Biotech Heads For The Factory Floor

First, bioscientists reinvented the drug biz. Now they're designing enzymes for industry

Sometimes the only way to push science forward is to build a paper mill on a table top. That's what researchers at Diversa Corp. (DVSA ) did to test proteins that were custom-designed in their labs in San Diego.

These environmentally friendly molecules could one day replace the toxic chemicals the paper industry uses to turn trees into newsprint, tissue, stationery, and other staples. Ultimately, Diversa CEO Jay M. Short hopes the proteins will help generate a different sort of paper: millions of greenbacks. "Adoption of biology in manufacturing will move fast," he predicts. "It will change industries."

Over the past 30 years, biotech companies have built a $40 billion industry around vats of living cells that produce some of the world's best-selling drugs. Diversa and other companies are betting that biotech can work similar magic for stodgy industries such as paper, textiles, and petrochemicals. The key tools will be new breeds of enzymes -- protein catalysts that speed up chemical reactions in cells. In the future, countless customized varieties could be integrated into many manufacturing processes, making traditional chemical agents more efficient -- or in some cases replacing them altogether.


Chemists have been preaching the gospel of enzymes for decades, but industrial manufacturers have been slow to embrace them. The world consumes only $2 billion a year in such molecules -- and they're used mostly for isolated processes such as stonewashing blue jeans, improving the cleaning power of detergents, and manufacturing vitamin B2. Many other applications have foundered because users didn't want to spend millions of dollars changing their production lines to accommodate pricey enzymes that promised just a few percentage points of cost savings on chemicals and waste disposal. "Yes, enzymes are environmentally desirable. But they have to be economically desirable, too," says Paul Gilman, assistant administrator for research and development at the Environmental Protection Agency.

Biologists are stepping up to answer that call. By employing many of the same technologies used to discover and manufacture new drugs, they're developing enzymatic processes that are cheaper, more efficient, and easier to deploy than the first generation was. The rewards for the inventors and for the manufacturing sector could be significant: McKinsey & Co. estimates that the total value created -- in efficiency gains, enzyme sales, and profits generated by products made using industrial biotech -- could double, to $12 billion a year by 2010.

Several companies hope to dominate. Diversa, on July 15, began selling a custom enzyme for bleaching paper. The company harvested the enzyme from a soil sample near geysers in Russia, and then engineered it to work at a range of temperatures and alkaline levels. Diversa recently launched another enzyme that scours fabrics before they're dyed, which leads to more intense colors in the finished textiles. But other startups are developing similar products. And enzyme giants Novozymes and Genencor International Inc. (GCOR ), are gearing up as well.

Perfecting enzymatic methods is just one of the challenges confronting this growing group of rivals. The players will also have to gain the confidence of traditional manufacturers, many of whom are clinging to processes that are 100 years old or more. More of them might be encouraged to adopt the new technology if Washington offered tax breaks, but no such policies are in sight. "For the bio-economy to evolve, the U.S. government is going to have to give these manufacturers incentives to change," says Jean-Jacques Bienaimé, CEO of Genencor.

Early enzymes mostly failed because they were blunt instruments. The molecules were selected for a function they performed naturally in cells -- but duplicating nature wasn't good enough, the enzyme makers realized. So many of them, including Diversa, are now focused on designing these proteins from the ground up to conform to the exact conditions -- and efficiencies -- manufacturers demand. Some researchers simply tweak existing enzymes, while others are trying a radical approach called directed evolution.

In essence, they are creating entirely new microorganisms that churn out super-enzymes. Using high-speed screening technologies, researchers mix and match DNA from different organisms, looking for just the right combination of catalytic properties. Then they subject each new microbe to varying levels of temperature, acidity, and other conditions. The ultimate goal: to create organisms that can pump out high levels of designer enzymes, which can be dropped right into existing manufacturing processes without requiring companies to overhaul their production lines.

Designer enzymes may be the key to turning niche markets into blockbuster opportunities. Novozymes, for example, has been laboring to improve Resinase, an enzyme that reduces the amount of wood by-products that gunk up the machines of newsprint makers. The enzyme has been in use since the early 1990s, but last year Novozymes reengineered the protein so it works at higher water temperatures than the original version does. "To drop or raise temperatures on thousands of gallons of water each day takes a lot of energy and is just too costly for some paper mills," says Bernie Yemc, an account manager for Novozymes. Such changes could jolt a sleepy market: Less than 10% of papermakers use enzymes today.

Some complex manufacturing processes will demand multiple designer enzymes. That's what DuPont (DD ) scientists realized when they invented Sorona, a soft, static-resistant polymer DuPont markets as an alternative to polyester and nylon. To save money and cut down on toxins, DuPont decided to make Sorona from corn instead of petroleum -- but first it needed a new production process. Working with enzyme-maker Genencor, DuPont scientists transplanted six genes from two different microorganisms into one microbe. It produces four different enzymes that, together, turn affordable corn-derived glucose into propanediol, the key ingredient in Sorona.


DuPont's challenge didn't end there. Researchers also had to tweak the organism's DNA so it would expend most of its energy making propanediol rather than replicating itself. "We sweated blood over this for seven years," says DuPont scientist Scott Nichols. The payoff: On May 26, DuPont announced that it will build its first commercial production plant for Sorona, which will allow the company to mass-produce the material starting in 2006. "Without biotech, this would not have been economically viable," Nichols says.

In fact, the commercial viability of many bio-based products is not yet clear. Cargill Dow LLC uses an enzymatic process to turn corn into an alternative to plastic. Problem is, the material wilts under high heat. Cargill's corn-derived cups were used at the 2002 Winter Olympics in Salt Lake City, but they could only hold cold drinks, admits Dennis McGrew, chief marketing officer for Cargill Dow.

Such risks haven't discouraged Potlatch Corp. (PCH ), a papermaker in Spokane, Wash. It started using an enzyme for bleaching two years ago, and is now saving 10% a year in chemical costs. So Potlatch is thinking of further collaborations that might help it save more on production. "We're going to put up our periscope, look around, and see who's out there," says mill technical assistant Tom Harms. He's likely to spot Diversa, and many others, waving on the horizon.

By Arlene Weintraub in San Diego

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