(417d) Development of a Natural Gas to Industrial Chemicals Bioprocess Platform

The low cost and abundant supply of natural gas have been motivators for the development of many technologies that convert this feedstock into compounds of greater value. Intrexon has developed the first natural gas-to-liquids bioconversion platform powered by methantrophic fermentation, which applies synthetic biology to program bacteria to produce higher value materials of interest. Our innovative genetic toolbox allows us to engineer the biology of the methanotroph to more efficiently convert natural gas into a wide range of valuable chemicals and fuels. These applications include isobutanol, farnesene, 1,4-butanediol, 2,3-butanediol, isoprene and isobutyraldehyde – the building blocks for industrial and consumer products like fuels, synthetic rubber, acrylics, resins and spandex.

Using a methanotrophic bioprocess to produce fuels and chemicals has several advantages beyond the low cost and minimal processing of feedstock. Natural gas bioconversion offers scaling opportunities beyond traditional gas-to-liquid (GTL) facilities, as well as biomass feedstock facilities. Theoretical yields using the methanotroph and methane exceed that of yeast/sugar approaches by a wide margin. Biocatalytic processes that achieve high yields under milder processing conditions allow for reduced capital and operation expenditures, offering greater economic viability. The natural gas bioconversion also does not compete with food resources, unlike traditional biofuels that use sugar and corn as feedstock.

One molecule of interest in the methanotroph platform is isobutanol, a fuel for gasoline blending which has several positive attributes. Isobutanol is a clean burning and non-corrosive “drop-­in” fuel which can be blended with gasoline and is compatible with the existing petroleum infrastructure. Currently, provisions allow for bio-butanol blending up to 12.5% with gasoline and ASTM specifications exist for sale as fuel. Every 1% of isobutanol blended with gasoline presents an $8 billion market opportunity. Combustion of isobutanol has cleaner emissions compared to gasoline by reducing hydrocarbon, carbon monoxide, nitrous oxide and sulfur dioxide production. Isobutanol also has advantages over first generation biofuels, such as ethanol, because of its higher energy density.

Intrexon Energy Partners was formed as a joint venture to commercialize the production of isobutanol from natural gas using a methanotroph. Gas fermentation processes were developed to evaluate growth of the bacteria and production of isobutanol from the microfermenation scale through the lab and pilot scales. The ability of our modified methanotroph to produce isobutanol has increased exponentially with time as the genetic toolbox was developed and early learnings in strain engineering were optimized into a design-build-test-learn cycle. A state of the art laboratory was custom built to bring research and development from a low throughput and manual process to a high throughput automated process. Increases in automation and throughput have positioned Intrexon as a leader in the genetic engineering of methanotrophs and accelerated the commercialization timelines of other chemical products.

To successfully bring this technology to commercial scale, consideration must be given not only to optimizing the metabolic pathway engineered into the methanotroph, but also to key issues in the fermentor design and downstream processing. Laboratory scale learnings were applied to select technology that was commercially feasible at demonstration scale. Since the substrate is a gas, the design of the fermentor must be optimized for effective mass transfer of the natural gas to the liquid phase for increased bioavailability. Downstream processing must take into consideration purification of the isobutanol and removal of fermentation byproducts and contaminants. Process selection must weigh the efficiency and selectivity of technology options, while at the same time, utilize as much mature technology as possible to minimize risk. The project team has performed numerous design reviews known as Front End Loading (FEL) to develop process criteria and scenarios

Beyond isobutanol, Intrexon’s versatile platform strategy has accelerated the development of 2,3-butanediol, 1,4,butanediol and isobutyraldehyde platforms. Production of these intermediate chemicals has expanded the value of the natural gas conversion technology from the fuels market to consumer markets like tires and textiles. The commercial fermentation design optimization occurring in the pilot plant may also be applicable to other chemicals, shifting the focus of future products to downstream development.