Chemical Nursery - A Brief on Life's Beginnings

The origin of life is an especially difficult problem for chemistry because it is essentially unrestrained: there are a huge number of reactions that could have occurred on prebiotic Earth, and little hard limits on the types of compounds that could have been available, on the possible reaction conditions, and on the processes that could have eventually led to elementary cells of life. What is obvious, however, is the fundamental conundrum in understanding "life": that a living cell is made up of molecules; that molecules in cells react; that neither the molecules nor the reactions are alive in and of themselves; but that the cell is alive as a series of reactions and processes.

The core challenge of the field, and one of the major challenges of all of science, is figuring out how the transition happened - from an incomprehensibly large number of potential components to an aggregation of networks with an emergent property ("life"). The aim of this analysis is to obtain a deeper understanding of the potential reactions that may occur on the periodic Planet.

• Constrain the issue in order to clarify and concentrate the work of other scientists involved in creating the structurally complex molecules that are so important in today's world.

• Address some of the problems of concentration, catalysis, and network formation that are critical for the formation of spontaneously evolving dissipative systems.

• Compile plausible lists of elementary reactants and processes that lead to those commonly found in current metabolism.

• Develop rationales for the existence of "chemical fossils": molecules, reactions, and processes that have been preserved in the past.

The Chemical Origin of Networks

Several hypotheses of life's origins suggest that life evolved naturally from the self-assembly of organic reactions, which (im)probably happened chaotically in complex molecule mixtures. However, the chemistry that enables basic organic reactions to be assembled into networks of complex emergent behaviors is still unclear. We showed that molecular networks can exhibit fundamental system dynamics properties including bistability and oscillations.

The thiol network is the first experiment of organic molecules that may have occurred on the early Earth. This "network method" helps one to use chemistry to tune the intrinsic network mechanisms, and to use a reaction network's capacity to withstand oscillations (a mutual property of the network) as an observable behavior to investigate how networks of reactions coordinate, respond and develop in order to better understand the evolving concepts of existence through basic reactions. The ability to rationally construct molecular reaction networks may help researchers better understand the origins of life. We recently used a microreactor (a continuously stirred tank reactor, CSTR) to create a reaction network that could oscillate under continuous flow conditions, providing an elemental model for a protocell.

The oscillations are caused by three logical steps (i-ii, outlined in grey) in the network, which can be represented by a series of reactions and their corresponding time traces:

• A "triggering step" that releases the activator (ethanethiol), but is then blocked by a powerful inhibitor (maleimide). As a result, the inhibitor dosage produces a critical barrier that must be crossed, resulting in a latency step.

• "Auto-amplification," a process in which each ethanethiol is converted into two new thiols (cysteine and alanine mercaptoethyl amide), assisted by sulfide-disulfide exchange and Kent ligation. This autocatalytic reaction (or series of reactions) transforms cysteamine to an amide easily.

• "Termination," which happens when the majority of thiols produced are inhibited or exhausted. The battery is then recharged by adding reactants (indicated by the decrease followed by an increase in. Thiols are sequentially generated, ingested, and degraded under the right conditions, causing oscillations in their concentration over time. This mechanism does not specifically imitate metabolic processes (and is not meant to), but it is comparable in complexity to simple metabolic cycles, is simple to research (by looking at its oscillations), and does not use enzymatic catalysis (which could not have been present at the origins of metabolism).