The challenge
Making wheat healthier
Barley and oat grains contain high levels of soluble betaglucan which can lower cholesterol reabsorption in the gut leading to healthier blood cholesterol levels and lowering the risk of heart disease. Wheat does not have this beneficial property as the grain has low levels of betaglucan with a slightly different structure making it insoluble.
Cholesterol and high blood pressure are the two main causes of coronary vascular disease CVD (heart disease and strokes) the biggest cause of death in the western world. Approximately one third of US adults have high cholesterol, causing 800,000 deaths per year and costing more than US$300 billion per year in direct medical costs alone in 2011. Of these deaths, 100,000 are preventable with treatment and changes in diet.
Worldwide production of wheat in 2017 was 771 million metric tonnes, five times more than barley and nearly 30 times that of oats - the two other cereals that contain significant amounts of betaglucan.
Our response
Uncovering the secret life of betaglucan
To lower cholesterol reabsorption in the gut, betaglucan needs to be both soluble and viscous and these properties are related to the betaglucan structure. We wished to understand how betaglucans with different structures are synthesised and use this knowledge to make wheat with cholesterol lowering properties.
Betaglucan is made by an enzyme that sits in the membrane at the surface of the plant cell. This enzyme links activated glucose sugars from within the cell and extrudes the growing betaglucan chain through a pore in the membrane into the cell wall surrounding the cell.
In betaglucan the glucose molecules are linked together by a mixture of β1-3 and β1-4 bonds, shown as red and black hexagons respectively in the diagram. The ratio and arrangement of these bonds differs between cereals and this affects the solubility of the betaglucan.
We examined what controls betaglucan structure by expressing the betaglucan synthase gene (also known as CslF6) from each of the different cereals (wheat, barley, Brachypodium (a model plant), oat, rice, maize and sorghum) in the leaves of tobacco, a plant which does not contain any betaglucan.
The results
You’ve got to have the right shaped hole
By examining the structure of betaglucan produced in the tobacco leaf, the cereals could be grouped into two classes; one including oats and the other including wheat. By mixing and matching bits of the CslF6 protein from each of the two groups, we identified the region of the betaglucan synthase that controls the structure.
We discovered that the shape of the membrane pore through which the betaglucan exits the cell controls the polymer structure. In fact it is just a single amino acid difference at the base of the membrane pore which controls the betaglucan structure, making it more or less soluble. We think that this difference in shape changes how the glucan acceptor chain (the end where the next glucose molecule will be added) is presented to the active site altering the frequency of β1-3 and β1-4 bond formation and hence overall structure.
This groundbreaking study was published in Science Advances: Membrane pore architecture of the CslF6 protein controls (1-3,1-4)-β-glucan structure.
First steps to making wheat as healthy as oats
The next steps towards wheat with cholesterol lowering properties are already underway. In a proof of principle experiment, we have taken the oat CslF6 gene and expressed this in the wheat grain showing that we can increase both the amount of betaglucan and change the structure so that it is as soluble as barley betaglucan. We did this in trials using genetically modified plants, a great tool to gain knowledge.
The trial wheat plants were grown in a controlled field trial (approved by the Office of the Gene Technology Regulator) to get enough grain to evaluate the suitability for bread-making and potential health benefits such as lowering the level of cholesterol reabsorption. Nutritional trials with small animals fed white flours milled from wheat grown in the field showed strong metabolic health indicators and positive indications of cholesterol lowering properties compared to control wheat flour.
New wheat lines have also been developed with even higher levels of soluble betaglucan. These lines have more soluble betaglucan than found in some barleys. Larger scale nutritional trials on these lines will be conducted soon. These trial will be conducted with wholemeal flours, which have much higher levels of fibre than white flours and should provide further evidence of the substantial health benefits of these high-fibre wheats.
The next stage of research involves using the knowledge we have gained to develop non-genetically modified high betaglucan wheats using gene editing. This work is done in collaboration with Professor Caixia Gao at the Chinese Academy of Sciences in Beijing. Future work will also be done in the CSIRO Precision Health Future Science Platform.
As wheat is consumed by a large proportion of the population on a daily basis and in much greater amounts than barley or oats, wheat grain with high levels of soluble betaglucan could have high socio-economic impact by bringing heart health benefits to the community.