Elucidating cell-free protein synthesis

The chemistry of life is complicated. Gene expression, in which information is transcribed from DNA to messenger RNA and then translated to produce a protein, involves more than 100 different molecules. Gaining a quantitative understanding of the process through observation of living cells is a daunting challenge. Now, Vincent Noireaux (University of Minnesota), Roy Bar-Ziv (Weizmann Institute of Science in Israel), and colleagues have used a cell-free system to carry out a complete gene-expression reaction, and they’ve developed a simple model of the reaction dynamics. Cell-free protein synthesis itself is not new; it’s been used for 15–20 years to produce proteins for research and medicine. Typical cell-free systems, which are available commercially, are therefore optimized to produce a lot of protein quickly rather than to reproduce reactions as they occur in vivo. The systems combine molecules from different organisms, and they don’t allow control over biologically important reactions such as mRNA inactivation and protein degradation. Noireaux and his student Jonghyeon Shin developed their own cell-free system, using molecules only from Escherichia coli bacteria and including enzymes for inactivation and degradation. Bar-Ziv and his student Eyal Karzbrun carried out experiments to determine how each component’s concentration affects the amount of protein produced. They found that they could describe the system’s main features by treating each process—transcription, translation, inactivation, and degradation—as if it were catalyzed by a single enzyme. The researchers’ next step is to extend the system to study more complicated processes, such as in circuits of several genes that affect one another’s expression. (E. Karzbrun et al., Phys. Rev. Lett., in press.)—Johanna Miller