Cell-free biosystems for biomanufacturing

Although cell-free biosystems have been used as a tool for investigating fundamental aspects of biological systems for more than 100 years, they are becoming an emerging biomanufacturing platform in the production of low-value biocommodities (e.g., H(2), ethanol, and isobutanol), fine chemicals, and high-value protein and carbohydrate drugs and their precursors. Here we would like to define the cell-free biosystems containing more than three catalytic components in a single reaction vessel, which although different from one-, two-, or three-enzyme biocatalysis can be regarded as a straightforward extension of multienzymatic biocatalysis. In this chapter, we compare the advantages and disadvantages of cell-free biosystems versus living organisms, briefly review the history of cell-free biosystems, highlight a few examples, analyze any remaining obstacles to the scale-up of cell-free biosystems, and suggest potential solutions. Cell-free biosystems could become a disruptive technology to microbial fermentation, especially in the production of high-impact low-value biocommodities mainly due to the very high product yields and potentially low production costs.