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Laboratory evolution reveals a two-dimensional rate-yield tradeoff in microbial metabolism
Author(s) -
Chuankai Cheng,
Edward J. O’Brien,
Douglas McCloskey,
José Utrilla,
Connor A. Olson,
Ryan A. LaCroix,
Troy E. Sandberg,
Adam M. Feist,
Bernhard Ø. Palsson,
Zachary A. King
Publication year - 2019
Publication title -
plos computational biology/plos computational biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.628
H-Index - 182
eISSN - 1553-7358
pISSN - 1553-734X
DOI - 10.1371/journal.pcbi.1007066
Subject(s) - yield (engineering) , growth rate , proteome , biological system , biology , computational biology , flux (metallurgy) , systems biology , biochemical engineering , biochemistry , chemistry , mathematics , thermodynamics , geometry , organic chemistry , engineering , physics
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.

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