“Reducing America’s dependence on foreign oil requires the efforts of our brightest scientists, our best companies, and strategic investments in biofuels research,” said Vilsack. “Working with private industry and our government partners, we are developing new energy sources from renewable, homegrown next-generation feedstocks. By developing and commercializing advanced biofuels, we will create jobs, provide consumers with new options to fuel their vehicles, and reduce our dependence on foreign oil.”

Agrivida is developing methods to reduce the cost of converting biofuel feedstocks into sugar, focusing on sorghum, corn stover, and switchgrass. The Department of Energy and USDA have helped fund research in this effort through the Biomass Research and Development Initiative. Earlier this month, Secretary Vilsack announced a total of $41 million in grants through the program to fund an additional seven research and development projects throughout the country that will help increase the availability of renewable fuels and biobased products.

USDA also recently announced that the Rural Energy for America Program (REAP) will support flexible fuel pumps, (sometimes referred to as “blender pumps”). This is expected to encourage fuel station owners to invest the capital necessary to give American motorists the option of selecting the blend of renewable fuel that meets their needs. The Obama administration has set a goal of installing 10,000 flexible fuel pumps nationwide within 5 years.

USDA has awarded a total of $6.3 million through the REAP program to fund approximately 60 renewable energy projects in Massachusetts. These include biodigesters, photovoltaic systems, greenhouse thermal curtains, and wind energy projects.

#

USDA is an equal opportunity provider, employer and lender. To file a complaint of discrimination, write: USDA, Director, Office of Civil Rights, 1400 Independence Ave., S.W., Washington, D.C. 20250-9410 or call (800) 795-3272 (voice), or (202) 720-6382 (TDD). ]]> http://inctank.com/press/2011/item/415/feed/ 0 http://inctank.com/press/2011/item/405/ http://inctank.com/press/2011/item/405/#comments Tue, 01 Mar 2011 16:00:55 +0000 jackson http://inctank.com/?p=405 Agrivida scientists plan to be at an event this week supported by the U.S. Department of Energy in the Washington, DC, area, where the startup will show industry leaders its way of providing cheap sugar for making cellulosic biofuels and chemicals.

The Medford, MA-based firm has been on somewhat of a roll as of late. In December, the company announced a collaboration with the Swiss agribusiness giant Syngenta. Agrivida also gained attention in July when it showed that its engineered crops could greatly boost the efficiency of the process of extracting sugars from the crops for biofuel production.

Michael Raab, the firm’s president and an inventor of its technology, says that a big focus for his firm nowadays is to find partners among cellulosic biofuels processors that can help his small company commercialize its technology. Raab’s firm is offering the producers a potential way to significantly reduce the costs of an expensive step in making cellulosic ethanol—the sugar production process. This is the step where the cellulosic biomass gets exposed to pricey chemicals and enzymes and high temperatures to extract sugars from the feedstock that can be fermented into ethanol or other fuels and chemicals.

Commercial cellulosic ethanol doesn’t really exist yet, but companies such as Mascoma of Lebanon, NH, and Qteros in Marlborough, MA, have recently revealed deals to help them advance their processes for making such fuel in larger batches.

While part of the promise of cellulosic processing is the ability to make a variety of products from sources such as grass and plant waste, it’s tough to get the sugar out of these sources compared with traditional feedstocks like corn kernels and sugarcane. Raab says that the enzymes used in the process for plant feedstocks such as grass or corn stalks can add 50 cents per gallon to the cost of ethanol. That is where Agrivida’s technology comes in.

The company develops crops with cell walls that contain inactive versions of the enzymes that are normally added during the process. The company has engineered the enzymes so that they are only activated at certain temperatures and acidity levels during processing. Without this switch capability, Raab explains, the enzymes would cause the crops to wilt before they are harvested.

“We think it’s really going to be huge,” Raab says. “It’s because the competitive pretreatments and use of additional enzymes is way too expensive.”

Genetically engineering crops is nothing new. Seed producers have been working for years on modifying crops to increase harvest yields, extend the growing season, and prevent rotting. Among the major players in the seed game are DuPont, Monsanto, and Syngenta. Raab says that his startup wants to work with these firms to get its traits into seeds that are grown to produce feedstocks for cellulosic ethanol. Of course, the company has already made some progress with Syngenta in terms of gaining access to some of the large firm’s technology and having company as a shareholder.

Agrivida doesn’t want to invest in huge infrastructure to make and sell its own fuel. Instead, it wants to generate revenue from both royalties on sales of seeds that carry its trait for energy crops, as well as earning a cut of the money that cellulosic ethanol processors make from fuel they produce using the firm’s modified crops, Raab explains. Given the time he expects it to take to gain regulatory approvals and validation for the firm’s technology, it might be years before the company starts to make significant money on its modified crops.

To hear Raab tell it, there’s very little chance that cellulosic ethanol can reach the U.S. government’s annual production volume requirements without a technology that reduces the expense of enzymes to break down the crops in the pretreatment process. Today, the government regulates those requirements and sets the amount of ethanol that can be added to gasoline used in automobiles, for example.

The current standard updated in 2007 calls for about 1 billion gallons of cellulosic ethanol to be produced in 2013. The volume should increase to 16 billion gallons by 2022, according to the Environmental Protection Agency. Considering that almost no cellulosic ethanol is being produced commercially today, these requirements call for big jumps in productivity among cellulosic ethanol makers in the coming years.

Michael Raab, president and co-founder of Agrivida

Looking back, Raab and fellow Agrivida co-founder Jeremy Johnson have come a long way since they started the firm while still grad students at MIT in 2003. Johnson is vice president of the startup, which now has about 40 employees. The group raised its first round of venture capital in 2007, bringing in an undisclosed amount of financing from the major VC firm Kleiner Perkins Caufield & Byers and PrairieGold Venture Partners, according to Raab. The startup later closed a second-round financing in 2009 and expanded its roster of investors. Government grants have provided the firm an additional $7.5 million to support its research.

Agrivida is expected to share the spotlight with other firms that are inventing new ways to improve the energy supply for the U.S. this week at the ARPA-E Energy Innovation Summit. In July, the firm revealed that its corn crop that contained the cellulose-degrading enzymes converted more than 65 percent of cellulose into sugar compared with 30 percent for non-modified crops in lab experiments.

Now the company hopes to gain partnerships with cellulosic biofuels processors that can help the firm demonstrate those productivity gains with other types of crops at larger scales.

“We’re developing these relationships now, and have only started that process in the last few months,” Raab says. “We have waited to do this until we had initial materials that we could share with other groups.”

Ryan McBride is Xconomy’s correspondent. You can reach him at rmcbride@xconomy.com, or follow him on Twitter at http://twitter.com/Ryan_McBride.

Agrivida will bolster its existing technology portfolio, including its proprietary intein trait platform, with technology licensed from Syngenta that will be used to develop new traits for multiple crops, including corn, sorghum, switchgrass and miscanthus.  Agrivida’s traits will make next-generation bioproducts more affordable by significantly decreasing biomass processing costs associated with non-food agricultural residues and dedicated biomass crops.

Announcing the collaboration, Mr. Mark Wong, Agrivida’s Chief Executive Officer, said “Agrivida is excited to be able to accelerate our product development through our relationship with Syngenta Ventures, the venture capital arm of Syngenta, one of the world’s leading agribusiness companies.  The combination of Agrivida’s proprietary intein platform with Syngenta’s technology will allow us to provide an integrated solution for feedstock and enzyme delivery to a wide range of industrial customers.  Technologies developed through our collaboration will provide growers, processors, seed partners, and all members of the value chain with crops that enable cost-effective products from cellulosic biomass, and in turn helps to transform this emerging industry.”

Agrivida’s deal with Syngenta is the latest in a number of recent successes for the company.  In July, Agrivida announced breakthroughs in its development of sugar production from enzyme expressing crops at the annual BIO industry conference, which followed recent awards from the U.S. Department of Agriculture (USDA) and Advanced Research Projects Agency-Energy (ARPA-E) to further develop its proprietary technology platforms in sorghum and switchgrass.”

Agrivida, Inc., headquartered in Medford, MA, is the commercial leader in developing improved crops for production of biofuels and bioproducts from non-food agricultural residues and dedicated biomass crops. The company has entered into research and development agreements with the U.S. Department of Energy (“DOE”), the U.S. Department of Agriculture, ARPA-E, and other corporations. The company received the ‘DOE’s 2008 “Energy Innovator Award.” With expertise in protein engineering, molecular biology, plant biotechnology, agronomy, and chemical engineering, Agrivida is leading the industry in the development of innovative, sustainable crops and processes to meet energy needs and protect the environment.

To learn more about Agrivida, Inc., as well as to review other recent news releases, please visit www.agrivida.com.

SOURCE Agrivida, Inc.

Majumdar let his enthusiasm show as he described this project at the Reuters Global Climate and Alternative Energy Summit on Thursday. He was talking about a project in its early stages at Massachusetts-based Agrivida.

“If you look at biofuels, cellulosic biofuels  …  you take agricultural waste, you separate out … the cellulose, then you throw a bunch of enzymes at them. And these enzymes are there in the cow’s gut, or termites, that break down this long chain polymer, this cellulose, into small bits and pieces called sugar molecules. And then you take those sugar molecules and feed them into another bug and then you produce gasoline,” he said.

The costly part of this process, Majumdar said, is growing these enzymes in a bio-reactor instead of in a cow.

“What this company’s doing is a very interesting idea. They take the gene sequences that produce enzymes and put them in the plant itself, so when the plant grows, it produces the enzymes free of cost.” But isn’t there a risk that the plants wouldn’t grow, since they would carry enzymes that would make the plants self-digesting? One possible solution is what this start-up company is trying: make the enzymes inactive, and activate them later by changing temperature, humidity or acidity.

“It’s supposed to chew itself from the inside,” Majumdar said, with evident delight. “And I call this ‘putting the cow inside the plant.’ It’s an amazing idea. Now I don’t know whether it’s going to work, but if it does, you essentially eliminated the cost of those enzymes, which is the really expensive part, and you create a more competitive pathway for biofuels than what is traditionally being done.”

For more from the Reuters Global Climate and Alternative Energy Summit, click here.

Deborah Zabarenko Reuters Environment Forum

Ligon Discovery has its first large pharmaceutical partner, a big deal for any biotech but especially for a company that spun out of an academic lab just 16 months ago. Cambridge, MA-based Ligon is announcing today it has inked a deal with Germany-based drugmaker Bayer Schering Pharma. The deal calls for Ligon to use drug-screening technology to discover potential treatments on behalf of Bayer Schering.

Both companies are keeping the exact terms of the deal under wraps, and no details about the types of diseases that Bayer Schering is targeting in this partnership were disclosed. Christian Bailey, who took over as Ligon’s CEO in June, said that his company is getting both upfront cash and additional payments based on Bayer Schering reaching certain drug-development goals. Bayer Schering is a pharmaceutical research unit of Bayer HealthCare.

The deal lends some credence to Ligon’s claims about the potential advantages of its drug-discovery system, which uses proprietary technology originally from Harvard University to conquer the problem of drugging tricky disease targets. The firm has one previous partnership with a fellow biotech startup, Plymouth, MI-based Lycera, to apply its screening technology to discover potential drugs for autoimmune diseases, which are the main focus at Lycera. But Bayer Schering is the first major drugmaker to form a collaboration with Ligon, meaning that the young firm’s technology passed muster with people who have extensive experience in drug research, Bailey says.

Ligon’s technology might enable its partners to succeed where previous drug-screening methods have fallen short. For example, advances in biological research such as high-speed gene sequencing have led to new discoveries into the inner workings of diseases such as cancer, particularly disease proteins and pathways of disease progression. To hear Ligon’s Bailey tell it, the lengthy and cumbersome process of developing tests to identify drugs against these new disease targets has held back the discovery of potential treatments.

“The challenge is that a lot of the new targets that have been discovered in disease pathways are much more complex than the ones we were finding 10 years ago,” Bailey said.

Here’s how the Ligon method is supposed to work: The firm’s technology involves a proprietary chemistry that quickly links libraries of drug compounds onto glass slides. Those slides are then used to screen the compounds against elusive disease targets to find potential hits. This differs substantially from previous discovery methods that worked the opposite way, building the assays around a thorough understanding of the biological disease targets’ functions, and then running tests to see which drug compounds could alter its function and qualify as a potential treatment lead. But the nuanced disease targets that many drug companies are now toiling with make building assays around them tricky.

“There are targets like chromatin regulators that, to design a target-based screen for them, you would need to understand the multifaceted functions of the target in order to be confident that the screen had any meaning,” Bailey said. “By turning the whole screening paradigm upside down, the Ligon technology allows you to do a target-based screen against that [disease target] without having a complete understanding of its function.”

While Ligon seeks collaborations with partners like Bayer as part of its commercial strategy, the company is primarily focused on applying its drug-screening technology to discover its own treatments for cancer, coagulation disorders, and bacterial infections. Yet its partnerships provide invaluable revenue to the startup as it travels down the long and expensive road to developing drugs. So far, the company has raised $1 million from Cambridge-based IncTank Ventures, where Bailey is a partner, and the CEO wants to land partnerships like the one with Bayer to limit the amount of venture capital the firm will need. (In fact, Bailey led IncTank’s initial investment in Ligon last year before he took the chief executive post in June from the founding CEO, Patrick Kleyn, who has stayed on as the firm’s president and chief scientist.)

In May, I interviewed Kleyn about the some of Ligon’s positive reviews from pharma executives and how it spun out of standout chemist Stuart Schreiber’s lab at Harvard. With this new Bayer Schering deal, the startup has justified some of that attention it got in its early days.

Ryan McBride is Xconomy’s correspondent. You can reach him at rmcbride@xconomy.com, or follow him on Twitter at http://twitter.com/Ryan_McBride.

AgaMatrix Inc., a Salem, N.H.-based maker of blood glucose-monitoring products, and its Paris partner Sanofi-aventis have launched blood glucose monitoring devices BGStar and iBGStar that connect to the Apple iPhone or iPod touch.

Planned for commercial availability early next year, the devices are intended to help patients self-manage their diabetes. The plug-ins can monitor blood glucose levels, conduct on-the-go testing and communicate results with healthcare professionals.

AgaMatrix and Sanofi-aventis signed a development partnership deal in March, calling for the French firm to combine its insulins, Lantus and Apidira, with AgaMatrix’ blood glucose monitors (BGMs). Under terms of the deal, Sanofi-Aventis will hold exclusive licenses to the BGMs that are co-developed by the two companies and will sell through its Global Diabetes Division. AgaMatrix may continue to commercialize its own BGMs separately from the deal.

AgaMatrix was founded in 2001 by entrepreneurs Sonny Vu of MIT and Sridhar Iyengar of the University of Cambridge. The company incubated for two years in the offices of incTANK Ventures, which provided seed funding for the company.

Read more about the BGStar and iBGStar products.

CAMBRIDGE, Mass. — Most research on renewable energy has focused on replacing the electricity that now comes from burning coal and natural gas. But the spill in the Gulf of Mexico, the reliance on Middle East imports and the threat of global warming are reminders that oil is also a pressing worry. A lot of problems could be solved with a renewable replacement for oil-based gasoline and diesel in the fuel tank — either a new liquid fuel or a much better battery.

Yet, success in this field is so hard to reliably predict that research has been limited, and even venture capitalists tread lightly. Now the federal government is plunging in, in what the energy secretary, Steven Chu, calls the hunt for miracles.

The work is part of the mission of the new Advanced Research Projects Agency – Energy, which is intended to finance high-risk, high-reward projects. It can be compared to the Defense Advanced Research Projects Agency, part of the Pentagon, which spread seed money for projects and incubated a variety of useful technologies, including the Internet.

The goal of this agency, whose budget is $400 million for two years, is to realize profound results — such as tens of millions of motor vehicles that would run 300 miles a day on electricity from clean sources or on liquid fuels from trees and garbage.

One miracle would be a better battery. A pound of gasoline holds about 35 times more energy than a pound of lead-acid batteries and about six times more than lithium-ion batteries. Cars must carry their energy and expend energy to carry it, so the less weight per unit of energy, the better.

David Danielson, an Energy Department official, oversees a program to invest in start-up companies with new approaches to batteries, which is a new strategy; in the early 1990s, the department decided to concentrate all its efforts in lithium-ion research and gave up on other chemistries.

One new technology would allow every car, at modest extra cost, to shut down automatically at each stop sign or red light; when the driver tapped the accelerator, the battery would instantly get it going again. (Hybrids like the Prius do that, but at a substantial cost premium.)

A team at an infant company is using tiny carbon structures called nanotubes to store electricity. The goal is to create something the size of a flashlight battery, holding only about 30 percent as much energy, but able to charge or discharge in two seconds, almost forever.

The technology could form part of the battery pack for a car, cheaply delivering the energy for a jackrabbit start, without damaging conventional chemical batteries, which can store vastly more energy but can only accept or deliver it slowly.

It could also provide a cellphone battery that would charge in five minutes. That kind of battery is called a capacitor.

Joel E. Schindall, a professor at the Massachusetts Institute of Technology and a scientist on the project, pointed out that a capacitor was the original battery. Benjamin Franklin built a set of glass bottles that stored electricity and released it all at once; he called it a battery because, like guns, the bottles fired simultaneously.

But the nanotubes are modern. The walls of the tubes are about 12 atoms thick, and they grow, like leaves of grass, with just enough space between them to provide docking stations for charged particles. So a lot of charged particles can fit into a small space, with very light structures. He compares the device to a book shelf with very thin shelves placed exactly far enough apart to accommodate the books. Because the connection is physical, not chemical, the charged particles can attach and detach almost instantly. The result is a small, light, powerful package.

The project started out with a Ph.D candidate, Riccardo Signorelli, using tweezers to put tiny squares of aluminum into a vacuum chamber and then pumping in a hydrocarbon gas. When heated, the hydrogen burns away and the carbon atoms arrange themselves into tubes. The breakthrough was doing that on a surface that would conduct electricity.

Dr. Signorelli, now with his Ph.D, is chief executive of FastCap Systems, which, with government help, is converting an industrial loft into a factory.

In another M.I.T. lab, Gerbrand Ceder is developing a “materials genome,” using computers to predict the qualities of materials that could be used in batteries, and then fabricating the ones that the computer finds promising. A materials genome would speed the distribution of knowledge about materials and make development of new materials faster, he said, an idea that impresses officials at the Energy Department.

ARPA-E invested $3.2 million in a battery developed with a materials genome in a start-up company, run by Professor Ceder, that is exploring magnesium. In batteries today, whether they are lithium-ion or old-fashioned lead-acid, an atom shuttles between the positive and negative terminal, carrying a single electron, as the battery charges and discharges. But a magnesium atom would carry two electrons, so a battery storing a given amount of energy could be nearly halved in size and weight.

Another approach being financed by ARPA-E is to convert the tremendous amount of energy stored by plants and trees to a car fuel.

Scientists are tantalized by plants and trees because they store far more energy than is consumed by cars, trucks, trains and planes, and they do it by taking carbon out of the atmosphere. But they do not give that energy back in an easy-to-use form, at least not without taking millions of years to turn into oil. Instead, they make energy-bearing sugars in a form called cellulose, which forms the sinew or skeleton of the plant.

Cellulose is hard to break down. “Cotton is pure cellulose,” said Eric Toone, who is Mr. Danielson’s counterpart for biofuels at the Energy Department. “When you take your cotton shirt and put it in a washing machine, it still comes out as a cotton shirt.”

Engineers have tried using steam, acids and enzymes to break cellulose into useful sugars. The enzymes are usually made by gene-modified bacteria or fungi and resemble the saliva of termites, which is notoriously good at dissolving cellulose. So far, none are commercial, but with Energy Department help, some researchers are trying new methods.

Take Michael Raab, whose start-up, Agrivida, in Medford, Mass., is tinkering with the genes of grass and sorghum to develop plants that make the enzymes internally and digest their own cellulose on cue, leaving behind a murky brown concoction of sugars that can be converted into gasoline, diesel or jet fuel.

Deep inside their cells, his plants produce a smooth, nonreactive molecule, but when the plant is exposed to heat and a change in acidity, the molecule breaks open, like a beer bottle smashed against the bar. The jagged edges are enzymes. They rip apart cell walls and leave fragments that are useful sugars.

Sugars — both the common kind that comes in paper packets for coffee and some more exotic types — can be converted by yeast into ethanol, a technology known since ancient times. Or they can be fed to gene-altered bacteria that will excrete diesel or gasoline components. Or they can be converted chemically, with catalysts.

All these steps, including the tricky one of recovering sugar from cellulose, can be done already, but not cheaply enough to produce tens of billions of gallons a year.

The Energy Department is putting $4.6 million into Agrivida, and similar sums into other start-up firms, many of them intent on finding gasoline substitutes. It is, said one department official, “real science fiction stuff,” ideas promising enough to attract a few million dollars for research but not quite promising enough to draw the private capital required for small-scale production.

New financing from the federal government may help biotech companies develop fuels of the future, helping reduce America’s dependence on oil.

One such company is Agrivida, a small, agricultural biotech outside Boston. Until recently, most of its funding came from venture capitalists. The new government financing will ensure Agrivida can continue its ground-breaking work developing crops into biofuels.

“We’re engineering plants so that they can be turned into fuels and chemicals more easily,” says Michael Raab, Agrivida’s President. “We’re working primarily on the green tissues of plants —leaves, stalks, cobs from corn.”

From corn to cellulosic ethanol and biofuels, Agrivida is one of only a handful of small companies to receive funding from the U.S. Department of Energy’s Advanced Research Projects Agency, Energy (known as “ARPA-E”); the Obama Administration funded ARPA-E with $400 million from the federal stimulus package last year.

Modeled after a similar program at the Defense Department known as DARPA, ARPA-E funds “high-risk, high-reward” research. “We’re investing in five or six or seven different ideas and we don’t know which one’s going to win in the end,” says ARPA-E Director Arun Majumdar. “But hopefully if one of them does, the private sector can take it up and scale it.”

Yet, hope alone will not help develop projects like Agrivida’s into large-scale, commercial enterprises. Agrivida needs to raise capital too. Thanks to a new council of corporate heavyweights—including General Electric CEO Jeffrey Immelt and Microsoft Chairman Bill Gates—more companies like Agrivida may get the funding boost they need.

The American Energy Innovation Council is urging the government to triple its investments in clean energy technology to $16 billion a year (including $1 billion a year for ARPA-E). The group says a serious investment will not only protect the environment, but is imperative to ensure our national and economic security.

“There’s going to be a good export market here,” says Chad Holliday, Bank of America Chairman and Chair of the American Energy Innovation Council. “This is a time when we can really be a leader again, like we have been in the past.”

For an in-depth look at the development of alternative sources of energy, watch a CNBC special presentation, “America’s Crude Reality,” Wednesday, June 30 at 8pm ET, hosted by Melissa Francis.

© 2010 CNBC.com

URL: http://www.cnbc.com/id/37995545/

When Jeremy Johnson and R. Michael Raab founded Agrivida in 2005, they were still finishing their Ph.D.s at Massachusetts Institute of Technology. Although both are chemical engineers, they based their start-up not on chemical plant technology, but on a technology for making chemicals in plants.

The work, Johnson says, is a sort of homecoming for a kid from Kansas who grew up working on a small dairy farm. And it is farmers who would benefit from Agrivida’s products. The company is developing specialized crops that manufacture their own enzymes to more easily convert their cellulose into sugars for ethanol production.

Agrivida is one of a number of plant biotechnology firms that are hoping to leapfrog current technologies. Making today’s biobased fuels and materials involves growing crops and then using physical and chemical means to extract sugars that can be fermented into the desired product. The firm’s goal is to make plants do more of the manufacturing work.

For example, biobased plastics firm Metabolix is growing polyhydroxyalkanoate (PHA) resins in switchgrass, and the firm sees a future in biorefineries based on such modified crops. Other companies are forming partnerships in an attempt to engineer chemicals inside crops.

Syngenta is collaborating with research firm Edenspace Systems to develop easier-to-process plants for fuel production. Plant biotech start-up Ceres has worked with Rohm and Haas, now Dow Chemical, to determine whether energy crops could simultaneously produce methacrylate monomers. And Mendel Biotechnology has a partnership with BP to improve dedicated energy crops to speed reactions that break down cellulose and lignin.

Turning crops such as corn, switchgrass, miscanthus, and sorghum into living chemical factories holds the promise of lowering processing costs for renewable fuels and chemicals, proponents contend. Industry analysts agree that the plant biotechnology developments are showing early successes, and they confirm there would be strong demand for the plant-made products.

But for biobased technologies to displace petroleum, farmers will need to gamble on new, risky crops planted on vast acreages. And the new traits do not address questions that face the broader push for cellulose-based fuels and chemicals, including how processors will access and efficiently transport cellulosic feedstocks (C&EN, April 27, 2009, page 10).

It will be a few years before farmers have the chance to plant the new chemical-making crops. In the meantime, research and development of new traits is moving at a brisk pace in the labs of Agrivida and Metabolix, both located near MIT in Cambridge, Mass.

At first glance, the activities at Agrivida’s headquarters look like those at any other analytical lab. Scientists watch over automated machines pipetting small amounts of liquid for screening tests, while biological samples grow in stacks of petri dishes. But a visitor might note a curious-looking plant in the corner. The 4-foot-tall sorghum specimen is a source of genetic material for a team of DNA-transfer experts.

Johnson explains that the researchers are working to modify plant genes to produce a specialized enzyme that breaks down the cellulose in the cell wall. In addition to the enzyme, Agrivida will insert a switch, made from a protein segment, that activates the enzyme under specific conditions.

“Cell-wall-degrading enzymes, though desirable for sugar production, are bad for plant growth,” Johnson points out. With the addition of the enzyme alone, plants soon become limp and die. To preserve plant growth, the company is working with enzyme-arresting protein segments called inteins. “An intein is a peptide sequence within a protein that has the ability to cleave itself out and reconnect the rest of the sequence. That way there is no negative impact on the plant when it is inactive,” Johnson says.

The switch can be designed to splice out under different conditions, such as by heating a crop after it is harvested. Then the activated enzymes would begin to degrade the cell wall and make sugar from the cellulose.

Johnson’s team is working with wild-type enzymes and a selection of the 400 known inteins to find a pair that combines low initial enzymatic activity with high sugar production after the switch is triggered. The result for a cellulosic ethanol maker would be to reduce the need for expensive added enzymes, which can cost up to 70 cents per gal of ethanol. In addition, Johnson says, the sugar could be obtained with less mechanical, thermal, or chemical processing of the plant biomass.

The plants are not yet commercially viable. But Johnson says lab tests show that the modified samples produce a larger amount of sugar than control plants in cases where no enzymes are added, as well as when some or a lot of enzymes are added.

In contrast to Agrivida’s focus on sugar, Metabolix is working to produce plastics and chemicals in plants. The company currently uses sugar as a feedstock to manufacture its biodegradable plastic, a PHA resin called Mirel, through microbial fermentation. Its joint venture with Archer Daniels Midland recently started producing Mirel at a 110 million-lb-per-year facility in Clinton, Iowa.

In March, Metabolix told investors it had successfully produced PHA inside switchgrass plants at a dry weight concentration of 6%. The company can also produce PHA in oil seeds and sugarcane. “Our goal is to get to commercially viable crops in field trials within two years,” says Metabolix Chief Executive Officer Richard Eno. By then, he tells C&EN, the firm will have increased PHA content to a level where producing it inside of plants will be more cost-competitive than fermentation.

To get the most value from the plastic-producing crops, Eno says, they could be processed in a biorefinery. “We would harvest the plants, recover the PHA, and convert it to either polymers or industrial chemicals,” he says. The rest of the plant biomass, he adds, could be used for cellulosic ethanol, gasification, or for fuel in the refinery.

Metabolix is already finding a market for the relatively costly PHA made by fermentation, according to Laurence Alexander, chemicals analyst at the investment firm Jefferies & Co. He told investors recently that with recent Food & Drug Administration approval for Mirel in food contact applications, the firm’s addressable market size is about 4 billion lb per year. “Indicated customer interest to date should suffice to sell out the first commercial plant and justify expansions,” he predicted.

But as other firms enter the biobased plastics market, Metabolix will need to compete on price. “Right now, PHA can withstand a certain premium in consumer products because it is biobased and biodegradable,” says Samhitha Udupa, biobased materials analyst at Lux Research. “But that won’t last more than five to seven years.” Udupa says engineered crops may help get the price down, but she questions the scale the company would have to achieve to gain a sizable share of the polymers market.

All of the plant-based technologies face the same problem of reaching significant scale, Udupa says. “In recent years, venture capitalists and governments have been investing heavily in technology to convert biomass or sugar to chemicals or fuel. We’ve focused on how to get there but not on how much stuff goes into the front end.” The challenge, she says, is growing and accessing the large amount of biomass that would be needed to displace a meaningful amount of petroleum.

At Mendel, Donald M. Panter, senior vice president for bioenergy seeds, is optimistic that farmers will want to plant perennial grasses modified for energy production because they can “make use of secondary land without using inputs or taking away from the food and fiber supply chain.” According to the Department of Agriculture, 38 million acres of idled cropland is available for growing energy crops, if farmers feel they would make a profit.

Large agriculture businesses such as seed firm Monsanto and ethanol giant Poet would make good partners for the biotech firms, Udupa says, because they already have supply chains and distribution channels in place. Johnson agrees, and says Agrivida is looking to enter licensing deals with a large seed company or processor.

Plant biotech executives insist that the industry as a whole is developing more efficient technologies and processes that will make growing, collecting, and processing biomass for energy and chemicals profitable. But for now, the promise of large-scale cellulosic fuel production has yet to be fulfilled, and that concerns Johnson. “For our model to be truly successful, we’ll be somewhat dependent on the success of others,” he says.

Chemical & Engineering News
ISSN 0009-2347
Copyright © 2010 American Chemical Society

Ligon Discovery has been discovered, and I could argue that I was there the moment it happened. Patrick Kleyn, co-founder and CEO of Ligon, was sitting in the back of a crowded conference for drug industry dealmakers in Harvard Square last month when a senior pharmaceutical executive on an industry panel noted Kleyn’s fledgling firm as one of the promising young life sciences companies in the Boston area. Kleyn was seated next to me, and I saw him beaming after receiving the shout-out.

There are a few ways to get discovered as a new biotech startup: exciting science, big-name founders, success in raising venture capital, or any combination of these. Ligon falls into the “exciting science” category, because its small-molecule microarray technology could revolutionize the way researchers go from identifying a potential disease protein or target to finding a drug that can home in on that target. It’s been just a year since Cambridge, MA-based Ligon spun off from the Broad Institute of MIT and Harvard, and the firm is already generating some positive buzz at venues like the Boston Biotech Business Development Conference in Harvard Square last month.

Ligon might have the right technology at the right time. Genetic research has uncovered a plethora of proteins in recent years that play key roles in human diseases. Yet it can take several months or more than a year to design a test or assay that can be used to screen libraries of small molecules for ones that can bind to the newly uncovered disease proteins. Ligon’s technology is designed to greatly reduce those long turnaround times in drug discovery.

“One of the key benefits for a [pharmaceutical] company, when you talk about time to market, is the ability to go from an idea of screening certain targets to looking at structures or hits from a screen within weeks,” Kleyn says. “Whereas, a very typical turnaround time for that [process] in a large pharmaceutical company would be a year plus.”

Ligon’s technology borrows a concept from open-source software development for designing tests for drug discovery, says Kleyn, the former director of scientific planning for the Broad Institute. While open source gives programmers common codes for developing software, Ligon has a single form of chemistry that can be used to make any number of drug-screening assays. Angela Koehler, a chemist at the Broad Institute and co-founder of Ligon, discovered several years ago that an isocyanate chemistry could be used to bind a majority of small molecules to glass slides used to find drug candidates, without requiring time-consuming chemical modifications that are typically required to develop such tests.

The startup can use the chemistry to attach thousands of small molecules onto slides, which are used to identify molecules that bind to disease proteins in a high-speed screening process. The chemistry enables Ligon to link more than 75 percent of the small molecules in a typical compound collection to the glass slides, providing them the ability to screen hundreds of thousands of molecules against dozens of protein targets at the same time, according to Ligon. Koehler (who made the company’s key discovery with colleagues in the standout chemist Stuart Schreiber’s lab at Harvard) has in recent years published numerous research papers that demonstrate its use in identifying drug candidates against transcription factors and other proteins that have historically proved very challenging for drug discovery.

Ligon has a two-pronged business strategy to exploit Koehler’s discovery, according to Kleyn. First, the company is seeking partnerships with drug companies that would pay to use the startup’s technology as well as provide future payments based on the success of drugs it discovers with the technology. Thus far, the startup has formed such a partnership with the Cambridge, MA-based biotech Lycera, which plans to use Ligon’s technology to discover small molecule drugs for immune disorders. (Last week Lycera, which is covered by Xconomy’s new Detroit site because it has a key R&D site in Plymouth, MI, raised $11 million from investors.) The second prong of Ligon’s strategy is to use its technology to discover its own drugs against difficult-to-drug targets like protein-protein interactions. Ligon has completed initial screens against over 50 such targets and is now moving ahead with its first drug candidates in cancer, inflammation, and metabolic disease.

Kleyn says that his firm is in talks with multiple potential partners, the names of which he was unable to disclose because of confidentiality concerns. However, it came to light during the Boston Biotech Business Development Conference in April that Ligon had met with executives at the London-based drug giant GlaxoSmithKline’s Center of Excellence for External Drug Discovery (CEEDD), which does option-based deals with biotechs to enhance Glaxo’s pipeline of potential drugs. Michelle Dipp, the head of the CEEDD, mentioned her outfit’s interaction with Ligon during the conference but did not disclose the nature of talks between her group and the startup.

Nevertheless, the buzz about Ligon bodes well for its future. Kleyn says that his firm, which raised $1 million in seed money from the investment firm IncTANK Ventures last year, wants to raise between $3 million and $5 million in a Series A round of venture capital. The money would help fund its internal drug-discovery efforts and support its search for new partners. The Ligon crew knows how to raise cash for biotech startups. Kleyn was chief scientific officer for Gemini Genomics (now part of San Diego-based Sequenom), where he took part in the firm’s $96 million initial public offering. Ligon has also recruited Errol De Souza, the former CEO of Cambridge-based Archemix, as its chairman.

Now that Ligon’s been discovered, the startup faces the even bigger challenge of finding a drug that can go the distance in human clinical trials. We’ll see how they handle this hurdle in the coming years.

Ryan McBride is Xconomy’s correspondent. You can reach him at rmcbride@xconomy.com, or follow him on Twitter at http://twitter.com/Ryan_McBride.