Reconstituting ribosomes: Shown here is a parts list for creating a synthetic, self-replicating ribosome. Proteins are shown in purple, RNA in red, and DNA in blue. The list includes 54 ribosomal proteins, as well as RNA-based enzymes involved in protein production, and other molecules that interact with ribosomes.
Credit: George Church and Mike Jewett
Church and his team also want to use make modified ribosomes to make a new class of proteins–those that are the mirror image of the proteins found in nature. Proteins and many other molecules have a “handedness,” or chirality, to their structure. Amino acids made in nature are almost exclusively left-handed. And just as a glove fits on only one hand, left-handed enzymes can only catalyze reactions of substrates with the correct handedness. This means that mirror-image molecules would be resistant to breakdown by regular enzymes, says Church. That could have important industrial applications, generating long-lasting enzymes for biofermentation, used to create biofuels and other products.
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.”