Greener Synthetic Pathways Award: Genomatica, San Diego

Industrial biotechnology company Genomatica, based in San Diego, took home the Greener Synthetic Pathways Award for inventing a low-cost, direct microbial fermentation route to the large-volume chemical 1,4-butanediol (BDO) from renewable carbohydrate feedstocks. The route, which represents Genomatica’s first product, demonstrates a systems-based metabolic engineering approach to microbe design and development that could enable bioprocesses for other commodity chemicals that are not naturally produced by cells.

“Our goal is to generate process technologies that harness the power of nature to convert renewable feedstocks into high-volume commodity chemicals,” says Genomatica cofounder and chief executive officer Christophe Schilling. “The Green Chemistry Award speaks not just to the success of biobased BDO but the potential of our technology platform that we think will allow us do the same for a broad range of chemical targets with economics that can compete head on with petrochemicals.”

Approximately 2.8 billion lbs of BDO with a market value of $4 billion are manufactured globally each year in multistep processes from petroleum-derived feedstocks such as acetylene, propylene oxide, and butadiene. BDO is widely used in the production of solvents, fine chemicals, and high-performance polymers. For example, it’s an ingredient in spandex fibers used in performance apparel, engineering plastics such as polybutylene terephthalate used to make car dashboards, protective casings for small home appliances, and the soles of running shoes.

Genomatica’s process, which originated in the lab of University of California, San Diego, chemical engineer Bernhard O. Palsson, represents one of the most complex metabolic engineering endeavors to date, Schilling says, going significantly beyond the fermentation technology that produces ethanol and other small molecules.

To make BDO, sugar is fed to an engineered strain of Escherichia coli, where it is converted through glycolysis and the Krebs cycle to succinate-based metabolites. These metabolites are transformed by a set of enzymes derived from different parent organisms to hydroxybutyryl intermediates and then to BDO (Nat. Chem. Biol., DOI: 10.1038/nchembio.580). The fermentation broth goes through cell separation, salt separation, water removal, and purification steps, leading to BDO with greater than 99.5% purity.

The bio-BDO process was initially validated in a 3,000-L fermenter by the nonprofit industrial biotech development firm MBI, in Lansing, Mich. The fermentation has been scaled up to 13,000 L with Genomatica’s business partner Tate & Lyle at a demonstration plant in Decatur, Ill., which can produce two tons of polymer-grade BDO per week. This demo operation will provide data to prepare the complete engineering package for construction of commercial-scale biobased-BDO plants, Schilling says, with the first ones expected in 2014.

Genomatica’s strategy will be to build low-cost plants located near feedstock sources and/or downstream plants, Schilling says. The company will also “right-size” the facilities to accommodate the local feedstock supply and product demand, a strategy that Genomatica anticipates will reduce transportation fuel costs and emissions. In addition, the versatile microbe can consume different sugar feedstocks, including glucose, xylose, sucrose, and mixed biomass-derived sugar streams, he adds. Thus, production plants can use whatever feedstock makes most sense in a given geographic region, further reducing costs and the environmental footprint.

Life-cycle analyses indicate that BDO production from sucrose will reduce CO₂ emissions by nearly 70% relative to BDO production from petrochemicals, Schilling notes, in part because the biobased BDO incorporates carbon from CO₂. The process also uses about 60% less energy relative to petrochemical BDO production, he says, with the savings coming primarily from operating at lower temperature and pressure. The most abundant material used in the biobased BDO process is water, which is recycled—no organic solvents are required.

Several large chemical companies have successfully used Genomatica’s BDO samples for downstream testing and processing, he adds. On the basis of those early results, Genomatica projects capital costs to be 50% lower and commercial-scale operating costs to be 15 to 30% lower than those of petroleum-based processes.

Genomatica’s platform technology focusing on pathways to high-volume chemicals carries an important advantage over bioprocesses that focus on a single platform chemical, which might be made at lower volumes and then used to make other chemicals, Schilling believes. For example, some bioprocesses are being developed to produce succinic acid (see BioAmber’s Small-Business Award). Additional chemical processing steps are then required to convert succinic acid to large-market chemicals such as BDO or into polymers, which increases operating costs, capital equipment costs, and environmental footprint.

Genomatica’s technology platform “is agnostic to the end use of the chemical target, so it allows us to go after a broader mix of molecules,” Schilling says. “We currently have an intellectual property portfolio that covers some 25 of the largest volume commodity chemicals that we think can be attractively made using biotechnology. We are really looking forward to using our approach and partnering with the chemical industry to drive its transformation to a new era of sustainability.”