Department of Chemical Engineering
Heroon Politechniou 9,
University Campus, Zografou,
Athens 15780
ABSTRACT
Presentation Room "N. Koumoutsou"
Dr. Linda J.Rekoske-Broadbelt
Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL, U.S.A
Discovery and Analysis of Novel Biochemical Transformations
We have developed methods for the assembly of kinetic models of substantive detail to be built that enable the atomic scale to be linked with the process scale. We have applied our methodology to a wide range of different problems, including production of silicon nanoparticles, biochemical transformations, polymerization and depolymerization, and tropospheric ozone formation. While the chemistries we have studied are seemingly very disparate, applying a common methodology to study them reveals that there are many features of complex reaction networks that are ubiquitous. This presentation will focus on one of the systems we have examined: biochemical production of fuels and chemicals. It will be shown how reaction pathway analysis can be used to discover novel routes to small molecules.
The talk will focus on designing novel pathways for the sustainable microbial production of high-value organic compounds as an attractive alternative to organic syntheses that utilize petrochemical feedstocks. For example, the high cost of and the numerous applications for 3-hydroxypropanoate (3HP) make it a valuable target for biosynthesis. We applied the Biochemical Network Integrated Computational Explorer (BNICE) framework for the automated construction and evaluation of metabolic pathways to explore novel biosynthetic routes for the production of 3HP from pyruvate. Among the pathways to 3HP generated by the BNICE framework were all of the known pathways for the production of 3HP and numerous promising novel pathways. The pathways generated for the biosynthesis of 3HP were ranked based on four criteria: pathway length, thermodynamic feasibility, maximum achievable yield to 3HP from glucose during anaerobic growth, and maximum achievable intracellular activity at which 3HP can be produced. Thermodynamic feasibility was assessed using a group contribution method in combination with Thermodynamics-based Metabolic Flux Analysis (TMFA). TMFA was also utilized in all yield and maximum achievable activity calculations. Four pathways emerged from this ranking as the most promising pathways for the biosynthesis of 3HP, and three of these pathways, including the two shortest pathways discovered, were novel. We also discovered novel routes for the biosynthesis of 28 commercially available compounds that are currently produced exclusively through organic synthesis.
