Researchers at Harvard University have built a functional ribosome–the cell’s protein-making machine–from scratch, molecule by molecule. The creation represents a significant step toward making artificial life, and it could ultimately fill a major gap in our understanding of the origins of life. But the scientists who made the ribosome are most interested in its industrial applications. They plan to genetically tinker with the molecular machinery so that it can make proteins more efficiently, as well as proteins that are the mirror image of those ordinarily found in nature. Both improvements could be a major advantage in the pharmaceutical industry, among others.
To make the ribosomes, George Church, a Harvard geneticist, and postdoctoral researcher Mike Jewett first disassembled ribosomes from Escherichia coli, a common lab bacterium, into its component molecules. They then used enzymes to put the various RNA and protein components back together. When put together in a test tube, these components spontaneously formed into functional ribosomes. While scientists have previously reconstituted ribosomes, which are made up of a complex configuration of RNA and proteins, as far back as the 1960s, these earlier versions were poor protein producers, and were created under chemical conditions very different than that of a normal cell.
The researchers used the artificial ribosome to successfully produce the luciferase enzyme, a firefly protein that generates the bug’s glow. Eventually, says Church, he wants to create tiny protein factories out of tailor-made ribosomes. “We want to make large amounts of special proteins that are hard to make in vivo, and are useful for vaccine production [and other purposes].”
Next, the researchers want to create a ribosome that can re-create itself. They have compiled a list of 151 genes that they think are needed for a self-reproducing ribosome, including genes for ribosomal proteins, different types of RNAs, enzymes that catalyze different reactions in protein synthesis, and additional genes not directly related to the ribosome. “We think this is enough genes to replicate DNA, produce RNA and ribosomes, and have a primitive membrane,” says Church.”Once you get it going, it should be able to keep going if you supply it with amino acids and nucleotides [the building blocks of DNA and RNA].”
Once they get the system up and running, the researchers hope to genetically optimize it into an efficient protein factory. Protein products, such as biologic drugs, are now mostly made in vats of bacteria. “When you make proteins in live bacteria, you throw away 90 percent of the bacterial biomass just to get a few grams of protein,” says David Deamer, a chemist at the University of California, Santa Cruz. “If you could do it without live organisms, it could be much more efficient.”