Sunday, April 29, 2007

Systems-level analysis of M. succiniciproducens MBEL55E by combined omics analyses

Seh Hee Jang, Hyohak Song, Jeong Wook Lee, and Sang Yup Lee. Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technolog, 373–1 Guseong–dong, Yuseong–gu, Daejeon, South Korea

Based on full genome sequence of Mannheimia succiniciproducens MBEL, DNA-chips having 2400 ORFs with 55 bp oligos were manufactured. Transcriptome analysis of M. succiniciproducens at the mid-exponential and early-stationary phases was conducted and those results were compared with proteome and fluxome result. As expected, transcriptome covered widest range of scope, 78% of fluxome and 97% of proteome data could be coupled to transcriptome data. The discrepancy between protein and RNA expression was observed, and the discordance was maximized for combined analysis of transcriptome and fluxome. The discrepancies of data among three omics must be consequent and provide invaluable information which cannot be obtained without integrated omics analyses. Highly wrought cellular regulatory mechanisms are working to optimize RNA and protein expression for optimal cellular activity under given limited condition. One example is protein cumulative effect caused by longer half-live of proteins than of that of RNAs. In case of fluxes, it has little relation with protein or RNA expression level since the flux is actual operating rate of the cell and strongly depends on nutrients up-take rate. All three omics data were combined and analyzed to obtain the direction of strain improvement for enhanced succinic production.
[This work was supported by the Genome-Based Integrated Bioprocess Project of the Ministry of Science and Technology. Further support by the LG Chem Chair Professorship, the IBM-SUR Program, Microsoft, and the KOSEF through the Center for Ultramicrochemical Process Systems is appreciated.]