RRC ID 53674
Author Gerosa L, Haverkorn van Rijsewijk BR, Christodoulou D, Kochanowski K, Schmidt TS, Noor E, Sauer U.
Title Pseudo-transition Analysis Identifies the Key Regulators of Dynamic Metabolic Adaptations from Steady-State Data.
Journal Cell Syst
Abstract Hundreds of molecular-level changes within central metabolism allow a cell to adapt to the changing environment. A primary challenge in cell physiology is to identify which of these molecular-level changes are active regulatory events. Here, we introduce pseudo-transition analysis, an approach that uses multiple steady-state observations of (13)C-resolved fluxes, metabolites, and transcripts to infer which regulatory events drive metabolic adaptations following environmental transitions. Pseudo-transition analysis recapitulates known biology and identifies an unexpectedly sparse, transition-dependent regulatory landscape: typically a handful of regulatory events drive adaptation between carbon sources, with transcription mainly regulating TCA cycle flux and reactants regulating EMP pathway flux. We verify these observations using time-resolved measurements of the diauxic shift, demonstrating that some dynamic transitions can be approximated as monotonic shifts between steady-state extremes. Overall, we show that pseudo-transition analysis can explore the vast regulatory landscape of dynamic transitions using relatively few steady-state data, thereby guiding time-consuming, hypothesis-driven molecular validations.
Volume 1(4)
Pages 270-82
Published 2015-10-28
DOI 10.1016/j.cels.2015.09.008
PII S2405-4712(15)00146-5
PMID 27136056
IF 8.982
Resource
Prokaryotes E. coli