A stochastic automaton shows how enzyme assemblies may contribute to metabolic efficiency

Patrick Amar,Vic Norris,Michel Thellier,Guillaume Legent,Thomas Nystrom,Gilles Bernot,Camille Ripoll,Milton H Saier

doi:10.1186/1752-0509-2-27

Abstract

BackgroundThe advantages of grouping enzymes into metabolons and into higher order structures have long been debated. To quantify these advantages, we have developed a stochastic automaton that allows experiments to be performed in a virtual bacterium with both a membrane and a cytoplasm. We have investigated the general case of transport and metabolism as inspired by the phosphoenolpyruvate:sugar phosphotransferase system (PTS) for glucose importation and by glycolysis.ResultsWe show that PTS and glycolytic metabolons can increase production of pyruvate eightfold at low concentrations of phosphoenolpyruvate. A fourfold increase in the numbers of enzyme EI led to a 40% increase in pyruvate production, similar to that observed in vivo in the presence of glucose. Although little improvement resulted from the assembly of metabolons into a hyperstructure, such assembly can generate gradients of metabolites and signaling molecules.Conclusionin silico experiments may be performed successfully using stochastic automata such as HSIM (Hyperstructure Simulator) to help answer fundamental questions in metabolism about the properties of molecular assemblies and to devise strategies to modify such assemblies for biotechnological ends.

Highlights

The advantages of grouping enzymes into metabolons and into higher order structures have long been debated
Equal numbers of enzymes in varying conditions of association The extent to which the assembly of enzymes into metabolons confers greater efficiency in a modified version of glycolysis and the phosphotransferase system (PTS) was the first question we addressed after testing HSIM
Glycolysis is modified because the real glycolytic pathway yields two PEPs per G6P which are converted into pyruvate by pyruvate kinase but it is not known how much of this PEP is available for the PTS in vivo, let alone how much is available in an individual cell

Summary

Introduction

The advantages of grouping enzymes into metabolons and into higher order structures have long been debated. To quantify these advantages, we have developed a stochastic automaton that allows experiments to be performed in a virtual bacterium with both a membrane and a cytoplasm. Investigation of glycolytic metabolons responsible for the metabolism of glucose has a long and controversial history [1,2], but it seems clear that in eukaryotes several of the glycolytic enzymes can form oligomers [3] and associate with other glycolytic enzymes [4,5]. The development of programs that allow genetic engineers to know in advance which constructions are worth making is biotechnology's equivalent of the quest for the Holy Grail

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Conclusion