Constraints on Metabolic Network Analysis in Bacterial Physiology

Abstract

In biology, data are conceptualized using diagrams that capture protein-protein, enzyme-substrate, and regulator-target interactions, among many others. These interaction diagrams are every bit as complicated as wiring diagrams in modern electronic circuits—in many cases, even more so. Yet, in contrast to electronic circuits, living systems must also autonomously reproduce; some part of the “wiring diagram” of life must be devoted to reproducing itself. A greatly simplifying principle in the analysis of these biological wiring diagrams is that of “balanced growth,” in which network flows are balanced according to the requirements of biomass production, leading to the exponential accumulation of cells. In microbial cells, exponential growth greatly simplifies the underlying biochemical networks, because when its mathematical description is combined with kinetic descriptions of underlying enzyme-mediated reactions, macroscale constraints on physiology emerge. As is demonstrated in this tutorial, these constraints are mathematically and conceptually equivalent to Kirchhoff's circuit laws and Ohm's constitutive equation. Consequently, bacterial growth physiology can be approached with the same quantitative rigour as electrical circuit analysis. In this tutorial, this “Ohmics” approach is developed in detail, and its power in simplifying complex physiology is demonstrated through two case studies.