Understanding and controlling complex biomolecular systems is critical for investigating natural biological phenomena, for treating disease, and for engineering biology. Achieving this task is not straight-forward. Biological systems are complicated. They are built from highly integrative and non-linear networks of constantly changing molecular players. To truly test our understanding of complex biomolecular systems and have complete control over the behavior of constituent parts, we must learn how to build integrated biological processes from their fundamental components. We must learn how to build synthetic cells from the bottom-up. Since ribosomes are central for protein synthesis and cellular function, understanding and replicating ribosome biogenesis in cell-free systems is the critical milestone for building synthetic cells. Here, we review past efforts, current challenges, and future directions for cell-free ribosome biogenesis. We highlight the need for standardized metrics for ribosome assembly and function, mechanistic models, and integration with other cell-free optimizations. Furthermore, we discuss the potential impact of cell-free ribosome biogenesis as a strategic target for fields beyond synthetic cells and cell-free systems, such as ribosome engineering, synthetic biology, basic science, materials science, health science, and the study of the origin of life.
Mohamed Soufi (Sun,) studied this question.