A Vision of my Career: Finding the Alchemist Stone for the 21st Century

My favorite alchemist Hennig Brand by Joseph Wright.

These are exciting times for me as I gear up for recruiting weekend Rice and meditate on UT's recruiting event. I am preparing for the upcoming interviews with some of my favorite Professors by reading their papers and figuring out who I am and what I want to do. Today I will share with the entire world (or just those that reads this blog) why I do science and what I hope to accomplish in my career as a researcher.

Once, I dreamed of molecular dynamic simulations and being able to engineering enzymes to order. As I survey the field of protein engineering, I feel that we are in a much better place as far as making enzymes to order than when I first started following it in 2004. Now I feel that the struggle is to take the next step and build pathways to order. Perhaps I am overestimating the power of directed evolution, but I am confident that its only going to get easier.

My current vision of the work that I want to develop over the course of my career is the use of microbes (bacteria and yeasts) as chemical factories. Now we can use molecular cloning tools to copy & paste whatever enzymatic pathways we want into them, requiring only sugar for their augmented metabolism. I can't help but draw a parallel with the famed Alchemist Stone, which was reputed to turn lead into gold. This "alchemist stone of the 21st Century" will be the methodology combining protein and metabolic engineering. Believe it.

In stepwise manner we turn lead (sugar or cheaper carbon sources) into precious gold (i.e. expensive pharmaceuticals and specialty chemicals):

1) We select a production chassis. This will probably be bacteria (E. coli) or yeast (S. cerevisiae).

2) We clone out the production pathway from libraries or other organisms into our chassis.
a) If no enzymes exist for that chemical reaction, protein engineering provides a toolkit such as directed evolution to evolve it from similar enzymes.
b) Computational simulation provides an alternative to directed evolution by making educated guesses about mutations which may produce that activity.

3) Next the pathway must be optimized in the microbe for maximum flux. Techniques for this involve modeling the pathway based on production in intermediates and up-regulating the steps acting as a bottleneck. This can be done one enzyme at a time or using directed evolution.

4) Now that the pathway is in the microbe and producing the most of our "gold" possible we can opt to switch its "lead" to something else which is cheaper (plant biomass, recycled plastic, or even urban refuse) in similar manner as putting the production pathway in.

5) Last we can include a production "switch", in the form of an inducible promoter, that we can turn on to push the microbes to the limit before we spin it all down and collect our hard earned prize.

These microbes can be freezed down, dried out and otherwise sent anywhere for production of your product. Thus technology transfer within a company or between countries is easily facilitated. The final purification may be tricky to get setup at a biochemical plant, but growing microbes is easy and straightforward.