Laboratory evolution reveals a two-dimensional rate-yield tradeoff in microbial metabolism

Abstract

Growth rate and yield are fundamental features of microbial growth. However, we lack a mechanistic and quantitative understanding of the rate-yield relationship. Studies pairing computational predictions with experiments have shown the importance of maintenance energy and proteome allocation in explaining rate-yield tradeoffs and overflow metabolism. Recently, adaptive evolution experiments of Escherichia coli reveal a phenotypic diversity beyond what has been explained using simple models of growth rate versus yield. Here, we identify a two-dimensional rate-yield tradeoff in adapted E. coli strains where the dimensions are (A) a tradeoff between growth rate and yield and (B) a tradeoff between substrate (glucose) uptake rate and growth yield. We employ a multi-scale modeling approach, combining a previously reported coarse-grained small-scale proteome allocation model with a fine-grained genome-scale model of metabolism and gene expression (ME-model), to develop a quantitative description of the full rate-yield relationship for E. coli K-12 MG1655. The multi-scale analysis resolves the complexity of ME-model which hindered its practical use in proteome complexity analysis, and provides a mechanistic explanation of the two-dimensional tradeoff. Further, the analysis identifies modifications to the P/O ratio and the flux allocation between glycolysis and pentose phosphate pathway (PPP) as potential mechanisms that enable the tradeoff between glucose uptake rate and growth yield. Thus, the rate-yield tradeoffs that govern microbial adaptation to new environments are more complex than previously reported, and they can be understood in mechanistic detail using a multi-scale modeling approach.

Evolution of Pseudomonas aeruginosa toward higher fitness under standard laboratory conditions

“…Moreover, roughly half of the P. aeruginosa WBN clones developed higher cell densities in stationary phase, despite a lack of selection for this trait. In the majority of WBN clones, we observed a positive correlation between the growth rate and yield, which distinguished our results from the previous observations of a trade-off between growth rate and growth yield in bacteria characterized by faster growth [50][51][52][53][54][55][56]. Nevertheless, in one of the lines (WBN2 cell line) there was evidence for a growth rate/yield trade-off as predicted previously [57].…”

Global pleiotropic effects in adaptively evolvedEscherichia colilacking CRP reveal molecular mechanisms that define growth physiology

“…S18D). This phenomenon of lowered efficiency of carbon substrate allocation towards growth reinforced the rate-yield trade-off mechanism prevalent in ALE-adapted strains (Cheng et al, 2019).…”

Carbon Use Efficiency and Its Temperature Sensitivity Covary in Soil Bacteria

“…For example, selection for rapid growth in Escherichia coli can result in either a high-uptake, low-yield phenotype or a moderate-uptake, high-yield phenotype (31). Rather, the growth rate-yield trade-off does not act alone to determine efficiency and instead acts in concert with a second axis describing the relationship between substrate uptake rate and yield (53). As a result, the ubiquity of overflow metabolism-oft cited as a cause for the rate yield trade-off-is uncertain, as not all organisms shift away from the pentose phosphate pathway and toward glycolysis when grown on glucose (53).…”

“…Rather, the growth rate-yield trade-off does not act alone to determine efficiency and instead acts in concert with a second axis describing the relationship between substrate uptake rate and yield (53). As a result, the ubiquity of overflow metabolism-oft cited as a cause for the rate yield trade-off-is uncertain, as not all organisms shift away from the pentose phosphate pathway and toward glycolysis when grown on glucose (53). Since we found a similar pattern of CUE increasing with growth rate and rrN even for nonfermentable substrates, this indicates that overflow metabolism was not a uniform driver of CUE and yield at high growth rates in our environmental isolates.…”