Get ready for a sugar rush

By Graeme O'Neill
Wednesday, 27 April, 2005


In 2000, a research team led by University of Queensland molecular geneticist Prof Robert Birch first inserted a gene from the plant-dwelling bacterium Pantoea dispersa into sugarcane cells, aiming to create plants that would synthesise isomaltulose, instead of sucrose.

P. dispersa lives on the surface of plants including sugarcane. Its sucrose isomerase (SI) gene codes for an enzyme that 'flips' the sucrose molecule into a different configuration, or isomer, without changing its constituent atoms or molecular weight.

Isomaltulose is a natural sugar built from the same glucose and fructose sub-units as sucrose. It tastes just like sucrose, but because of superior health attributes as a sweetening agent in confectionery and foods, it is worth 10 times more. Birch's objective was to develop a profitable new form of a familiar crop to boost the incomes of beleaguered growers.

The team was also hoping the SI transgene might produce a modest increase in overall sugar yield - something that has challenged conventional breeding for decades. Preliminary analyses of SI -- expressing sugarcane plants grown in containment greenhouse conditions indicate that the new approach succeeded spectacularly, on both counts. The transgenic plants not only synthesised isomaltulose, some produced it at double the amount they had previously yielded as sucrose.

A further check revealed that some of the transgenic plants were producing isomaltulose with no apparent reduction in sucrose levels. Then the research team found several lines that were producing little or no detectable isomaltulose, but twice the normal level of sucrose.

If those yields are reproducible under field conditions, Birch says, it would be an "an amazing and exciting scientific discovery, and a breakthrough for Australian industry".

More work will certainly be needed, for example to tailor expression patterns for optimal commercial performance. But the approach has the potential to secure the Australian sugar industry's future. "A 20 to 50 per cent improvement in sugar yield, in one step would make the difference between non-viability and a competitive, profitable, sustainable sugar industry," he says.

The sweet proof should be available by the end of this year. At the beginning of the year, the Office of the Gene Technology Regulator approved Birch's application to test the GM sugarcane varieties outside the glasshouse, and they will be planted out in contained field trials this month.

Self-contained

Spread of introduced genes is not really an issue with GM cane. The crop is propagated by stem cuttings, and does not survive well without human assistance. It rarely produces fertile flowers or seeds in commercial fields, and it does not cross-pollinate with any other crop or native plant. Special conditions and skilled breeders are needed to make crosses in sugarcane breeding programs.

Isomaltulose is also a good pilot example of possibilities for a value-added sugarcane industry. The high price of isomalultose reflects its undersupply in world markets, and the high capital and operating costs of existing production methods. Currently, food-grade sucrose is pumped into giant tower fermenters containing SI-expressing bacteria immobilised on tiny beads. The isomaltulose collects at the base of the towers and is drawn off.

Installing the isomaltulose synthesis pathway directly into sugarcane can be a win-win outcome, with higher profit for growers producing a more valuable sugar, opportunities for Australian processors to add further value through approaches such as blends that combine the useful properties of several sugars, and reduced costs making the benefits of isomaltulose available to many more consumers.

The preliminary results have staggering implications -- and they are not confined to the sugar industry.

A 20 to 50 per cent yield increase would transform the economics of ethanol production, giving Australia a renewable source of liquid fuel at a price competitive with petroleum. Other Queensland researchers are developing GM cane varieties that will synthesise precursor compounds for a wide variety of biodegradable biopolymers, that could replace most of the plastics currently made from petroleum.

Isomaltulose is a nutraceutical -- a plant-derived nutrient with significant benefits for human health. Like sucrose, it is a natural way to enhance flavour and preserve other foods. But Birch says isomaltulose has the advantage that it is not used by the oral bacteria that cause dental cavities, and humans digest it more slowly, which can help reduce the risk of obesity and type 2 diabetes.

While the scientific breakthrough came in sugarcane, the technology may have benefits right across agriculture.

Birch points out that all plants synthesise sucrose. It's the basic currency for all biochemical transactions in all plants, not just sugarcane. All complex plant carbohydrates like starch and cellulose, and other molecules like proteins and lipids, derive ultimately from sucrose, the primary product of photosynthesis.

"For vegetable crops, like peas, corn, and carrots, sweetness is a really important character," Birch says. "Total dissolved sugar content is also important in fruit crops, like grapes and tomatoes.

"Concentrating sugars by getting rid of excess water is expensive. You want to produce fruits with a higher level of total dissolved solids, mainly dissolved sugars - the intense flavour of sundried tomatoes is due to their high sugar content. It's a very important commercial attribute. "The potential of the two technologies together is very exciting - acariogenic sugars, and higher sugar content in fruits and vegetables." The SI gene might increase sugar synthesis, and thereby, other major nutrients, in virtually any other cultivated plant - fruit, vegetable, cereal, root, oilseed, fibre or timber crops. It could be a platform technology for increasing yields of carbohydrate, protein or lipid products in these traditional crops. Birch believes it is hard to overstate the importance of such an advance.

Scientists are battling on multiple fronts to double world food production and accomplish the shift to renewable energy and biomaterials, allowing the preservation of as much wilderness and biodiversity as possible.

Extending the technology to boost yields in other major crops is the next step. "That is a huge R&D challenge, and we are keen to bring together the support and collaborations to get it underway," Birch says. "But our first priority is to help capture the value of the technology for the Australian sugar industry, which initiated the research.

"The investment risk in the early research was carried by UQ, the Australian Research Council, The Sugar Research and Develpoment Corporation, and CSR. We all want to ensure that the benefits flow to the industry as soon as possible."

The University of Queensland has patented the technology, and CSR, which has been a major partner in its development, has first option to exploit it commercially in sugar crops.

"We are collaborating to accelerate the laboratory and field testing needed to provide solid scientific information for independent regulatory evaluation, before the technology can be applied commercially" Birch says. "We need to know how the high-sucrose or high isomaltulose lines perform in the field, whether they will be more attractive to cane pests like mealy bugs and aphids, and whether we have to change cultivation systems to get the best out of them. Remember, we've spent 100 years optimising our systems for current cane varieties. "Several things need to happen in parallel before any commercial release. There is absolute commitment by the Australian sugar industry to ensuring human and environmental safety. "Sucrose and isomaltulose are long-established foods, but separate regulatory approval from FSANZ (Food Standards Australia-New Zealand) will be required to use the sugars from the GM cane varieties as foods.

"We are working to insert the SI gene into a range of genotypes, to avoid the risks of monoculture, then we will need to step up the scale of the field trials, and propagate varieties for commercial release.

"It's difficult to imagine us getting this technology into production before 2010. We're very much in the research phase, and the industry is not going to jump into any new technology until it is sure customers are comfortable with it, and the benefits outweigh any additional costs."

In addition to transforming crops, Birch believes the technology will provide new options to farmers. It could allow farmers to produce twice as much sugar or isomaltulose from the same area of land -- or maintain current levels of production from only half the current area.

"It could allow the industry to pull back from marginal land," he says. "In the end, higher yields from our agricultural land are a key to both profitability and sustainbilty."

A healthier sugar

Isomaltulose is a perfect structural isomer of sucrose, with the same molecular weight and calorific content. However, Dr Robert Birch says it has different chemical properties that could provide substantial health benefits when it becomes more widely used in the food industry.

The sugarcane bacterium Pantoea dispersa, source of the sucrose isomerase gene that Birch used to engineer sugarcane, employs the enzyme to convert sucrose into isomaltulose. P. dispersa is uncommon among bacteria in its ability to use both isomaltulose and sucrose as energy sources. Some oral bacteria metabolise sucrose to produce plaque and acids that cause dental cavities, but they cannot metabolise isomaltulose.

As an acariogenic sugar, isomaltulose currently used as the precursor to a low-calorie sweetener called Isomalt in many 'sugar-free' sweets. Birch says isomaltulose can deliver other health benefits as a nutritional sweetener. Eating sugary foods results in a rapid and pronounced 'spike' in glucose levels in the bloodstream, as an invertase enzyme in saliva cleaves sucrose into its constituent fructose and glucose molecules.

Glucose is rapidly absorbed into the bloodstream, where it induces a accompanying insulin spike, that rapidly lowers blood glucose levels. "A meal or a snack high in sugar is followed by a blood glucose spike which is unhealthy for diabetics" Birch says. "Some people, like Prof Jenny Brand-Miller, believe that low glycaemic index (GI) foods have health advantages because they don't give those sharp glucose and insulin spikes -- they produce a much more gradual change."

Isomaltulose avoids glucose-insulin spiking, making people less likely to seek a snack after a meal to assuage their renewed feelings of hunger. "For these reasons, isomaltulose is attractive as a functional food in the health food market," Birch says. "It's currently only a small market, because of the price differential. If we could produce isomaltulose at lower cost, we could develop a larger market because more people could afford the benefits."

Running on ethanol fuel

High-sucrose GM sugarcane could make ethanol more economically attractive as a renewable fuel, according to ethanol expert Prof Peter Rogers, professor of biotechnology at the University of NSW.

Rogers says the cost of the sucrose used to ferment ethanol currently accounts for around half of the $0.50 to $0.60 base cost of producing a litre of ethanol. Halving the cost of sucrose would thus reduce the base cost of ethanol to a level more competitive with petrol.

According to Rogers' figures, when crude oil prices were between US$30 to $40 a barrel, the base cost of producing a litre of petrol was between $0.30 and $0.35. The current record crude oil price of US$55/bbl has lifted petrol prices 25 to 30 per cent. If this continues, halving the cost of sucrose would reduce the base cost of a ethanol to a level competitive with petrol.

Currently, ethanol is blended with petrol at a rate not exceeding 10 per cent, but this concentration could be considerably increased by retuning car engines and changing fuel lines -- Brazil had gone as high as 85 per cent ethanol (E85).

"The real problem is getting the car industry and the oil industry to change," Rogers says. "There has been a massive campaign in Australia to undermine the ethanol industry, but it has been a different story in Brazil, the US and some European countries."

Rogers says public acceptance of GM sugarcane varieties in the face of opposition from anti-GM activists is another problem. He says ethanol also attracts a lower federal tax than petrol, and the government excise could be further reduced to encourage a move to biomass fuel.

The University of Queensland's Robert Birch says the chemical structure of isomaltulose makes it a more attractive proposition than sucrose as a feedstock for manufacturing biodegradable plastics, detergents, solvents, and liquid crystals used in computer screens and other electronic devices.

"As the shift to sustainability increases, new markets will open up."

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