title: Integrating computational methods to retrofit enzymes to synthetic pathways.
abstract: Microbial production of desired compounds provides an efficient framework for the development of renewable energy resources. To be competitive to traditional chemistry, one requirement is to utilize the full capacity of the microorganism to produce target compounds with high yields and turnover rates. We use integrated computational methods to generate and quantify the performance of novel biosynthetic routes that contain highly optimized catalysts. Engineering a novel reaction pathway entails addressing feasibility on multiple levels, which involves handling the complexity of large-scale biochemical networks while respecting the critical chemical phenomena at the atomistic scale. To pursue this multi-layer challenge, our strategy merges knowledge-based metabolic engineering methods with computational chemistry methods. By bridging multiple disciplines, we provide an integral computational framework that could accelerate the discovery and implementation of novel biosynthetic production routes. Using this approach, we have identified and optimized a novel biosynthetic route for the production of 3HP from pyruvate.
authors.affiliation: Laboratory of Computational Chemistry and Biochemistry, EPFL, CH-1015 Lausanne, Switzerland.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Brunk
authors.forename: Marilisa
authors.initials: M
authors.lastname: Neri
authors.forename: Ivano
authors.initials: I
authors.lastname: Tavernelli
authors.forename: Vassily
authors.initials: V
authors.lastname: Hatzimanikatis
authors.forename: Ursula
authors.initials: U
authors.lastname: Rothlisberger
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism*; D019344:Lactic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D060847:Metabolic Engineering / Q000379:methods*; D053858:Metabolic Networks and Pathways; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D019289:Pyruvic Acid / Q000737:chemistry / Q000378:metabolism; D058615:Synthetic Biology / Q000379:methods*; D013816:Thermodynamics
chemical_list: D004798:Enzymes; D019344:Lactic Acid; D019289:Pyruvic Acid; C031601:hydracrylic acid