Genomes to Life Contractor-Grantee Workshop III
February 6-9, 2005, Washington, D.C.
Bioinformatics, Modeling, and Computation
62
OptStrain: A Computational Framework for Redesign Microbial Production Systems
Priti Pharkya and Costas D. Maranas* (costas@psu.edu)
Pennsylvania State University, University Park, PA
In this talk, we will discuss the hierarchical computational framework OptStrain aimed at guiding pathways modifications, through reaction additions and deletions, of microbial networks for the overproduction of targeted compounds. A comprehensive database of biotransformations, referred to as the Universal database (with over 5,700 reactions), is compiled and regularly updated by downloading and curating reactions from multiple biopathway database sources. Combinatorial optimization is then employed to elucidate the set(s) of non-native functionalities, extracted from this Universal database, to add to the examined production host for enabling the desired product formation. Subsequently, competing functionalities are identified and removed to ensure higher product yields coupled with growth. This work establishes an integrated computational framework capable of constructing stoichiometrically balanced pathways, imposing maximum product yield requirements, pinpointing the optimal substrate(s), and evaluating different microbial hosts. The range and utility of OptStrain is demonstrated by addressing a variety of product molecules and experimental verifications.
* Presenting author
