Humanised yeast produce healing proteins

HELEN PEARSON

Yeast cells grow faster and more easily than mammalian cells © SPL

A humanised yeast that pumps out medicinal proteins could simplify drug manufacture.

Human proteins are increasingly used as medicines - erythropoietin for example, bolsters flagging red blood cells after cancer. But many, called glycoproteins, must be reaped from mammalian cells if they are to contain vital sugar molecules. This harvesting is expensive and inefficient.

So Tillman Gerngross of Dartmouth College in Hanover, New Hampshire and his coworkers have tweaked yeast cells to attach human sugar molecules to a protein. "You put in a human gene and it'll make a human protein," he says.

Since yeast grow faster and need less tending than mammalian cells, they could make the manufacture of human proteins cheaper and easier. Already human insulin for diabetics, which does not need added sugars, is brewed from yeast in this way.

One day, production of human antibodies such as herceptin for breast cancer, plus countless others under development, might switch into yeast. "It's a huge advance," says Carolyn Bertozzi who studies glycoproteins at the University of California at Berkeley. "They've done a heroic engineering experiment".

Yeast-assembled proteins may also be safer. Yeast make only one shape of glycoprotein, whereas mammalian cells churn out a cocktail, explains biochemist Laura Kiessling of the University of Wisconsin, Madison. Each variant may stick to cells or breakdown differently so that the mixture is less predictable.

No added sugar

Enzymes in human cells attach sugars to new proteins, then prune and elaborate on them. Because yeast affix different sugars to their glycoproteins, their molecules normally trigger an immune reaction in people. Bacteria add no sugars at all.

To create human-style glycoproteins, some researchers are breeding genetically engineered plants or cattle that might secrete the molecules in their leaves or milk. Others are attempting to humanize insect or bacterial cells or are synthesising the proteins via clever chemistry.

Gerngross is the co-founder of a company called GlycoFi that hopes to capitalize on the yeast. His team has already humanised it even further, he claims, by engineering strains to carry extra enzymes that tweak the sugars into a more final human form.

1. Hamilton, S. R. et al. Production of complex human glycoproteins in yeast. Science, 301, 1244 - 1246 (2003).|Homepage|