TY - JOUR
T1 - Global metabolic network reorganization by adaptive mutations allows fast growth of Escherichia coli on glycerol
AU - Cheng, Kian Kai
AU - Lee, Baek Seok
AU - Masuda, Takeshi
AU - Ito, Takuro
AU - Ikeda, Kazutaka
AU - Hirayama, Akiyoshi
AU - Deng, Lingli
AU - Dong, Jiyang
AU - Shimizu, Kazuyuki
AU - Soga, Tomoyoshi
AU - Tomita, Masaru
AU - Palsson, Bernhard O.
AU - Robert, Martin
PY - 2014/1/31
Y1 - 2014/1/31
N2 - Comparative whole-genome sequencing enables the identification of specific mutations during adaptation of bacteria to new environments and allelic replacement can establish their causality. However, the mechanisms of action are hard to decipher and little has been achieved for epistatic mutations, especially at the metabolic level. Here we show that a strain of Escherichia coli carrying mutations in the rpoC and glpK genes, derived from adaptation in glycerol, uses two distinct metabolic strategies to gain growth advantage. A 27-bp deletion in the rpoC gene first increases metabolic efficiency. Then, a point mutation in the glpK gene promotes growth by improving glycerol utilization but results in increased carbon wasting as overflow metabolism. In a strain carrying both mutations, these contrasting carbon/energy saving and wasting mechanisms work together to give an 89% increase in growth rate. This study provides insight into metabolic reprogramming during adaptive laboratory evolution for fast cellular growth.
AB - Comparative whole-genome sequencing enables the identification of specific mutations during adaptation of bacteria to new environments and allelic replacement can establish their causality. However, the mechanisms of action are hard to decipher and little has been achieved for epistatic mutations, especially at the metabolic level. Here we show that a strain of Escherichia coli carrying mutations in the rpoC and glpK genes, derived from adaptation in glycerol, uses two distinct metabolic strategies to gain growth advantage. A 27-bp deletion in the rpoC gene first increases metabolic efficiency. Then, a point mutation in the glpK gene promotes growth by improving glycerol utilization but results in increased carbon wasting as overflow metabolism. In a strain carrying both mutations, these contrasting carbon/energy saving and wasting mechanisms work together to give an 89% increase in growth rate. This study provides insight into metabolic reprogramming during adaptive laboratory evolution for fast cellular growth.
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U2 - 10.1038/ncomms4233
DO - 10.1038/ncomms4233
M3 - Article
C2 - 24481126
AN - SCOPUS:84928889593
VL - 5
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 3233
ER -