Scientists have bioengineered yeast to produce large amounts of proteins that contain amino acids not found in nature. Proteins with unnatural amino acids (UAAs) are a potential source of new drugs with novel properties.
There are only 20 naturally occurring amino acids and they produce a vast array of proteins with a huge range of different functions. Up until now, it was only possible to produce large amounts of UAA-containing proteins in bacteria. But, US researchers from the Salk Institute for Biological Studies, California have created a super yeast capable of producing 300 times more UAA-containing proteins than ordinary yeast.
They did this by replacing part of the yeast’s protein manufacturing system with a part of Escherichia coli’s machinery that is extremely efficient at recruiting unnatural amino acids. They also shut off the part of the yeast’s quality control mechanisms that weeds out protein blueprints that contain early stop signals. UAAs need to use amino acid addresses that are unused by natural amino acids and a signal to stop making protein is often used as there are several of these available. The researchers selected for yeast that ignored these early stop signals (JACS 2008, 130, 6066).
Author Lei Wang said: ‘Producing UAA-containing proteins in yeast will enable us to introduce new chemical or physical properties into these proteins, so that we can enhance the biological function or create new protein function.’ There are no proteins with artificial amino acids in use yet but they are being investigated, and UAAs can give protein drugs useful characteristics such as longer half lives. Some proteins can only be produced in higher organisms like yeast so this system could be very useful to the biotech industry, Wang says.
Heinz Neumann, a UAA researcher at the MRC Laboratory of Molecular Biology in the UK, says that this yeast will be a very useful tool for studying how proteins interact in vivo. However, he says that these numbers should be taken with a pinch of salt but even a ten-fold increase in the amount UAA protein produced would be a welcome development.