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Self-regeneration is a fundamental function of all living systems. Here we demonstrate partial molecular self-regeneration in a synthetic cell. By implementing a minimal transcription-translation system within microfluidic reactors, the system is able to regenerate essential protein components from DNA templates and sustain synthesis activity for over a day. By quantitating genotype-phenotype relationships combined with computational modeling we find that minimizing resource competition and optimizing resource allocation are both critically important for achieving robust system function. With this understanding, we achieve simultaneous regeneration of multiple proteins by determining the required DNA ratios necessary for sustained self-regeneration. This work introduces a conceptual and experimental framework for the development of a self-replicating synthetic cell. A fundamental function of living systems is regenerating essential components. Here the authors design an artificial cell using a minimal transcription-translation system in microfluidic reactors for sustained regeneration of multiple essential proteins.
Didier Trono, Henning Paul-Julius Stahlberg, Beat Fierz, Priscilla Turelli, Bruno Emanuel Ferreira De Sousa Correia, Elisa Oricchio, Sandrine Madeleine Suzanne Georgeon, Dongchun Ni, Michael Bronstein, Pablo Gainza Cirauqui, Zander Harteveld, Andreas Scheck, Charlène Mireille Raymonde Raclot, Anthony Marchand, Alexandra Teslenko, Casper Alexander Goverde, Aaron Simone Petruzzella, Stephen Michael Buckley, Martin Pacesa, Stéphane Rosset, Sarah Wehrle, Freyr Sverrisson, Alexandra Krina Van Hall-Beauvais, Jane Marsden