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Integrating computational methods to retrofit enzymes to synthetic pathways
Author(s) -
Brunk Elizabeth,
Neri Marilisa,
Tavernelli Ivano,
Hatzimanikatis Vassily,
Rothlisberger Ursula
Publication year - 2012
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.23334
Subject(s) - biochemical engineering , metabolic engineering , synthetic biology , computer science , renewable energy , computational model , chemistry , computational biology , enzyme , biochemistry , artificial intelligence , biology , engineering , ecology
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. Biotechnol. Bioeng. 2012; 109:572–582. © 2011 Wiley Periodicals, Inc.