Quantitative proteomic analysis reveals a simple strategy of global resource allocation in bacteria

Abstract

A central aim of cell biology was to understand the strategy of gene expression in response to the environment. Here, we study gene expression response to metabolic challenges in exponentially growing Escherichia coli using mass spectrometry. Despite enormous complexity in the details of the underlying regulatory network, we find that the proteome partitions into several coarse-grained sectors, with each sector's total mass abundance exhibiting positive or negative linear relations with the growth rate. The growth rate-dependent components of the proteome fractions comprise about half of the proteome by mass, and their mutual dependencies can be characterized by a simple flux model involving only two effective parameters. The success and apparent generality of this model arises from tight coordination between proteome partition and metabolism, suggesting a principle for resource allocation in proteome economy of the cell. This strategy of global gene regulation should serve as a basis for future studies on gene expression and constructing synthetic biological circuits. Coarse graining may be an effective approach to derive predictive phenomenological models for other ‘omics’ studies.

Using cellular fitness to map the structure and function of a major facilitator superfamily effluxer

“…Additionally, we have omitted the binding of cytoplasmic drug [ S ] C to a ribosome. This competition for binding effectively acts to reduce the concentration of [ S ] C available to bind to the pump and is dependent on the growth rate (Klumpp & Hwa, 2014; Scott et al , 2014; Hui et al , 2015). Although this would affect any absolute estimates of binding rates (resulting in underestimates of k 1 ), it does not affect comparisons across TetB variants since the host strain remains unchanged.…”

A yield-cost tradeoff governs Escherichia coli's decision between fermentation and respiration in carbon-limited growth

“…http://dx.doi.org/10.1101/113183 doi: bioRxiv preprint first posted online Mar. 2, 2017; 2 the expense of catabolic, motility and biosynthetic proteins [1,10,28]. Similar changes are observed in cells subject to other modes of growth limitation, like nitrogen starvation or translational inhibition [10].…”

“…2, 2017; 2 the expense of catabolic, motility and biosynthetic proteins [1,10,28]. Similar changes are observed in cells subject to other modes of growth limitation, like nitrogen starvation or translational inhibition [10].In general terms, the problem of optimal proteome allocation can be posed as follows. Consider a generic cellular activity L described by a rate v L that is subject to limitation and such that µ is proportional to v L via a 'yield' Y representing the growth rate per unit of v L , so that µ = Y v L .…”

“…This strategy underlies e.g. an upregulated synthesis of transporters and catabolic proteins in response to a nutrient shortage, or an increase of the ribosomal proteome fraction in response to antibiotics, as seen for instance in [10].2. In addition, they can try to increase the growth yield Y (or, equivalently, decrease of the specific flux through the limited process, i.e.…”

“…However, the metabolic re-wiring required to increase Y necessarily implies the coordinated modulation of expression levels across multiple metabolic pathways. In the following we will aim at characterizing more precisely the trade-off that underlies such a re-organization.Proteome sectors in E. coli A consistent body of experimental work has shown that, in exponential growth, E. coli's proteome can be partitioned into "sectors" whose relative weights adjust with the growth conditions [1, 3,10]. At the simplest level, a four-way partition can be considered, in which three sectors [ribosome-affiliated proteins (R), metabolic enzymes (E) and proteins involved in the uptake system of the limiting nutrient (C)] respond to the growth rate µ, while a fourth sector (a core Q formed by housekeeping proteins) is µ-independent.…”