Industrial Biotech Gains Momentum

The ability to "cut-and-paste" genes from one microorganism into another in order to mass-produce enzymes or desired chemical products is a pretty neat trick. In fact, it has been so good for chemical process industries that an entire new biotechnology business sector, that of industrial biotechnology, has emerged.

"Industrial biotechnology magnifies and expands nature's vast genetic database to improve manufacturing processes and to help make new products from renewable feedstocks," notes Brent Erickson, executive vice president for the Industrial & Environmental Section at the Biotechnology Industry Organization (BIO). Erickson has been spreading this message at a number of venues in the past few years.

Industrial biotechnology is the third sister of biotechnology, following on the heels of the now-established health care sector, which includes biopharmaceuticals, and the agricultural sector, which includes genetically modified crops. Although metabolic engineering of microorganisms is the driving technology, chemistry is still the essential ingredient for industrial biotech, and chemical scientists of all stripes and at all degree levels will have plenty of job opportunities in start-up companies created to develop new processes and products or in established companies that adopt new technologies.

A number of industrial biotech products are already widely used. For example, proteases are essential components of laundry detergents where they aid removal of proteins in food or grass stains, xylanase enzymes are replacing chlorine in pulp and paper bleaching to reduce chlorine use and energy consumption, and amylases are used to convert cornstarch into glucose which in turn is fermented by yeasts or bacteria to make ethanol.

Other industrial biotech products include bioplastics, semisynthetic drugs, modified vegetable oils for processed foods, biodiesel, biosurfactants, and commodity chemical feedstocks. As an example of the latter, Erickson points out that agribusiness giant Cargill is developing 3-hydroxypropionic acid derived from glucose rather than petroleum as a platform chemical to make acrylic acid, 1,3-propanediol, and other intermediates.

"Industrial biotech is already taking off and will be one of the key innovation drivers over the next 10 years in chemicals," Erickson says. There's still a "technology gap" where biotech tools are available but companies don't know about them or are not familiar enough with biology to adopt them, Erickson observes. But that gap is expected to close rapidly. By 2010, about 20% of the global chemical market will involve industrial biotech production, according to a study by consulting firm McKinsey & Co.

The big news of the moment is the development of cellulases to convert cellulose to sugars, which are then converted into ethanol for transportation fuels. Federal programs authorized by the Energy Policy Act of 2005 are designed to support R&D for biomass ethanol production, support private investment in biorefinery construction to make ethanol and other commodity chemicals, and provide monetary incentives for quick adoption of cellulosic ethanol for fuels. President George W. Bush, in this year's State of the Union Address, provided a jolt of momentum to the industrial biotech industry when he voiced support for cellulosic ethanol development to help ease U.S. dependence on imported crude oil.

The new energy law includes a federal renewable fuels standard that requires 7.5 billion gal per year of ethanol be blended with gasoline by 2012. Currently, about 12 billion gal of ethanol is produced worldwide and about 4 billion gal in the U.S., nearly all of it made from cornstarch. Overall, the global bioethanol market is expected to grow to nearly 30 billion gal annually by 2020, according to the Renewable Fuels Association. This increase coincides with an expected jump in the enzymes market from about $100 million to nearly $1.1 billion per year, according to company estimates.

The hot spots for jobs resulting from that growth likely will be at small to mid-sized companies as they develop and begin commercial production of enzyme-mediated products. Many of these companies are or will be located in farming regions to be near supplies of agricultural feedstocks.

And because of federal R&D support, many job opportunities related to industrial biotech are at national laboratories. The Department of Energy's Genomes to Life Roadmap has several programs focused on using genomics for cleaner energy production, environmental remediation, and carbon sequestration (C&EN, Dec. 12, 2005, page 39). Other DOE programs focus on developing biorefinery processes to produce fuels and commodity chemicals. Among these are the National Renewable Energy Laboratory (NREL) and the Energy Efficiency & Renewable Energy Office.

Danish firms Novozymes and Danisco's Genencor International division currently dominate the commercial enzymes field. These companies garner about 44% and 18%, respectively, of the enzymes market, notes Jerry Allen, employment manager of Novozymes North America, based in Franklinton, N.C. DSM and BASF each have roughly a 5% share, with the remainder of the market made up of a mix of companies, he says. Genencor was named "the Best Place to Work in America for 2005" for its human resource practices that contribute to attracting and retaining its workforce (C&EN, Oct. 3, 2005, page 67).

Novozymes has just over 400 employees in North America and more than 4,000 employees worldwide, Allen notes. The company has been adding more than 20 positions per year recently, as well as offering a few postdoctoral positions. These positions are a mix of research and "customer solution" tech support jobs at different degree levels but also include some production jobs.

As for recruiting, Novozymes doesn't accept unsolicited résumés but instead focuses on employee referrals and networking at scientific and trade show meetings "to identify talent." The company also announces some jobs on websites, such as Monster and HotJobs.

Companies that work with enzymes tend to focus on enzyme development and production or on commercial product development and production, but usually not both. Novozymes and Genencor, for example, focus on developing enzymes for clients with specific needs for their technology. The companies also look for partners to help further develop enzymes for new applications, particularly for industries that currently don't use them, Allen says.

In one example of their activities, Novozymes and Genencor have worked on separate R&D projects with NREL to improve cellulases for bioethanol production (C&EN, Feb. 20, page 24). A technical hurdle for cellulosic ethanol had been the high costs of the enzymes. But the extra development work has brought about a significant reduction in the enzyme cost of ethanol production using corn stover, in Novozymes' case from more than $5.00 per gal to between 10 and 18 cents per gal.

Companies like BASF, DSM, and Degussa develop biocatalysts internally for their own manufacturing processes, but some of them also make their expertise available to the industry by offering customer services in biocatalysis screening, optimization, scale-up, and production (C&EN, Feb. 20, page 6). As an example of these companies' expected growth, DSM is in the process of hiring for 200 new science positions to move further into industrial biotech, according to BIO's Erickson.

Beyond the major enzyme players, there's a range of smaller companies that are anticipating continued growth and job opportunities. One of these is Canadian enzyme and bioethanol producer Iogen.

Iogen strives to link enzyme development and product development together, and "we're one of the few companies to take that full approach," comments Brian Foody, the company's president and chief executive officer. Iogen's basic strategy is to develop and manufacture enzymes to process natural fibers for pulp and paper, textiles, and animal feed industries, he notes. But the company also is moving forward with industrial processing.

In 2004, Iogen became the first company to produce large quantities of cellulosic ethanol, about 1 million gal per year from wheat straw, at a demonstration plant in Ottawa. Iogen has plans to begin construction in 2007, either in the U.S. or in Canada, on a commercial-scale plant that will produce 40 million gal per year of cellulosic ethanol. Iogen also has partnered with Volkswagen and Royal Dutch/Shell to explore cellulosic ethanol production in Germany.

Iogen currently employs 180 people who work on enzyme development and manufacturing and on cellulosic ethanol production, Foody says. The workforce includes chemical, mechanical, and other process engineers (Foody himself is a mechanical engineer), as well as biochemists, molecular biologists, and protein chemists. It's too early to project how many new employees the company will be hiring as the cellulosic ethanol market heats up and other opportunities arise, Foody adds, "but Iogen is certainly expected to grow."

Dyadic International, headquartered in Jupiter, Fla., and with subsidiaries in Poland, the Netherlands, and China, is another enzyme producer that is working toward developing its own applications.

"We have spent the past 14 years developing and commercializing cellulases, xylanases, and other enzymes that have applicability to pulp and paper, animal feed, food, textile, starch-based ethanol, and the emerging cellulosic ethanol industry," notes Mark Emalfarb, Dyadic's founder, president, and CEO.

Dyadic sells nearly 50 liquid and dry enzyme products to customers around the world, Emalfarb says. The company also offers discovery services for biotech companies, as well as manufacturing services with fermenter capacities up to 150,000 L. The company's biosciences unit is in the early stages of developing therapeutic proteins for biomedical applications.

The company was created in 1979 as an extension of a family-owned landscaping business to provide pumice stones for the denim industry to make stonewashed jeans, Emalfarb explains. During the 1980s, the industry moved toward using enzymes rather than pumice, in part to discontinue open pit mining and reduce environmental impact. Because Dyadic was the leading pumice supplier, it naturally started supplying enzymes as well. The company originally used enzymes produced by Novozymes and Genencor, but by the early 1990s, Dyadic began to make its own.

Dyadic uses a number of proprietary fungal strains to produce its products, but the principal focus is on its patented C1 protein-expression system, which is based on a genetically modified Chrysosporium lucknowense, or C1, soil fungus. The company has sequenced the C1 genome, which has 10,000 to 12,000 genes, and developed the C1 Fungal High-Throughput Robotic Screening System to identify genes that produce proteins of interest. Dyadic's C1 Hyperproducing Protein Expression system, based on recombinant DNA techniques, is then used to increase the production of the proteins. The company also carries out commercial-scale production of the proteins by using optimized fermentation with the C1 fungus as the host organism.

Use of a single organism to carry out the full range of steps from discovery to production is unique to the industry and provides Dyadic with an advantage, Emalfarb points out. Other enzyme producers have to use two or more microorganisms for the multiple stages of the process, he notes.

The company currently has 100 employees worldwide, and another 100 people are employed under contract R&D and manufacturing agreements. The company added 13 new employees this past year, and Emalfarb expects Dyadic to keep growing. In fact, on March 21 the company announced its latest hire: Novozymes cofounder and president, Glenn E. Nedwin, is joining Dyadic as chief scientific officer and president of the biosciences business.

"We anticipate hiring protein chemists, enzymologists, and molecular biologists who can identify new applications for enzymes and proteins and help broaden the capabilities of C1 by mining the genomic data," Emalfarb says. He also expects to hire a range of support staff, including business-development specialists and sales personnel "who possess the necessary skills for helping us to bring new products to the market more reliably and more efficiently."

One of the greatest areas for growth will be for Dyadic scientists to collaborate with academic and industrial researchers to use the C1 expression system to study newly discovered genes that encode for potentially commercially useful enzymes, Emalfarb adds.

"People with ideas should come and work with enzyme companies or let us do the work for them," Emalfarb says. "We are at the beginning of an incredible journey, some purposes we know and some we don't, but we encourage people to come to us to find out more."