Integration of biological parts toward the synthesis of a minimal cell

• Minimal cell modular design: information, self-organization, and metabolism.
• Components encapsulation in cell-sized liposome.
• Self-sustained system through cell-free metabolism based on carbon sources and active membrane.
• Self-reproduction and volume expansion driven by DNA programs.
• Integration of biological parts and modules accelerated by high-throughput experimentation and machine learning.

Various approaches are taken to construct synthetic cells in the laboratory, a challenging goal that became experimentally imaginable over the past two decades. The construction of protocells, which explores scenarios of the origin of life, has been the original motivations for such projects. With the advent of the synthetic biology era, bottom-up engineering approaches to synthetic cells are now conceivable. The modular design emerges as the most robust framework to construct a minimal cell from natural molecular components. Although significant advances have been made for each piece making this complex puzzle, the integration of the three fundamental parts, information–metabolism–self-organization, into cell-sized liposomes capable of sustained reproduction has failed so far. Our inability to connect these three elements is also a major limitation in this research area. New methods, such as machine learning coupled to high-throughput techniques, should be exploited to accelerate the cell-free synthesis of complex biochemical systems.