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Tailor-made sugar coated proteins manufactured in novel E. coli system

The prospect of using bacteria to manufacture complex human proteins for use in therapeutic drugs is a step closer thanks to new research published today in Science.

Researchers from Switzerland and the UK report they have engineered the bacterium Escherichia coli to carry a vital piece of cell machinery that adds sugar molecules to newly synthesized proteins by a process known as glycosylation.

The finding opens up the possibility of producing complex human proteins such as Factor VIII and the hormone erythropoietin, which stimulates the production of red blood cells by stem cells in bone marrow. Both these proteins, which require the addition of sugar molecules to function properly, are currently produced by culturing mammalian cells, which can be a costly and technically difficult process.

The addition of sugars to proteins by glycosylation is crucial in defining their job in the body by helping them fold into a particular three-dimensional shape that determines how they interact with other proteins.

Simple bacterial cells normally do not possess the same type of cellular machinery used for glycosylation in higher organisms like humans. Until now this has restricted the types of human proteins that can be produced in bacteria.

The team of scientists from the Swiss Federal Institute of Technology, Zurich, the London School of Hygiene and Tropical Medicine and Imperial College London have shown that the bacterium Campylobacter jejuni uniquely contains glycosylation machinery similar to the type found in higher organisms. They have developed a technique of transferring this machinery into the E. coli bacterium, which is widely used in the industrial production of proteins.

Professor Anne Dell of Imperial College London said:

"We are only now beginning to understand the vital biological role sugars play in monitoring and guiding the day-to-day lives of the cells in our bodies. This work opens a path for th
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Contact: Judith H Moore
j.h.moore@ic.ac.uk
44-20-7594-6702
Imperial College London
28-Nov-2002


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