Background: Elucidation of a genotype-phenotype relationship is critical to understand an organism at the whole-system level. Here, we demonstrate that comparative analyses of multi-omics data combined with a computational modeling approach provide a framework for elucidating the phenotypic characteristics of organisms whose genomes are sequenced.Results: We present a comprehensive analysis of genome-wide measurements incorporating multifaceted holistic data - genome, transcriptome, proteome, and phenome - to determine the differences between Escherichia coli B and K-12 strains. A genome-scale metabolic network of E. coli B was reconstructed and used to identify genetic bases of the phenotypes unique to B compared with K-12 through in silico complementation testing. This systems analysis revealed that E. coli B is well-suited for production of recombinant proteins due to a greater capacity for amino acid biosynthesis, fewer proteases, and lack of flagella. Furthermore, E. coli B has an additional type II secretion system and a different cell wall and outer membrane composition predicted to be more favorable for protein secretion. In contrast, E. coli K-12 showed a higher expression of heat shock genes and was less susceptible to certain stress conditions.Conclusions: This integrative systems approach provides a high-resolution system-wide view and insights into why two closely related strains of E. coli, B and K-12, manifest distinct phenotypes. Therefore, systematic understanding of cellular physiology and metabolism of the strains is essential not only to determine culture conditions but also to design recombinant hosts.
Bibliographical noteFunding Information:
The authors are grateful to Jeong Im Lee for contributing to the phenotype microarray experiment and other GEM members for technical assistance; Jong Shin Yoo for helping with the mass spectrometry analysis; F William Studier for critically reading the manuscript; and Sun Chang Kim, Ohsuk Kwon, Jae-Gu Pan, and Seung-Hwan Park for helpful comments and heartful support. Special gratitude also goes to the 21C Frontier Microbial Genomics and Applications Center for financial support for fabrication of DNA microarrays. This work was supported by the National Research Foundation of Korea (2011-0017670 to JFK), the Global Frontier Intelligent Synthetic Biology Center (2011-0031952 to SHY and 2011-0031963 to SYL), the 21C Frontier Microbial Genomics and Applications Center (to JFK), and the World Class University Program (to SYL) of the Ministry of Education, Science and Technology.
All Science Journal Classification (ASJC) codes
- Ecology, Evolution, Behavior and Systematics
- Cell Biology