The power of biological systems can be harnessed with higher efficiency when biosynthetic reactions are decoupled from cellular physiology. This can be achieved by cell-free synthesis, which relies on the in vitro use of cellular machinery under optimized reaction conditions. As exemplified by the recent development of mRNA vaccines and therapeutics, the cell-free synthesis of biomolecules is fast, efficient and flexible. Cell-free synthesis of industrial chemicals and biofuels is drawing considerable attention as a promising alternative to microbial fermentation processes, which currently show low conversion yields and toxicity to host cells. Here, we provide a brief overview of the history of cell-free synthesis systems and the state-of-the-art cell-free technologies used to produce diverse chemicals and biofuels. We also discuss the future directions of cell-free synthesis that can fully harness the synthetic power of biological systems.
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