Title: ``Integrating (x)omics Technologies with Protease Production in Bacillus subtilis''
Speaker: Dr. Jeff Varner; Metabolic Pathway Engineering, Genencor International Inc. Palo Alto, CA
Place: Stanley Coulter (SC) 239; Tuesday, 4:30pm


An industrial case study of the application of (x)omics technologies to process improvement is presented. A mathematical model of minimal media fed-batch protease production in Bacillus subtilis is developed using genome-wide transcriptional information and on/off-line physiological measurements. The model, composed of > 700 reactions compiled from literature, BSubCyc and KEGG, describes central carbon metabolism, amino acid biosynthesis, oxidative phosphorylation and the biosynthesis of cellmass macromolecules.

Affymetrix GeneChip arrays are used to sample the transcriptional state of Bacillus subtilis every two hours over the course of 14L fed-batch production runs. The resulting transcriptional datasets are mined using dynamic modeling techniques to produce a putative transcriptional regulatory network. The putative network, along with 13C-NMR flux ratios, is integrated with Flux Balance Analysis (FBA) to estimate carbon and energy flow through central metabolism.

Model estimated transcriptional and metabolic state is compared with experiment for different feeding regimes. It will be shown that key physiological shifts estimated by the model can be validated experimentally. Thus, the model potentially affords a detailed mechanism to correlate intracellular transcriptional and physiological state with process performance, a capability that is valuable in an industrial setting.