title: Transcriptional regulation is insufficient to explain substrate-induced flux changes in Bacillus subtilis.
abstract: One of the key ways in which microbes are thought to regulate their metabolism is by modulating the availability of enzymes through transcriptional regulation. However, the limited success of efforts to manipulate metabolic fluxes by rewiring the transcriptional network has cast doubt on the idea that transcript abundance controls metabolic fluxes. In this study, we investigate control of metabolic flux in the model bacterium Bacillus subtilis by quantifying fluxes, transcripts, and metabolites in eight metabolic states enforced by different environmental conditions. We find that most enzymes whose flux switches between on and off states, such as those involved in substrate uptake, exhibit large corresponding transcriptional changes. However, for the majority of enzymes in central metabolism, enzyme concentrations were insufficient to explain the observed fluxes--only for a number of reactions in the tricarboxylic acid cycle were enzyme changes approximately proportional to flux changes. Surprisingly, substrate changes revealed by metabolomics were also insufficient to explain observed fluxes, leaving a large role for allosteric regulation and enzyme modification in the control of metabolic fluxes.
authors.affiliation: Institute of Molecular System Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Victor
authors.initials: V
authors.lastname: Chubukov
authors.forename: Markus
authors.initials: M
authors.lastname: Uhr
authors.forename: Ludovic
authors.initials: L
authors.lastname: Le Chat
authors.forename: Roelco J
authors.initials: RJ
authors.lastname: Kleijn
authors.forename: Matthieu
authors.initials: M
authors.lastname: Jules
authors.forename: Hannes
authors.initials: H
authors.lastname: Link
authors.forename: Stephane
authors.initials: S
authors.lastname: Aymerich
authors.forename: Jörg
authors.initials: J
authors.lastname: Stelling
authors.forename: Uwe
authors.initials: U
authors.lastname: Sauer
mesh_terms: D001412:Bacillus subtilis / Q000201:enzymology* / Q000235:genetics*; D002247:Carbon Isotopes; D015964:Gene Expression Regulation, Bacterial; D007700:Kinetics; D053858:Metabolic Networks and Pathways; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002247:Carbon Isotopes; D012333:RNA, Messenger