June 1, 2009 (Vol. 29, No. 11)

Carol Potera

Established Biotech Cluster Takes the Lead In Reducing Country’s Dependence on Fossil Fuels

San Diego has been a leading hub of the biotech industry, starting with the formation of Hybritech in 1978, a pioneer in mAb-based diagnostics and treatments. Now the San Diego region is at the forefront of one of the newest biotechnology clusters known as cleantech or greentech, which aims to reduce our dependence on fossil fuels through innovative life science strategies.

In 2007, CleanTech San Diego was formed with the mission to stimulate innovation and adopt clean technologies and sustainable industry practices. Today’s cleantech pioneers continue to leverage local academic and business talent. “We need to feed innovations to discover and commercialize new technology to reduce our carbon footprint and improve the economy of San Diego,” says Lisa Bicker, president of CleanTech San Diego, a nonprofit organization.

Room Temperature Biostability

Biomatrica’s green technology allows life scientists to store biological samples at room temperature, rather than in -80ºC freezers. “We were surprised how much energy labs can save by eliminating freezers,” comments Rolf Müller, Ph.D., cofounder and CSO.

In a yet unpublished study conducted at Stanford University in collaboration with Stanford’s Department of Sustainability and Energy Management, about 800 freezers operating at -80ºC were counted in various science buildings. An independent analysis found that Stanford University could save 160,000 million BTUs, reduce its carbon footprint by 15,000 tons of carbon dioxide, and generate a net cost savings of $16 million over 10 years by storing biological samples in Biomatrica’s kits.

The current kits offered by Biomatrica stabilize purified RNA and DNA or blood samples for long periods. The kits contain reagents to coat samples with a dissolvable glass shield. “We shrink-wrap biomolecules in a protective shell to reduce Brownian motion,” explains Dr. Müller. Accelerated aging experiments, in which encased DNA samples are subjected for two years to high temperatures equivalent to 30 years at room temperature, confirm that no degradation or sample loss occurs, he adds.

Samples are glass stabilized on the bottom of tubes or in 96-well plates supplied with the kits. RNAstable™ preserves and stabilizes RNA and Poly(A) mRNA samples, and DNA SampleMatrix® protects plasmid and genomic DNA at room temperature storage.

Qiagen licensed Biomatrica’s first DNA stabilization kit just nine months after it was launched and now markets it as QIAsafe. “That’s a big deal for a young company with a nascent technology,” says Judy Müller-Cohn, Ph.D., cofounder, president, and CEO of Biomatrica.

The Müllers were inspired to create their energy-saving technology while pondering how extremophiles such as dried brine shrimp, often sold in toy stores, can survive for 100 years and then be revived when hydrated.
Both scientists worked in high-throughput (HT) laboratories where 10,000 samples were generated daily and stored in -80ºC freezers. They knew firsthand that sometimes freezers break down and valuable samples are lost. They used HT methods common to drug discovery to probe how extremophiles naturally survive stress, then they screened combinatorial libraries to find alternative chemical stabilizers.

“For each biological sample, we have to find the best glass to stabilize it, depending on surface structure,” says Dr. Müller. New kits are being developed to stabilize proteins, microorganisms, and eukaryotic cells, which will reduce lab freezer costs even further.

Biomatrica’s biological sample-stabilization technology allows samples to be stored at room temperature rather than in freezers.

Chemicals from Microbes

A sustainable method to make high-value chemicals from sugar was invented at Genomatica. In addition to refining crude oil into gasoline for automobiles, refineries “crack” or process crude oil into higher-value industrial chemicals such as 1,4-butanediol (BDO) and methyl ethyl ketone (MEK). Genomatica has discovered a way to make both these chemicals from sugar in microorganisms, bypassing the need for oil.

Started in 2000, Genomatica first created and sold computational software to model how cells function and their metabolic pathways. “In the past two to three years, we used our computational models to design microbes to make chemicals,” says Christophe Schilling, Ph.D., president.

In September 2008, Genomatica reported on a biomanufacturing process for BDO in Escherichia coli that starts with sucrose. With its computational modeling software, the company’s researchers examined all possible biological pathways for making BDO from sugar (about 40,000), then they selected the best pathway and enzymes. After genetically engineering six enzymes into E. coli, the microbe generated BDO within six months. “E. coli or any other organism was never known to make BDO before,” explains Dr. Schilling.

The microbe-based process is designed to make BDO at a lower cost than petroleum-based methods. Since the results were made public, three-quarters of BDO producers worldwide have contacted Genomatica to learn about the method, according to Dr. Schilling. “Producers find it appealing to start with a renewable source and like the environmentally friendly angle,” he adds. The method has been scaled up in the laboratory to 30 L volumes and a demonstration plant is planned for large-scale fermentation. BDO, a precursor of Spandex fibers and thermoplastics, has a worldwide annual production value of $4 billion.

A similar computational modeling method led to the generation of MEK from sugar in bacteria, which the company reported in February. MEK is a common solvent in paints and varnishes, and its global market is valued at $2 billion. Moreover, the sustainable chemical processes for making MEK can be readily transferred to equipment at bioethanol manufacturing facilities, some of which have been left idle by recent market contraction. 

Enzyme Cocktails for Biofuels

Verenium, formed in 2007 by the merger of Diversa and Celunol, is building a demonstration plant in Louisiana, which the company says will produce 1.4 million gallons of cellulosic ethanol from agricultural waste yearly. The Louisiana location provides a steady supply of feedstocks, a long growing season, and access to gasoline-blending facilities. A partner in the endeavor is BP, which brings $90 million in funding.

According to the Energy Industry and Security Act of 2007, 16 million gallons of ethanol annually must be made from biomass by 2022. “Today, there are zero gallons of ethanol made from biomass, so this industry has to be created,” says Janet Roemer, GM of Verenium’s specialty enzyme business.

The enzyme expertise of former Diversa scientists is helping to maximize the breakdown of cellulosic biomass to sugars for fermentation into ethanol. Diversa scientists traveled the world in search of enzymes that thrive in hostile environments such as geysers in Yellowstone National Park. Now, those libraries are being screened to find enzyme cocktails to speed the production of ethanol from diverse feedstocks such as bagasse (sugar cane refuse) and energy cane.

Energy cane, a nonfood cousin of sugar cane, generates up to 1,830 gallons of ethanol per acre. In contrast, corn makes about 400 gallons of ethanol per acre and switchgrass about 700 gallons per acre. “The enzymes we are using at the demonstration plant are the best we know of today,” says Roemer. Verenium, however, continually looks for improved enzyme cocktails to drive costs down and raise its competitive edge.

Substance, Not Hype

Crude oil doesn’t only come from oil wells; some plants make oil in their seeds that could be used for making biodiesel or bioplastics. SG Biofuels focuses on Jatropha curcas, a fast-growing, nonedible shrub that grows wild in Central America. Its seeds contain up to 40% oil, which “is of excellent quality for making biodiesel and for blending with aviation fuel,” according to Robert Schmidt, Ph.D., chief scientist at SG Biofuels and a plant biologist at the University of California San Diego. Unfortunately, “there’s been lots of hype, but little credible development of Jatropha,” adds Kirk Haney, president and CEO.

Current yields of oil from cultivated Jatropha reach 200–300 gallons per acre, which is five times more than from soybeans and twice that of canola yields. Classic plant-breeding experiments, now under way in greenhouses, will substantially boost the oil content of seeds and allow Jatropha to grow in colder temperatures. Additionally, Jatropha is a nonfood crop, sparing it from a public backlash by those opposed to deriving biofuels from food crops.

Once Jatropha is genetically improved, “production costs for the oil could be well under $1 per gallon,” says Haney. The company is developing Jatropha plantations on marginal land in Central America. The plants’ seeds will be crushed to produce crude oil to sell to local refineries. “We have a platform that will grow for the next five to ten years,” predicts Haney.

Like Jatropha, microalgae are another potential source of oil often surrounded by more hype than substance. Mario Larach, chairman of Kai BioEnergy, plans to bring a credible voice to microalgae.

Kai is the Hawaiian word for ocean, which is suitable for the firm since its technology is based on marine diatoms that produce light sweet crude oil of a quality suitable for aviation fuel. “The fuel produced by microalgae probably will be better than fossil fuels because it is not contaminated with sulfur,” says Larach.

Kai BioEnergy holds a patent from the University of Hawaii that insures the growth of diatom monocultures, and it  invented an environmentally friendly, water-based extraction method to pop open diatoms to release the oil.

One acre of microalgae can yield up to 15,000 gallons of ethanol. Other advantages of microalgae include its preference to grow on substandard land in brackish salt water. Microalgae also require carbon dioxide, so production ponds can be placed near power plants to capture and recycle the polluting greenhouse gas. Moreover, the diatom shells, which are 60% high-quality silica, can be recycled as a filtration material.

Kai BioEnergy developed its prototype methods on a half-acre pond in Hawaii. Now Larach is scouting for 50 acres near  San Diego to scale up production. “San Diego is an optimal location because of its scientific talent, access to farmland, ideal weather, and huge demand for clean energy products,” says Larach.

SG Biofuels makes biodiesel from Jatropha curcas, a nonedible shrub that grows wild in Central America.

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