Autocatalytic, bistable, oscillatory networks of biologically relevant organic reactions.

Jerome M. Fox,Lewis J. Kraft,Sergey N. Semenov,Victoria E. Campbell,Alar Ainla,Mengxia Zhao,Mostafa Baghbanzadeh,George M. Whitesides,Kyungtae Kang

doi:10.1038/nature19776

Abstract

Networks of organic chemical reactions are important in life and probably played a central part in its origin. Network dynamics regulate cell division, circadian rhythms, nerve impulses and chemotaxis, and guide the development of organisms. Although out-of-equilibrium networks of chemical reactions have the potential to display emergent network dynamics such as spontaneous pattern formation, bistability and periodic oscillations, the principles that enable networks of organic reactions to develop complex behaviours are incompletely understood. Here we describe a network of biologically relevant organic reactions (amide formation, thiolate-thioester exchange, thiolate-disulfide interchange and conjugate addition) that displays bistability and oscillations in the concentrations of organic thiols and amides. Oscillations arise from the interaction between three subcomponents of the network: an autocatalytic cycle that generates thiols and amides from thioesters and dialkyl disulfides; a trigger that controls autocatalytic growth; and inhibitory processes that remove activating thiol species that are produced during the autocatalytic cycle. In contrast to previous studies that have demonstrated oscillations and bistability using highly evolved biomolecules (enzymes and DNA) or inorganic molecules of questionable biochemical relevance (for example, those used in Belousov-Zhabotinskii-type reactions), the organic molecules we use are relevant to metabolism and similar to those that might have existed on the early Earth. By using small organic molecules to build a network of organic reactions with autocatalytic, bistable and oscillatory behaviour, we identify principles that explain the ways in which dynamic networks relevant to life could have developed. Modifications of this network will clarify the influence of molecular structure on the dynamics of reaction networks, and may enable the design of biomimetic networks and of synthetic self-regulating and evolving chemical systems.

Highlights

We describe a network of biologically relevant organic reactions that displays bistability and oscillations in concentrations of organic thiols and amides
In contrast to previous studies demonstrating oscillations and bistability using highly evolved biomolecules or inorganic molecules of questionable biochemical relevance,[18,19] the organic molecules used in our network are relevant to current metabolism and similar to those that might have existed on early Earth
By using small organic molecules to build a network of organic reactions with autocatalytic, bistable, and oscillatory behavior, we identified principles that clarify how dynamic networks relevant to life might possibly have developed

Summary

Introduction

To test the ability of maleimide to delay autocatalytic growth, we added 5 mol % of this molecule to a mixture of CSSC and AlaSEt (in batch), and used proton nuclear magnetic resonance (1H NMR) to monitor both the production of alanine amides and the disappearance of maleimide by (Fig. 2b and Extended Data Fig. 3a-c). To test our reaction network under flow conditions, we constructed a small CSTR and connected it to a spectrophotometer to monitor the total concentration of thiols in the system continuously (Fig. 3, Extended Data Fig. 4).

Results

Conclusion