Deciphering the 'language of sugars' to benefit health and industry
Tomato ketchup may have been commonly used in low-budget movies to simulate blood, but the two substances actually have more in common than might first appear. Both are fundamentally affected in the way they behave by the actions of complex sugar molecules. That link may seem technical and obscure, but it points the way to a potentially vast range of benefits for human society - if only science could better understand and harness the capabilities of these molecules.
It was this challenge which formed the focus of PolyModE, a four-year research project set up in 2009 with the support of 6 million euros of European Union (EU) funding.
It is not just ketchup and blood whose properties are dictated by complex sugars. Also known as polysaccharides, these complex sugars are by far the most abundant biomolecules on the planet. Produced biologically in plants, animals and microorganisms, they determine how cells behave in a multitude of ways. Sometimes, their role is structural, giving strength to plant cell walls. Sometimes they store energy. And they carry vital information by which cells ‘communicate’. Human immune systems often recognise pathogens by the sugar structures on their surface.
The sheer diversity of the structures and capabilities displayed by complex sugars, together with the fact that they are natural materials and therefore biodegradable, makes them tremendously valuable to a range of industries. These include food and cosmetics, where they can be used as thickeners or emulsifiers, and the health and pharmaceuticals sectors. Back to that ketchup and blood comparison: one type of polysaccharide is used to achieve the correct viscosity in ketchup, while another helps to prevent blood coagulation in dialysis patients.
The problem is that the polysaccharides with the most useful properties are often produced by only a very few specific organisms, so supply is extremely limited. For PolyModE, therefore, the task was to maximise both the supply of these sugars, and their uses. Since polysaccharides act as the ‘language’ used between cells, the PolyModE team’s primary challenge was to learn that language. This was no small matter. Whereas the language of genes famously makes use of just four ‘letters’, there are more than 20 letters in the language of sugars. Even worse, these can be linked in varying ways - and even with different ‘accents’.
It was clear to the team that the key lay in the machinery used by the cells themselves to ‘read’ and ‘write’ their language – the enzymes. (Hence the name of the project: POLYsaccharide MODifying Enzymes.) If the project could identify, analyse and then produce these enzymes, the enzymes could be used to synthesise the most desirable polysaccharides. As well as boosting production of the polysaccharides that were in limited supply naturally, a further intended benefit was the generation of entirely new polysaccharides with improved properties.
Bringing together biologists, chemists, microbiologists, biochemists, molecular geneticists and biotechnologists from universities, biotech firms and food and pharmaceutical multinationals from around Europe, PolyModE has now identified its first ‘reading’ and ‘writing’ enzymes. These include an enzyme which can be used to modify chitosan, a polysaccharide derived from shrimps and crabs, into a form which carries out specific biological activities. This is now being tested for its ability to protect plants from disease - and it is possible it will also be able to influence wound healing in human tissue.
The consortium has also identified an enzyme which modifies low quality carrageenan - a polysaccharide derived from red algae and with various uses in the food and cosmetics industries - into a novel type of carrageenan never seen before. This is now being commercially evaluated.
“Enzymatically produced designer polysaccharides with defined properties will open up the all-but-untapped potential of complex polysaccharides not only for applications in the food and medical sciences, but also in agriculture, cosmetics and beyond,” says PolyModE’s project co-ordinator, Professor Bruno Moerschbacher of the University of Münster in Germany.
The first commercially available results of the project – the chitosan for plant disease protection – could be on the market within two years, says Professor Moerschbacher.
Project acronym: POLYMODE
Participants: Germany (Coordinator), France, The Netherlands, Bulgaria, Sweden, Denmark