Synthetic Enzymes for Synthetic Biology
Thursday, May 1, 2014: 10:35 AM
Grand Ballroom F-G, lobby level (Hilton Clearwater Beach)
Kyle Medley1, Rudesh Toofanny2, Michal Galdzicki2, Yih-En A. Ban2, Herbert Sauro1 and Alexandre Zanghellini2, (1)Bioengineering, University of Washington, Seattle, WA, (2)Arzeda Corporation, Seattle, WA
Our ability to design cell factories to produce the fuels, chemicals and drugs our industrial world needs requires the “recombination” not only of existing but also designer enzymes into novel pathways that have to be designed in a systematic and efficient manner.

In the first part of our talk we will review Arzeda’s successes in the computational de novodesign of synthetic enzymes with entirely new catalytic sites. The practical impact of our technology will be highlighted through case studies of our recent industrial collaborations, including the repurposing of existing natural active sites to catalyze novel reactions and the design of novel enzymes for the fermentation of key chemical building blocks.

In the second part of our talk, we will discuss a novel tool that Arzeda has been developing under an NSF award for the automated design of novel biosynthetic pathways. Inspired by retrosynthetic methods in organic chemistry, our software draws on databases of known natural enzymatic reactions as well as reactions that can be catalyzed by computationally designed enzymes to enumerate biosynthetic routes from a set of desired metabolites down to any small molecule of interest. Pathways are ranked based on thermodynamic feasibility, designability of each enzymatic step (with specific metrics relating to our computational enzyme design software) and overall complexity and predicted yield of the synthetic route.