TY - JOUR T1 - Laboratory evolution reveals a two-dimensional rate-yield tradeoff in microbial metabolism JF - bioRxiv DO - 10.1101/414912 SP - 414912 AU - Chuankai Cheng AU - Edward J. O’Brien AU - Douglas McCloskey AU - Jose Utrilla AU - Connor Olson AU - Ryan A. LaCroix AU - Troy E. Sandberg AU - Adam M. Feist AU - Bernhard O. Palsson AU - Zachary A. King Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/09/14/414912.abstract N2 - Growth rate and yield are fundamental features of micro-bial 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 trade-off 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 small-scale proteome allocation model with a 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 analysis of the genome-scale model shows that the rate-yield trade-offs that govern microbial adaptation to new environments are more complex than previously reported. ER -