their project could change the world. If you really love science, and I consider myself one of the lucky researchers that loves science, then changing the world for one person or changing the world for the masses does not matter.

That being said, I really believed that I could unearth and understand all of the mysteries around a dehalogenating enzyme and that it was going to be the next great bioremediation catalyst. I suppose I didn’t think about or know all of the challenges that one might encounter trying to manipulate an enzyme into a viable biocatalyst. How in the world could you really use an enzyme to clean up water or soil systems, contaminated with halogenated organic compounds or any other contaminant? I would spend hours over beer and manuscripts with colleagues pondering how this imaginary world-altering process might work.

I first wondered how I could efficiently and quickly improve the activity of my enzyme. Would this enzyme be added as a liquid or as a solid? How would I improve enzyme stability? How would I improve the pH range in which this enzyme functions? As I carried out experiment after experiment, pouring over troves of data, in time I realized that my little enzyme that could couldn’t’ really be used as a viable biocatalyst in its current form. I am not even sure that I really understood how the industrial processes worked that the biocatalyst would have to compete with, both economically and in performance. You quickly realize that the Ph.D. experience is really about learning and training to become a scientist who knows how to properly formulate and test hypotheses. Along the way you get to attend some conferences, publish manuscripts (hopefully several), and just about the time you think you have it all figured out you are off to tackle the next project and unsolved mystery.

I look back at my experience as a graduate student with great respect and fondness for my advisor, my training environment, and my colleagues. While I was not able to make my enzyme into a viable biocatalyst, I always believed that the day enzymes could be manipulated or engineered easily and used competitively in industrial processes was a reality that would soon be realized. What I didn’t know was that this reality was already taking place and that my professional journey would take me on a collision course with a directed evolution/enzyme engineering company that makes all of the obstacles listed above nothing more than road blocks that can be overcome. The power of embracing directed evolution while letting go of some of the control associated with rational design allows us as scientists to search an incomprehensible amount of space. If a fitness function can be defined and if diversity can be generated and ranked, then an enzyme/biocatalyst can be generated that is industrially relevant. If you combine this technology with the right amount of talented scientists with some amazing robotics and High Throughput (HTP) capabilities then you can make improved variants at a rate that I didn’t know was possible. The magnitude to which enzymes increase the rates of reactions is on a scale that is unimaginable to most, and thus makes enzymes a very attractive approach for chemical manipulation. The limitation has always been that nature’s biocatalytic playbook often does not meet industrially process relevant standards. With directed evolution, the playbook is significantly expanded. What I was promised twelve years ago as a naïve first-year graduate student is a reality today.

– Scientist at Codexis

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