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.
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We thank Albert Libchaber and Norman Packard for their advices and critical reading of the manuscript. This research was supported by the Office of Naval Research award number N00014-13-1-0074.