JBEI spins out Lygos to commercialize sugar-metabolizing microbes

The U.S. DOE’s Joint BioEnergy Institute (JBEI) has spun out its first company, Lygos. The technology developed at JBEI, which will be commercialized by the new company, features designer microorganisms that metabolize sugar and can produce a wide variety of molecules.

According to information released by Lawrence Berkeley National Laboratory, which leads JBEI, the technology essentially repurposes a class of proteins that have been used for decades to make antibiotics and other drugs. Polyketide synthases are a (PKS) are a family of multifunctional enzymes that produce polyketides, hydrocarbon chains that serve as the backbone for many natural and synthetic organic chemicals. The JBEI researchers redesigned the PKS pathway by mixing and matching genetic information to produce compounds that were never made by nature but are used in everyday synthetic materials.

Recent technical advances such as high-throughput screening and low-cost DNA synthesis has allowed us to make smaller versions of these pathways, said Lygos President Clem Fortman. While the process has traditionally been used in the pharmaceutical industry to produce complex drug molecules, the JBEI team has been able to pare down the process to make much smaller molecules, including common industrial chemicals.

Fortman said that one of the benefits of the process is that it is extremely output-flexible. In fact, the technology can produce a wide range of molecules, including nylon precursors, polyester components, styrene and propylene. LBNL also stated that Lygos’ technology can also be used to engineer products with characteristics that have never been achieved before, or that have been too expensive to produce using other methods. In addition, the technology can be used to produce biofuels.

Although other companies are using biological processes to make certain compounds, LBNL said the aspect of Lygos’ technology that make it superior is that it is a platform as well as a process, which theoretically allows for a huge number of molecules. PKS are composed of discrete modules, each catalyzing the chain growth of a single step. Synthesis of a desired compound can be programmed by selection and genetic manipulation of PKS.

There are several other unique aspects of the process beyond its inherent flexibility. Since everything is built from central metabolic precursors, there is no need for complex precursor engineering, Fortman said. It’s also a fairly mobile platform, he said, noting that these types of enzymes are found in a number of bacteria, as well as in plants. “If you have bacteria that eat your feedstock very efficiently, tuning it to use polyketides should be relatively straightforward,” Fortman added.

Lygos is currently working to optimize production of its first target compounds. While Fortman could not disclose specifically which molecules his company will target first, he did note that Lygos is pursuing chemicals before biofuels. “It’s a faster pathway to revenue stream that will allow us to build the company more quickly and get the infrastructure built out,” he said.

So far, the technology has been used to produce compounds on a lab scale. According to Fortman, the company will continue to work on the lab scale for the remainder of the year. He said pilot-scale evaluations could begin in a year or two. Rather than constructing its own pilot facility, Fortman said that Lgyos will likely initially work with an existing pilot-scale facility within the JBEI building, which can be utilized on a contract basis.