Emergence of diauxie as an optimal growth strategy under resource allocation constraints in cellular metabolism

Abstract

Diauxie, or the sequential consumption of carbohydrates in bacteria such as Escherichia coli, has been hypothesized to be an evolutionary strategy which allows the organism to maximize its instantaneous specific growth—giving the bacterium a competitive advantage. Currently, the computational techniques used in industrial biotechnology fall short of explaining the intracellular dynamics underlying diauxic behavior. In particular, the understanding of the proteome dynamics in diauxie can be improved. We developed a robust iterative dynamic method based on expression- and thermodynamically enabled flux models to simulate the kinetic evolution of carbohydrate consumption and cellular growth. With minimal modeling assumptions, we couple kinetic uptakes, gene expression, and metabolic networks, at the genome scale, to produce dynamic simulations of cell cultures. The method successfully predicts the preferential uptake of glucose over lactose in E. coli cultures grown on a mixture of carbohydrates, a manifestation of diauxie. The simulated cellular states also show the reprogramming in the content of the proteome in response to fluctuations in the availability of carbon sources, and it captures the associated time lag during the diauxie phenotype. Our models suggest that the diauxic behavior of cells is the result of the evolutionary objective of maximization of the specific growth of the cell. We propose that genetic regulatory networks, such as the lac operon in E. coli, are the biological implementation of a robust control system to ensure optimal growth.

AMiGA: Software for Automated Analysis of Microbial Growth Assays

“…We also developed a novel algorithm for the detection and characterization of multiphasic growth without any underlying assumptions of growth curve shape. Diauxie is a complex behavior characterized by two phases of growth that are often separated by a lag phase ( 1 , 14 , 34 ). There are no consensus formulations for diauxie, and current studies have relied on ad hoc analysis of growth data.…”

Changes in interactions over ecological time scales influence single cell growth dynamics in a metabolically coupled marine microbial community

“…Degrader cells in the mono-culture environment grow at higher rates in this secondary growth phase than individuals that experience a co-culture environment. The secondary growth phase can be explained by the reuptake of previously excreted metabolic byproducts and corresponds to the diauxic shift observed in various microbiological systems (31) (32).…”

A pair of isoleucyl-tRNA synthetases in Bacilli fulfill complementary roles to keep fast translation and provide antibiotic resistance

“…In contrast, in rich medium the strains did not show a difference in doubling times (Figure 6), nor did the ileS2 strain outcompete ileS1 (Figure 7B, right). However, in rich medium, both the WT and ileS2 strains displayed a noticeable lag at OD600 1.2, reminiscent of diauxic growth, often considered to provide a competitive advantage [24]: this phenotype was lost in the ileS1 strain (Figure 6).…”