Sung H Yoon1, Mee-Jung Han2,3, Haeyoung Jeong1, Choong H Lee1,4,5, Xiao-Xia Xia2, Dae-Hee Lee1, Ji H Shim1, Sang Y Lee2,6, Tae K Oh7 and Jihyun F Kim1,5*
1 Systems and Synthetic Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong, Daejeon 305-806, Korea
2 Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering, BioProcess Engineering Research Center, Center for Systems and Synthetic Biotechnology, and Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Yuseong, Daejeon 305-701, Korea
3 Department of Biomolecular and Chemical Engineering, Dongyang University, Yeongju, Gyeongbuk, 750-711, Korea
4Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Yuseong, Daejeon 305-701, Korea
5 Department of Systems Biology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Korea
6 Department of Bio and Brain Engineering, and Bioinformatics Research Center, Korea Advanced Institute of Science and Technology, Yuseong, Daejeon 305-701, Korea
7 21C Frontier Microbial Genomics and Applications Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong, Daejeon 305-806, Korea
* Corresponding author: Jihyun F Kim
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.
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.
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.