Novel proteins, created from scratch with no particular design in mind, can sometimes do the work of a natural protein. The discovery may widen the toolkit of synthetic biologists trying to build bespoke organisms. There are more proteins possible than there are atoms in the universe, and yet evolution has tested only a minuscule fraction of them. No one knows whether the vast, untried space of proteins includes some that could have biological uses. Until now, most researchers assembling novel proteins have meticulously selected each amino acid building block so that the resulting protein folds precisely into a pre-planned shape that closely fits the molecules it is intended to interact with.
Proteins are the workhorses of all living creatures, fulfilling the instructions of DNA. They occur in a wide variety of complex structures and carry out all the important functions in our body and in all living organisms--digesting food, building tissue, transporting oxygen through the bloodstream, dividing cells, firing neurons, and powering muscles. Remarkably, this versatility comes from different combinations, or sequences, of just 20 amino acid molecules. How these linear sequences fold up into complex structures is just now beginning to be well understood. Even more remarkably, nature seems to have made use of only a tiny fraction of the potential protein structures available--and there are many.
Gene therapy generally relies on delivering DNA into cells along with strategies to control its expression. Synthetic messenger RNA (mRNA) is an attractive alternative gene therapy vehicle for applications that require transient protein expression, but controlling this expression remains challenging. One approach is to add a degradation domain to the protein, but this may compromise its proper function. Wagner et al. engineered small-molecule-responsive RNA binding proteins (RBPs) to control expression of proteins from synthetic mRNA. By regulating binding of the RBPs, they can regulate the timing and magnitude of expression of reporter proteins in engineered circuits that use either synthetic RNAs with base modifications (modRNA) designed to decrease immunogenicity or self-replicating RNAs (replicons) that give high levels of expression.
"What we are now able to demonstrate offers fantastic potential for a number of future applications, such as faster and more cost-efficient development of protein-based drugs," says Aleksej Zelezniak, Associate Professor at the Department of Biology and Biological Engineering at Chalmers. Proteins are large, complex molecules that play a crucial role in all living cells, building, modifying, and breaking down other molecules naturally inside our cells. They are also widely used in industrial processes and products, and in our daily lives. Protein-based drugs are very common--the diabetes drug insulin is one of the most prescribed. Some of the most expensive and effective cancer medicines are also protein-based, as well as the antibody formulas currently being used to treat COVID-19.
Chinese researchers say they have developed the technology to turn industrial emissions into animal feed at scale, a move that could cut the country's dependence on imported raw materials such as soybeans. The technology involves synthesizing industrial exhaust containing carbon monoxide, carbon dioxide and nitrogen into proteins using Clostridium autoethanogenum, a bacteria used to make ethanol. The news was reported this week in the state-run Science and Technology Daily. China is the top importer of soybeans, which are crushed to produce meal -- mainly to feed its pig herd, the largest globally. It buys huge volumes from countries including Brazil, Argentina and the U.S. The commodity has also been a major source of friction contributing to U.S.-China trade tensions.