A key requirement of an autonomous self-replicating molecular machine, a protocell, is the ability to digest resources and turn them into building blocks. Thus a protocell needs a set of metabolic processes fueled by external free energy in the form of available chemical redox potential or light. We introduce and investigate a minimal photodriven metabolic system, which is based on photofragmentation of resource molecules catalyzed by genetic molecules. We represent and analyze the full metabolic set of reaction-kinetic equations and, through a set of approximations, simplify the reaction kinetics so that analytical expressions can be obtained for the building block production. The analytical approximations are compared with the full equation set and with corresponding experimental results to the extent they are available. It should be noted, however, that the proposed metabolic system has not been experimentally implemented, so this investigation is conducted to obtain a deeper understanding of its dynamics and perhaps to anticipate its limitations. We demonstrate that this type of minimal photodriven metabolic scheme is typically rate-limited by the front-end photoexcitation process, while its yield is determined by the genetic catalysis. We further predict that gene-catalyzed metabolic reactions can undergo evolutionary selection only for certain combinations of the involved reaction rates due to their intricate interactions. We finally discuss how the expected range of metabolic rates likely affects other key protocellular processes such as container growth and division as well as gene replication.
Assembling non-biological materials (geomaterials) into a proto-organism constitutes a bridge between nonliving and living matter. In this article we present a simple step-by-step route to assemble a proto-organism. Many pictures have been proposed to describe this transition within the origins-of-life and artificial life communities, and more recently alternative pictures have been emerging from advances in nanoscience and biotechnology. The proposed proto-organism lends itself to both traditions and defines a new picture based on a simple idea: Given a set of required functionalities, minimize the physicochemical structures that support these functionalities, and make sure that all structures self-assemble and mutually enhance each other's existence. The result is the first concrete, rational design of a simple physicochemical system that integrates the key functionalities in a thermodynamically favorable manner as a lipid aggregate integrates proto-genes and a proto-metabolism. Under external pumping of free energy, the metabolic processes produce the required building blocks, and only specific gene sequences enhance the metabolic kinetics sufficiently for the whole system to survive. We propose an experimental implementation of the proto-organism with a discussion of our experimental results, together with relevant results produced by other experimental groups, and we specify what is still missing experimentally. Identifying the missing steps is just as important as providing the road map for the transition. We derive the kinetic and thermodynamic conditions of each of the proto-organism subsystems together with relevant theoretical and computational results about these subsystems. We present and discuss detailed 3D simulations of the lipid aggregation processes. From the reaction kinetics we derive analytical aggregate size distributions, and derive key properties of the metabolic efficiency and stability. Thermodynamics and kinetics of the ligation directed self-replication of the proto-genes is discussed, and we summarize the full life cycle of the proto-organism by comparing size, replication time, and energy with the biomass efficiency of contemporary unicells. Finally, we also compare our proto-organism picture with existing origins-of-life and protocell pictures. By assembling one possible bridge between nonliving and living matter we hope to provide a piece in the ancient puzzle about who we are and where we come from.