Boolean models of the transport, synthesis, and metabolism of tryptophan in Escherichia Coli

TL;DR

This paper develops Boolean models of tryptophan transport, synthesis, and metabolism in E. coli, capturing bistability and system behavior, and compares these models to previous differential equation approaches.

Contribution

It introduces a comprehensive Boolean modeling framework for the tryptophan system in E. coli, integrating transport, synthesis, and metabolism, and analyzes their dynamic properties.

Findings

Boolean models capture bistability in the tna operon.

Combined model shows loss of bistability, indicating homeostasis.

Long attractors in synchronous models are artifacts, absent in asynchronous models.

Abstract

The tryptophan (trp) operon in E. coli codes for the proteins responsible for the synthesis of the amino acid tryptophan from chorismic acid, and has been one of the most well-studied gene networks since its discovery in the 1960s. The tryptophanase (tna) operon codes for proteins needed to transport and metabolize it. Both of these have been modeled individually with delay differential equations under the assumption of mass-action kinetics. Recent work has provided strong evidence for bistable behavior of the tna operon. The authors of (Orozco, 2019) identified a medium range of tryptophan in which the system has two stable steady-states, and they reproduced these experimentally. In this paper, we will show how a Boolean model can capture this bistability. We will also develop and analyze a Boolean model of the trp operon. Finally, we will combine these two to create a single Boolean model of the transport, synthesis, and metabolism of tryptophan. In this amalgamated model, the bistability disappears, presumably reflecting the ability of the trp operon to produce tryptophan and drive the system toward homeostasis. All of these models have longer attractors that we call "artifacts of synchrony", which disappear in the asynchronous automata. This curiously matches the behavior of a recent Boolean model of the arabinose operon in E. coli, and we discuss some open-ended questions that arise along these lines.