RRC ID 53675
Author Link H, Fuhrer T, Gerosa L, Zamboni N, Sauer U.
Title Real-time metabolome profiling of the metabolic switch between starvation and growth.
Journal Nat Methods
Abstract Metabolic systems are often the first networks to respond to environmental changes, and the ability to monitor metabolite dynamics is key for understanding these cellular responses. Because monitoring metabolome changes is experimentally tedious and demanding, dynamic data on time scales from seconds to hours are scarce. Here we describe real-time metabolome profiling by direct injection of living bacteria, yeast or mammalian cells into a high-resolution mass spectrometer, which enables automated monitoring of about 300 compounds in 15-30-s cycles over several hours. We observed accumulation of energetically costly biomass metabolites in Escherichia coli in carbon starvation-induced stationary phase, as well as the rapid use of these metabolites upon growth resumption. By combining real-time metabolome profiling with modeling and inhibitor experiments, we obtained evidence for switch-like feedback inhibition in amino acid biosynthesis and for control of substrate availability through the preferential use of the metabolically cheaper one-step salvaging pathway over costly ten-step de novo purine biosynthesis during growth resumption.
Volume 12(11)
Pages 1091-7
Published 2015-11-1
DOI 10.1038/nmeth.3584
PII nmeth.3584
PMID 26366986
MeSH Adenosine Triphosphate / chemistry Amino Acids / chemistry Animals Bacillus subtilis Biomass Carbon / chemistry Cell Line Escherichia coli / physiology* Ions Kinetics Mass Spectrometry Metabolic Networks and Pathways Metabolome* Metabolomics / methods* Mice Models, Theoretical Purines / chemistry Saccharomyces cerevisiae Yersinia
IF 30.822
Times Cited 91
Prokaryotes E. coli