Compartmentalised chemistry: from studies on the origin of life to engineered biochemical systems

Abstract

The origin of life on Earth has been the subject of inquiry since the early days of philosophical thought. The main questions are centred around the formation of protocells capable of metabolism and replication. Research studies have been carried out to simulate the conditions on early Earth. They have led to a proposal that the first cells could have emerged through self-assembly of molecules such as phospholipids. When such structures split pre-metabolic mixtures into small-volume aliquots, biochemical reactions could be “digitised” giving rise to self-sustaining entities. Since then compartmentalisation has remained instrumental to biology and biochemistry. It prevents dispersion of metabolic intermediates, and facilitates molecular interactions by means of confinement. Eukaryotic organisms are highly compartmentalised on various levels (subcellular, cellular, and organ levels). Apart from cell-level compartmentalisation, metabolism relies on the separation of biochemical pathways into subcellular organelles. Whilst in vitro studies in chemical and synthetic biology generally use homogeneous mixtures of reactants and biocatalysts, a faithful mimicry of biochemical systems requires introduction of metabolic compartments. In fact, the compartmentalised structure of biological tissues can serve as a blueprint in applied research (e.g. biochemical engineering). Three-dimensional arrays of interconnected microdroplet compartments can already be engineered. It is envisioned that compartmentalisation will play a key role in emerging biotechnologies, including those related to in vitro growth of tissues and organs, offering new possibilities in regenerative medicine, as well as the construction of intelligent and miniaturised systems for multi-step biosyntheses and biocomputing.