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Integrated Computational and
Experimental Approaches to Facilitated Model Development—Genomatica, Inc.,
5405 Morehouse Drive, Suite 210, San Diego, CA
92121; 858-362-8550, www.genomatica.com
Dr. Radhakrishnan Mahadevan,
Dr.
DOE Grant No. DE-FG02-05ER84280
Amount: $99,508
Advances in biotechnology have lead to the sequencing of several microbial genomes with important applications in bioremediation, CO2 sequestration, and alternative energy sources. Genome-scale, constraint-based modeling has been shown to be successful in unraveling the genotype-phenotype relationship and for predicting physiology under varied conditions. However, the development of such genome-scale models is labor intensive and time consuming. This project will develop methods for the facilitated development of genome-scale models based on the genome sequence and high-throughput phenotyping. The models will enable the rational design of strategies for improving the efficiency of bioremediation, CO2 sequestration, and other processes related to the DOE’s core missions. Phase I will develop approaches for automated metabolic reconstruction, based on both the genome sequence and comparison with existing high quality metabolic models. Methods also will be developed to automatically identify candidate reaction sets to close gaps in the metabolic pathways associated with the synthesis of essential biomass components. The approach will be validated by developing an metabolic model of Pseudomonas fluorescens and Bacillus subtilis.
Commercial Applications and Other Benefits as described by the awardee: The technology should lead to the rapid development of cellular models, enabling the application of the model-drive research for efficient biological discovery to all the sequenced microorganisms. The reduced timeline of the model development process also should facilitate the development of cellular in silico models for several strains of industrially relevant microorganisms.