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Findings could aid efforts to harness nature for making drugs

hat cause plants to make greater quantities of the enzymes and enzymes that are more productive.

The method pursued by the Purdue researchers was to focus on a gene responsible for producing ferulate 5-hydroxylase.

Altering the composition of nutrients fed to the yeast cultures and controlling the fermentation time caused the gene to be "expressed," producing 45 percent more of the enzyme while doubling the enzyme's activity.

Increasing the quantity and activity of various cytochrome P450 enzymes might enable scientists to use plants and microorganisms like E. coli and baker's yeast to one day commercially produce pharmaceuticals. More progress is needed, however, before it will be practical to use plants and plant enzymes in microorganisms as natural pharmaceutical factories, Morgan said.

"I wouldn't consider this a major breakthrough, but it does represent significant progress in improving the expression of the enzyme," he said. "I think there is certainly room for greater expression of these P450 enzymes."

The same technique could be used to increase the production of other P450 enzymes, Morgan said.

"The plant kingdom contains a large and relatively untapped diversity of P450s that are needed to create thousands of valuable natural products," he said.

In ongoing work, the Purdue researchers also are trying to develop methods for coaxing the enzymes to make drugs not normally produced by plants.

"We are feeding them what's known as substrate analogs, or compounds that are structurally similar to the compound that this enzyme will normally recognize and react with but are somewhat structurally different," Morgan said. "Therefore, if the enzyme recognizes this compound, it will produce a novel product, or a product that's never been synthesized before.

"From a scientific standpoint, we want to better understand precisely how organisms make certain compounds, and from an engineering standpoint,
'"/>

Contact: Emil Venere
venere@purdue.edu
765-494-4709
Purdue University
28-Jan-2004


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