Comparative multi-omics systems analysis of Escherichia coli strains B and K-12.
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.
Systems and Synthetic Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong, Daejeon 305-806, Korea.
Sung Ho
SH
Yoon
Mee-Jung
MJ
Han
Haeyoung
H
Jeong
Choong Hoon
CH
Lee
Xiao-Xia
XX
Xia
Dae-Hee
DH
Lee
Ji Hoon
JH
Shim
Sang Yup
SY
Lee
Tae Kwang
TK
Oh
Jihyun F
JF
Kim
D004926:Escherichia coli / Q000145:classification / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D056726:Genetic Association Studies; D016680:Genome, Bacterial; D023281:Genomics; D006038:Glyoxylates / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D029968:Escherichia coli Proteins; D006038:Glyoxylates; D020543:Proteome; D011994:Recombinant Proteins; C031150:glyoxylic acid