Sugars make proteins more human
the attachment of sugar groups to proteins - a process known as
glycoslation - which could open the door to making a broad range of
human proteins in bacteria, writes Phil Taylor.
The latest discovery, by researchers at the University of Natural Resources and Applied Life Science in Vienna, Austria, goes against conventional wisdom - only now starting to be changed - that only multicellular organisms were capable of modifying proteins by attaching sugars to them.
At present, many large protein-based drugs such as monoclonal antibodies are made in mammalian cells, because it is important that the pattern of sugar side chains on the drug is as human-like as possible. Otherwise, the activity and safety of the drug may be compromised.
The leader of the research team, Prof Paul Messner, told In-Pharmatechnologist.com that while the research is still in its early stages, it is conceivable that in time it could be used to make proteins in bacteria that can currently only be made in mammalian systems.
Their discovery comes from experiments looking at how bacteria protect their proteins in extreme environmental conditions, using thermophilic bacilli that have adapted to survive the relatively high temperatures (50 to 70 degrees C) in sugar beet extraction.
They found that three strains of these bacteria had genes for coping with environmental conditions directly next to one another on the genome. And it turns out these genes are responsible for attaching sugars to proteins to effect a change in their properties for building up a specific protective coat known as the S-layer.
Prof Messner said: "A part of these functions may be mediated by sugars bonded to proteins, which means that this glycosylation may modify the biological function of the proteins for the organism."
Moreover, the scientists have identified the machinery required for glycosylation in these bacteria on a genetic level. They found 15 to 30 genes arranged in a cluster depending upon the strain of bacteria studied, which probably gave an advantage in their competitive natural living space.
The project's next step is to provide greater detail on the function of the genes responsible for linking the sugar residues to proteins.
To do so, they will transcribe the individual genes into their proteins (enzymes and transporters) in vitro and analyse their function in detail.
Carbohydrate engineering
Arguably, a knowledge of this interaction will also form the basis for intelligent utilisation of glycosylation, allowing researchers to apply it to biopharmaceutical development and production.
"The trouble with the methods previously applied for producing glycosylated proteins in bacteria is the fact that they are often glycosylated insufficiently or improperly, which reduces their biological activities," commented Prof Messner. However, modifying the gene sequences will allow us to create bacterial proteins with a tailor-made sugar structure in the future.
