YEAST genetically modified to add human sugars to proteins could soon be pumping out vast quantities of improved and novel drugs.
Many human proteins, such as growth hormone, are now mass-produced by vats of genetically modified bacteria or hamster cells. This avoids the risk of passing on diseases, which happened all too often when people were treated with proteins from animals or human corpses. But these cells either add no sugars at all or different ones to those found in humans.
And the sugars that adorn most human proteins can have a vital role. Synthetic antibodies, for example, would be much better at signalling to the immune system if they had the right sugar molecules.
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Proteins with the right sugars can be produced in human cells, of course, but the yields are very poor. Now GlycoFi of Lebanon, New Hampshire, has genetically engineered the yeast Pichia pastoris so that it adds human sugars to proteins. 鈥淲e鈥檝e essentially humanised the yeast,鈥� says Tillman Gerngross, the company鈥檚 chief scientist.
The team first deleted the gene that makes the yeast鈥檚 own protein sugars. Next, by adding a gene from nematodes, Gerngross forced the yeast to make short chains of mannose sugar units, the 鈥渂ase units鈥� of human sugars.
The final trick was to add two additional genes 鈥� one from humans and one from a fungus 鈥� that can embellish the 鈥渂ase鈥�, adding further sugar units such as galactose and sialic acid to create the tree-like sugar molecules found on human proteins.
GlycoFi has already created six strains of the yeast, each capable of adding a specific sugar 鈥渢ree鈥� to any protein, and hopes to have 30 by the end of the year. The company estimates that 100 or so strains would enable just about all known sugar arrangements on human proteins to be added. And, it claims, the yeast is extremely productive, producing protein yields 10 times as high as those of other cells. Details will appear in a forthcoming issue of the Proceedings of the National Academy of Sciences.