BACKGROUND: Chaperonins are important in living systems because they play a role 
in the folding of proteins. Earlier comprehensive analyses identified substrate 
proteins for which folding requires the chaperonin GroEL/GroES (GroE) in 
Escherichia coli, and they revealed that many chaperonin substrates are 
metabolic enzymes. This result implies the importance of chaperonins in 
metabolism. However, the relationship between chaperonins and metabolism is 
still unclear.
RESULTS: We investigated the distribution of chaperonin substrate enzymes in the 
metabolic network using network analysis techniques as a first step towards 
revealing this relationship, and found that as chaperonin requirement increases, 
substrate enzymes are more laterally distributed in the metabolic. In addition, 
comparative genome analysis showed that the chaperonin-dependent substrates were 
less conserved, suggesting that these substrates were acquired later on in 
evolutionary history.
CONCLUSIONS: This result implies the expansion of metabolic networks due to this 
chaperonin, and it supports the existing hypothesis of acceleration of evolution 
by chaperonins. The distribution of chaperonin substrate enzymes in the 
metabolic network is inexplicable because it does not seem to be associated with 
individual protein features such as protein abundance, which has been observed 
characteristically in chaperonin substrates in previous works. However, it 
becomes clear by considering this expansion process due to chaperonin. This 
finding provides new insights into metabolic evolution and the roles of 
chaperonins in living systems.