One day, commodity chemicals to make pharmaceuticals, agricultural adjuvants, plastics, and transportation fuels will be produced nearly exclusively from plant-derived sugars rather than from fossil-based raw materials.
||FILLING UP Iogen uses this 180,000-L fermentor to produce enzymes for its new technology to convert plant cellulose to ethanol for transportation fuels.
How soon? Proponents of industrial biotechnology believe the needed technologies are at hand and that a biobased world economy is in sight. Industry observers tend to agree with this vision, and they are supportive of industrial biotech. But they caution that the future growth and success of producing commodity chemicals and consumer products through novel bioprocesses will depend on the fate of crude-oil supplies and prices and the quality and availability of feedstock crops.
The hyperbole and the reality surrounding industrial biotech were highlights of the inaugural World Congress on Industrial Biotechnology & Bioprocessing, held April 2123 in Orlando, Fla. This conference, organized by the Biotechnology Industry Organization (BIO), American Chemical Society, and National Agricultural Biotechnology Council, brought together some 500 scientists and business leaders for the first time to share their thoughts on the developing technologies and remaining challenges that are required for moving away from a dependence on petroleum.
Major topics discussed in the technical sessions in Orlando included harnessing microorganisms for chemical and energy production, designing and implementing large-scale biorefineries, social and environmental impacts of biotechnology, and the role of academic research and training to meet future industrial needs.
"Biomaterials will have a greater global economic impact than the agrarian, industrial, and information ages put together," noted Richard W. Oliver, a conference plenary speaker. Oliver is author of several books on biotechnology and business and is the chief executive officer of American Learning Solutions and the American Graduate School of Management. The impact of industrial biotechnology will come much quicker than the impact of past technology advances, he predicted.
"We are entering the growth phase of the greatest and smartest economic boom in the history of the world," Oliver said. "A simple ear of corn will prove to be so smart that it will make a personal computer look rather lame by comparison."
BIO President Carl B. Feldbaum offered a more subdued assessment: "Industrial biotechnology can lead the way toward environmentally sustainable industrial and economic growth. Biotech-based processes can be cleaner and increasingly cost-competitive with conventional environmentally harmful and energy-intensive manufacturing. With industrial output in populous nations such as India and China growing at warp speed, we desperately need new technologies that enable sustainable growth."
Feldbaum also offered a bit of "unsolicited advice" to attendees as they plan the future: Focus on products that make people's lives better. Deal openly and honestly with potential safety or ethical controversies that may be raised by new technologies or products. And reach out to the environmental and agricultural communities as valuable allies.
INDUSTRIAL BIOTECHNOLOGY is considered separate from but complementary to pharmaceutical biotechnology and agricultural biotechnology. Although sugars and oils derived from plants are primarily used thus far to make chemicals, a major effort of industrial biotech is to use the cellulosic parts of plants as the sugar source. Cellulosic biomass includes wood and paper mill residues, urban wood waste, and agricultural plant residues. Dedicated tree farms, corn, or soybeans are expected to be major sources of sugars and oils.
As discussed at the conference, the advantages of these cellulosic materials are that they will one day be less expensive than petroleum, they shouldn't affect food supplies, and chemicals derived from them have an overall lower environmental impact than petrochemicals. The use of genetically modified plants or microorganisms for industrial biotech also doesn't have the social stigma associated with genetically modified foods. In addition, cellulosic biomass is considered "CO2-neutral," since burning it with coal in power plants or using it to create ethanol to use as a fuel doesn't add carbon to the environment beyond what it recently took for the plants to grow.
Industrial biotech currently accounts for about 5% of global chemical sales, primarily through ethanol, pharmaceutical intermediates, citric acid, and amino acids, according to Jens Riese, a conference plenary speaker and a principal with consulting firm McKinsey & Co. This share of sales is expected to reach 10% by 2010, but could go as high as 20%, depending on consumer acceptance and cost, Riese added.
The reason for this quick growth is the development of low-cost enzymes and new recombinant technologies to make the necessary microbes. The economic advantages of developing green technologies will help keep this growth pattern active, he said. Eventually, two-thirds of the global chemical industry could be based on renewable resources.
The most important area of focus for sustainable development is transportation fuels, commented plenary speaker Patrick Moore, a founding member and former director of Greenpeace and now head of Greenspirit, a Canadian environmental consulting group. Moore doesn't believe the "hydrogen economy" will come to pass because the technical challenges are too complex, even though the concept currently has a lot of favor with politicians. "It makes more sense to focus on fuels made from biomass and fuel-efficient vehicles, such as gas-electric hybrids," he said.
Biofuels were the subject of a number of presentations in Orlando. And Canadian industrial and food-grade enzyme producer Iogen announced during the meeting that it had started commercial production at the world's first cellulose ethanol fuel plant.
Cellulose ethanol is made from crop residues such as wheat straw and corn stover--the stalks, leaves, and cobs--rather than cornstarch derived from corn kernels. The process uses "steam explosion" to free the cellulose from hemicellulose and lignin in the raw plant material, allowing cellulase enzymes to more efficiently digest the fibers. In current processing, mechanical treatment and acids are also used to hydrolyze the cellulose. The enzymes convert the cellulose to glucose and hemicellulose to pentoses. The sugars, in turn, can be fermented to ethanol or chemical feedstock compounds.
Iogen obtains about 600 kg of sugar from 1 ton of wheat straw, which in turn produces nearly 85 gal of ethanol, according to Tania Glithero, the company's marketing director. The process also yields about 200 kg of lignin, which is burned to produce electricity. Iogen's Ottawa plant has annual capacity of 260,000 gal, she told C&EN, and the company is set to break ground on a 42 million-gal plant that is expected to be completed in 2007.
THE CELLULOSE ethanol technology was developed by Iogen through a partnership with Petro-Canada and the Royal Dutch/Shell Group. Petro-Canada is using the ethanol to blend with gasoline at its Montreal refinery. The market for cellulose ethanol is expected to grow to $10 billion by 2012, according to Iogen. The Department of Energy expects that ethanol could eventually supply 30% or more of U.S. transportation fuel needs.
Background discussions in Orlando included government policy that could aid industrial biotechnology. For example, the Bush Administration's National Energy Policy has been developed to accommodate legislation such as the Biomass Research & Development Act of 2000 and the Farm Security & Rural Investment Act of 2002. This legislation has prompted a number of federal programs.
Program Manager Todd Werpy of Pacific Northwest National Laboratory described a collaborative project with the National Renewable Energy Laboratory (NREL) to identify the top-tier building-block chemicals as targets for biorefineries. The effort is part of DOE's Biomass Program in the Energy Efficiency & Renewable Energy Office. It's the first of several projects to examine the potential of value-added chemicals derived from biomass using chemical or biological processes, Werpy noted. Future work is expected to examine aromatics, polysaccharides, and oils.
The scientists started with a list of more than 300 potential compounds, Werpy explained. The team narrowed the list through an iterative process that considered the compounds' compatibility with existing petrochemical processing, technical complexity of the syntheses from biomass, known market potential, and other factors. A shortlist of 30 compounds was selected, and from among those compounds the final 12 top-tier compounds were chosen.
The 12 molecules have three to six carbon atoms and multiple functional groups with high potential to be converted to new families of compounds, Werpy said. The compounds are 1,4-diacids (succinic, fumaric, and malic), 2,5-furandicarboxylic acid, 3-hydroxypropionic acid, aspartic acid, glucaric acid, glutamic acid, itaconic acid, levulinic acid, 3-hydroxybutyrolactone, glycerol, sorbitol, and xylitol/arabinitol. A final report, "Top Ten Value-Added Chemicals from Biomass," is expected to be released soon, Werpy noted.
Bioplastics synthesized from some of the compounds on the list are one of the leading production areas of industrial biotech thus far. Although biobased plastics have been around for a century--George Washington Carver and Henry Ford were pioneers in this area--petroleum-based plastics marginalized bioplastics by the 1940s, and they have never recovered.
Cargill Dow uses corn-derived glucose to make lactic acid by a fermentation process for its NatureWorks brand polylactic acid packaging materials and Ingeo brand fibers (C&EN, Dec. 15, 2003, page 17). The company's first world-scale polylactic acid plant, located in Blair, Neb., became operational in 2002 and has annual capacity of 140,000 metric tons. Cargill Dow currently uses corn to produce the sugar to make the polymer, but the company expects to eventually switch over to cellulosic biomass.
DuPont's Sorona 3GT is a copolymer designed to be made from corn-derived 1,3-propanediol and petroleum-derived terephthalic acid. The company currently uses petroleum-derived propanediol to produce some 10,000 metric tons of Sorona per year at a Kinston, N.C., facility. Dupont just announced that it is starting construction on a large-scale propanediol fermentation facility in Loudon, Tenn., in collaboration with carbohydrate processor Tate & Lyle. The plant is expected to begin operating in 2006.
Other bioplastics being developed include poly(hydroxyalkanoates). Procter & Gamble is starting to use its Nodax brand in consumer products. Metabolix, a small technology firm based in Cambridge, Mass., purchased Monsanto's Biopol brand and is working to commercialize it with BASF.
|ENZYME ADVANTAGE Michigan State's Frost overcame a problematic chemical conversion of a carboxylic acid with an enzymatic conversion of an aldehyde to make rocket-fuel precursor 1,2,4-butanetriol.
THE PARTNERSHIPS that have been forged to produce bioplastics--and those in all areas of industrial biotech--are as important as the technical accomplishments, many conference attendees noted. DuPont worked with Genencor International over seven years to produce the engineered microorganism that makes Sorona. Cargill Dow was formed as a 5050 joint venture between Cargill and Dow Chemical to commercially develop NatureWorks based on the route developed by Cargill. Other partnerships discussed in Orlando included enzyme producer Novozymes and NREL, which are working together to reduce costs of enzymes for cellulose processing.
Another useful benefit of industrial biotech is developing new routes to high-value compounds that currently have difficult syntheses. Chemistry professor John W. Frost at Michigan State University outlined three examples in his talk titled "Drugs, Rockets, and Plastics: The Role of Microbial Catalysis."
There are no compounds that can't be made using a microbe, or at least not made more readily by integrating a microbial step in the overall process, Frost said. "What you can make with a microbe leverages what you can make as a chemist."
One advantage of microbial routes over chemical routes is that reactions usually can be carried out at ambient temperatures and pressures, Frost pointed out. This was an important consideration for his "rocket" example: microbial synthesis of 1,2,4-butanetriol from xylose or arabinose. 1,2,4-Butanetriol is a precursor to 1,2,4-butanetriol trinitrate, which is a component of rocket fuel used in single-stage missiles. The butanetriol trinitrate is less shock sensitive, more thermally stable, and less volatile than the propane analog, nitroglycerin, and it could be a suitable replacement if it could be produced practically and economically, he noted.
Commercial synthesis of butanetriol involves sodium borohydride reduction of esterified malic acid, but this stoichiometric route generates tons of by-product borate salts, Frost said. Another route is catalytic hydrogenation of malic acid at high pressure, but this synthesis generates several by-products that are difficult to separate from the butanetriol.
Frost's group was able to prepare D-1,2,4-butanetriol by microbial oxidation of D-xylose to D-xylonic acid, followed by a multistep conversion to D-1,2,4-butanetriol using a different engineered bacterium [J. Am. Chem. Soc., 125, 12998 (2003)]. The researchers also have converted L-arabinoic acid to L-1,2,4-butanetriol by a similar route. The research is part of an effort by the Office of Naval Research to examine the potential of microbial synthesis to prepare energetic materials.
THE NEXT STEP is to get one microbe that can facilitate the conversion of xylose to 1,2,4-butanetriol, Frost said. "The possibility of supplanting Alfred Nobel's formulation of nitroglycerin stabilized on an inert matrix with a new formulation incorporating the much more manageable 1,2,4-butanetriol trinitrate is very exciting," he told C&EN.
"If you just do chemical synthesis, you are kind of limited," Frost said. "When you vary the best you can do with microbial synthesis with the best you can do with chemical catalysis, you are going to be as close as you can be to having unlimited options in converting renewable starting materials to chemical products."
Despite the bubbly exuberance at the Orlando conference, there were some realists in attendance. Kimball Nill, technical issues director at the American Soybean Association (ASA), cautioned that "many of the breezily made assertions" at the meeting regarding the future of industrial biotech don't adequately take into account the needs of farmers or what might be realistic in terms of the use of farmland.
Some speakers asserted that farmers will always be happy to grow, bale, and deliver biomass--that is, switchgrass or corn stover--to burn with coal in power plants or to cellulose ethanol plants for $40 per ton and probably as low as $20 per ton, Nill told C&EN. "But in drought years, the grass would be priced far more per ton as feed for cattle." Another point he made was that transportation of biomass beyond short distances "would quickly cost more Btus [British thermal units] than the biomass fuel would yield." Building an infrastructure to store the biomass is another cost concern, he added.
Iogen's Glithero said farmer contracts should ensure a steady supply of biomass for her company's needs to produce ethanol. She noted that Iogen had thoroughly considered supply, cost, and storage in its marketing plans, but she agreed that over the long term there were no guarantees and that the company didn't yet have a contingency plan if biomass supplies fall short. As the number of ethanol plants continues to grow--some of them owned by farmer cooperatives--competition for the supply of biomass could become intense.
Besides the pricing issue, finding the millions of extra acres of farmland needed to support the burgeoning industrial biotech industry will be a challenge, Nill added. For example, soybean consumption is outstripping supply in most years, he said. Acquiring more land for soybeans has been difficult, so in low-production years prices hit record highs. Although many acres of former farmland lie unused, much of it set aside by government programs, attempts to grow crops on it likely wouldn't be economically feasible.
One possible source of a significant amount of biomass from trees is some 200 million acres of U.S. forests that may be cleaned up under a federal program to prevent fires, according to Greenspirit's Moore. "Trees are the answer," he advocated.
Another point Nill and others brought up throughout the meeting is the willingness of farmers to remove large amounts of plant residues from their fields year after year [Science, 304, 393 (2004)]. Agricultural programs at land-grant universities and state and federal agricultural extension agents have worked for years to educate U.S. farmers about the need to return plant material to the soil through conservation tillage practices to preserve long-term soil structure and health, Nill said.
THE RUSH to use glucose to replace crude oil also may be premature. Although petroleum prices have reached high levels in recent months, petroleum is still a cheaper starting material than biomass. And that may not change for some time.
Some scientists have been predicting for years that world oil reserves have been underestimated. A recent policy paper by Leonardo Maugeri of Italian oil and gas company Eni makes a case for this point of view [Science, 304, 1114 (2004)]. Estimates of proven world oil reserves have been increasing since the 1940s with growing knowledge about specific deposits, advances in technology for recovering the oil, and other factors, Maugeri contends. The best estimates put proven world oil reserves at 1 trillion to 3 trillion barrels, a relative abundance at the current consumption rate of 28 billion bbl per year. Maugeri cautions that "crying wolf" over oil availability has traditionally led to obsessing over national security and has contributed to "oil imperialism" in Western countries.
Despite Maugeri's conclusions, fossil-based resources are finite and are destined to run out. As a DOE report from the late 1990s stated: It is futile to debate when this will happen, but it will happen, and efforts should be made to look for new paradigms to allow gradual conversion to other sources. Conversations that unfolded in Orlando supported that logic and indicated that the attendees have reached a consensus that industrial biotech is an opportunity to design a new industry for environmental performance.