"This was our first experience designing and ordering hundreds of genes at once, and it was a game-changer for us in advancing our technology. We struck out several times and learned things we weren’t expecting, but we also made huge strides."
In August 2015, Industrial Microbes became the first company to win Gen9’s G-Prize startup track. Gen9 launched the G-Prize in 2012 and exclusively sponsors the contest to foster creativity and innovative approaches for using synthetic DNA.
Industrial Microbes team. Left to right: Baolong Zhu, Derek Greenfield, Stephanie Jones, Liz Clarke, Noah Helman, Olivier Marie.
Focused on producing environmentally-responsible chemicals using methane as a raw material, the Industrial Microbes team used the 500,000 base pairs of synthesized DNA awarded by Gen9 to evaluate and optimize untested and newly discovered enzymes for use in their synthetic biology platform.
Industrial Microbes chose methane as its raw material because the founders learned that the use of traditional sugars as a feedstock can be a major bottleneck associated with synthetic biology. Sugar is expensive and its cost can prevent synthetic biology products from being commercially viable.
Methane is both inexpensive and relatively abundant, found both below ground and under the sea floor, and produced in wastewater treatment as renewable biogas. By using methane as an alternative feedstock, Industrial Microbes could produce a valuable product at a much lower cost.
“Our challenge was to create a synthetic pathway in yeast to consume methane since yeast doesn’t naturally do that,” continued Helman. “The enzymes able to do that conversion don’t exist in yeast and must be expressed correctly to function. The G-Prize allowed us to test several design variations of that genetic pathway.”
Helman explained that several enzymes can do the chemistry, however most have not yet been tested and none had been expressed in yeast.
“We don’t know as much about engineering biology as we think we do,” said Helman. “For example, a year ago, we were working on a project to develop a novel pathway to an industrial chemical product where we had identified two genes we thought might work. We designed and ordered 10 homologues of each gene and tested all the possible combinations. Only one combination worked. For that reason, the best strategy is to cast a wide net and try multiple designs.”
Helman noted that having Gen9 synthesize DNA made his team significantly more productive by reducing the time needed to manipulate DNA. Even better, the team is able to test 10 to 100 times more DNA with the same effort, since construction is no longer a bottleneck.
When asked what he would do with another 500 kb of DNA, Helman answers, “The G-Prize was a big step forward. It helped us to be more creative and expand the range of experiments we tried. Another award would allow us to focus on developing pathways that code for important chemical products and land our next set of deals.”