Biotechnology Reenergized

TAKING THE LEAD

The DOE is credited for launching the HGP, and as a founding member of the International Human Genome Sequencing Consortium, determined the sequences of chromosomes 5, 16, and 19. The DOE also established the Microbial Genome Program (MGP), which since 1995 has supported microbial biology research and sequenced nearly 200 microbial and related genomes and 12 microbial community genomes. Much of the DOE's success of its relatively modest biological program rested on its position within the behemoths of the physical sciences, including scientific computing. That close relationship emboldened the DOE biology managers to access many of the physical and computational science tools that helped fuel this revolution.

With the completion of the HGP and the evolution of the MGP, the new engine of the DOE's biotechnology effort is the Genomes To Life (GTL) program. Conceived and designed by our scientific advisors, GTL is a joint undertaking by the biology and high-performance computing science offices of the DOE. GTL focuses primarily on microbes and microbial communities and is aimed at applications of clean energy production, bioremediation of mixed (radioactive and chemical) wastes, and enhanced carbon sequestration by the biosphere.

The scientific focus of GTL is on the multiprotein molecular machines within cells and the regulatory networks that drive them. All experimental and high-end computing efforts are driving toward a robust predictive capability that can help design the systems that will deliver applications important to the DOE. Existing and new tools will be absolutely necessary to realize the GTL goals, including the DOE sequencing factory at Walnut Creek, Calif.; the X-ray, neutron, and nuclear magnetic resonance sources; the DOE supercomputers; and a new generation of proposed user facilities such as those for protein and molecular tag production, imaging, and proteomics.

Launched in 2002 with current funding at $68 million per year, GTL funds large multidiscipline, multi-institution teams that are self-organizing and adopting a big-science approach to specific problems they are tackling. Although still relatively new, GTL is showing tremendous promise both for breakthroughs of intrinsic scientific value as well as for delivering on the DOE missions within reasonable time frames. Among several worthy examples of GTL and related projects, I will briefly describe three that in many ways have motivated my bullishness about the potential for this program.

CLEANUP, ENERGY, AND SEQUESTRATION

Derek Lovley at University of Massachusetts at Amherst and his team focus on microbial Geobacter species.¹ The team has demonstrated how these microbes can effectively reduce soluble uranium (VI) to insoluble uranium (IV) and thus immobilize these radionuclides and other toxic metals from contaminated groundwater. Subsurface uranium is a serious environmental problem at many of the DOE sites around the United States where nuclear weapons were manufactured during the cold war. The capacity of naturally occurring Geobacter species to transfer electrons to oxidized metals can be stimulated simply with the addition of an acetate solution to the groundwater.

The second example comes from the laboratory of the J. Craig Venter Science Foundation. Venter and his team are inventing ways to produce a synthetic genome.² Having achieved their goal for a virus, they now have their sights set on a microbial genome. One of their objectives is to synthesize the "minimal" microbial genome in order to focus investigations solely on aspects of microbial biochemistry that are of interest to GTL. Creating the minimal genome of a hydrogen-producing extremophile, for example, may provide valuable insights into ways to produce hydrogen on an industrial scale.

Courtesy of Michael Himmel

Cellulases are a broad family of enzymes that convert cellulose to glucose. The exoglucanase starts at a nick in the cellulose and proceeds down the track, converting the polysaccharide to double glucose molecules that are then split by another cellulase. The exoglucanase has three distinct domains: catalytic, linker peptide, and binding domains. The binding domain on the right extracts the track of polysaccharide from the cellulose and presents it to the active reaction site within the catalytic domain (From M. Himmel et al., "Cellulase Animation," run time 11 min., National Renewable Energy Laboratory, Golden, Colo, 2000, doi:MRI PAU2-568-354)

The third example started at the DOE Joint Genome Institute with the sequencing of a Populus tree, a common biomass crop. Plans are in place to also sequence the genomes of the microbial communities in the root zone of the Populus. Discovering the genes and gene regulatory networks that control the shape and the partitioning of carbon throughout the tree as well as the principal drivers of growth will create exciting opportunities for enhancing its biomass potential and increasing the carbon sequestration capacity in ways that can help reduce the carbon loading of the atmosphere from fossil fuel burning.⁴

Such advances may soon aid in realizing a consolidated bioprocessing system for the creation of ethanol as described by analyst Charles Mann in his report to the National Commission on Energy Policy.⁵ This system would move several processes associated with biomass to ethanol production into a single (genetically modified) organism that both breaks down the cellulose and other biomass constituents into sugars and ferments the sugars to ethanol. Mann estimates that this could increase the conversion efficiency from 36% to 70%.

Steven J. Smith and colleagues at Pacific Northwest National Laboratory in Richland, Wash., describe how the generation of bioethanol may evolve over a decade, leading to the displacement of 35 billion gallons of gasoline per year without impact on land currently dedicated to food production. If Mann's suggested improvements can be made by 2020, this technology could displace 22% of U.S petroleum imports.⁵

Although there is no experience yet comparing the cost and effectiveness of bioremediation of metals and radionuclides with traditional methods, costs savings for bioremediation of organics are estimated to range from 30% to 95%. In situ bioremediation, taking advantage of natural microbial populations in the subsurface, has the potential for reducing costs and increasing the efficiency of groundwater treatment as compared to conventional pump-and-treat technology. More than one billion cubic meters of water and 55 million cubic meters of solid media at the DOE sites in 29 states are contaminated with radionuclides. Cost estimates for restoration of these sites start at about $200 billion, so the potential savings accrued by use of innovative technologies may amount to many billions of dollars.⁶

Fast-growing biomass plantations will take advantage of biotechnology to increase the efficiency of biomass production without constraining the production of food and fiber. An additional benefit will be the augmentation of greenhouse-gas mitigation through increased carbon sequestration in the soils of these managed terrestrial ecosystems. Stan Wullschleger at Oak Ridge National Laboratory in Tennessee estimates that by increasing the lignin concentration of roots, thereby increasing the turnover time, an additional 0.35 GtC/year (gigatons of carbon-per-year) could be sequestered globally during a 30-year poplar rotation.

Although some genetic engineering may be pursued in laboratory studies, it is entirely possible that no genetically engineered organism will ultimately be released to the environment for the GTL-derived applications. Through environmental genomics we are discovering such diversity in nature's tool-kit that it may suffice to simply "pick and choose and encourage" natural systems to realize the GTL applications in energy and environment. Advances such as the ones described are indicative of the acceleration in scientific innovation fueled by high-throughput processes. I believe that GTL can be the engine for innovation.

Aristides Patrinos is the director for biological and environmental research in the Office of Science at the US Department of Energy. He led the DOE effort in the Human Genome Project as well as the expanded DOE program in the study of global environmental change. More information about Genomes To Life can be found at http://www.DOEGenomesToLife.org.

He can be contacted at ari.patrinos@science.doe.gov.