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Human gene may produce blue rose

Roses are red. Violets are blue. Now a gene from a human could turn a rose blue, too. 

Two biochemists researching cancer and Alzheimer's disease drugs at Vanderbilt University made that startling discovery quite by chance — and it could prove to be the grand prize for rose-lovers yearning to grow naturally blue roses. 

Roses occur in many colors in the red-to-yellow end of the spectrum — red blend, mauve, apricot, pink, white and more — but blue ones do not yet exist in nature, according to the American Rose Society. 

Model Aya Kato displays the world's first blue roses at a media preview in Tokyo Wednesday, June 30, 2004. The blue roses, that had been thought impossible to create for years, was developed by Suntory and Australian bio venture FlorigenePty, Ltd., using biotechnology. Blue color pigment extracted from blue flowers was added to roses by recombinant DNA techniques. (AP Photo/Shizuo Kambayashi)

In the world of blooms, blue is a particularly difficult hue to achieve because of the complex genetic and environmental cues that lead to its expression. The blueness seen in flowers like the petunia depend on the synthesis of a pigment called delphinidin, or 3',5'-hydroxylated anthocyanin. But co-pigments such as flavonol or flavones must also be present to prompt a blue shift in the anthocyanin absorption spectrum. And the vacuolar pH must be high to produce a true blue color.

Back in the 1980s, a new breed of horticulturist started to experiment with flower color. Peter Meyer and colleagues at the Max-Planck Institute in Cologne, Germany, were the first to apply genetic modification to flower color.

In 1986, the biotechnology company Florigene was founded in Melbourne, Australia, to pursue the development of a blue rose, carnation and chrysanthemums. The three varieties comprise 50% of the world market in cut flowers. The company isolated two genes necessary for delphinidin production and initiated a program to introduce them into the flowers. So far, Florigene has developed four varieties of transgenic "blue" carnation — but even these appear more mauve than truly blue.

Tim Holton of the Queensland Biotechnology Center in Brisbane, Australia, led the blue rose project at Florigene for 10 years. He explained "It was easier to transform the carnation, in part, because we began with a white flower. The strategy Florigene is using in the rose requires the blue pigments to compete with the natural red pigments. Suitable white roses did not exist."

Holton further clarified, "Three things are needed to produce a blue flower: 100% delphinidin production, flavonol and acyl groups." Insertion of the delphinidin synthesis genes can augment production of the appropriate pigment, but roses lack acyl groups. (Complex acylation pathways are important in producing a blue petunia.) Roses are also acidic. In the alkaline vacuolar environment of the petunia, delphinidin is blue; but in the acidic rose vacuole it is pink. The carnation has a more alkaline vacuolar environment than the rose.

A third gene involved in delphinidin synthesis in the petunia was identified in 1999. The gene encodes a cytochrome b5 enzyme that enhances the formation of 3',5' substituted anthocyanins. Petunias in which the gene had been

Peter Guengerich and his colleague Elizabeth Gillam made their accidental finding as they were studying how drugs are metabolized in the body. They took a gene from a human liver and placed it into bacteria. 

"The bacteria turned blue," said Guengerich, professor of biochemistry and director of the Center in Molecular Toxicology at Vanderbilt. "That was surprising. 

After seeing a flask of bacteria transformed with P450 genes turn blue, Gillam had a "Eureka" moment. "I had previously read about Florigene and immediately thought this presented an alternative" to the existing methods of genetically engineering a blue hue into plant life.

"We knew people have been interested in making a blue rose for years", said Guengerich, "so we thought if we could move these human genes into flowers, we might come up with one." 

Guengerich and Gillam have filed for a patent for their process, but have encountered some thorns in the research. 

"In our initial attempts, the gene didn't know whether to turn the stem or the thorns or the flower blue," Guengerich said. "We've seen some of each." 

Guengerich said it could be a year or more before a blue bloom materializes. 

"I'm working on other things with the drugs," he said. "And, it will take some time to work on the blue showing up in the flowers rather than the stems." 

Sam Jones, chairman of this weekend's Nashville Rose Society Spring Show, was excited by the discovery. 

"It's a goal we've been looking for for a long time. And for it to come about from biochemistry rather than plant breeding is very unique," he said. 

"It should be a very popular rose, because blue is often associated with patriotic themes. You could have red, white and blue bouquets," he said. "And it's novel, as well."




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