The Bio Incredibles

Yes, it’s the Bio-Incredibles, synth biologists with recombinant powers and abilities far beyond those of mortal men.

Bio-Incredibles: who can change the course of mighty genomes, bend DNA in their bare hands.

Hidden in Emeryville, California, mild-mannered high-tech center for a great metropolis, they fight a never-ending battle for science, progress, and a Series A investment round.

In today’s Digest: the Bio-Incredibles at Industrial Microbes. 

In the pivotal car chase in the first few minutes of The Incredibles, you hear a reference to San Pablo Avenue, and on the radar screen flash up a whole bunch of familiar streets. Yep, they’re all taken from Emeryville, California — the home of Pixar, the film’s creator.

But there’s something even more incredible happening in Emeryville than the adventures of Mr. Incredible, Elastigirl, Syndrome and The Dash — though super-powers may well prove to be something that are being engineered into microbes all over town, as we speak. Emeryville has emerged as the epicenter of the next wave of synthetic biology, nanotechnology and the new materials companies — where far-out ideas exist as a new normal.

Who’s there?

Organizations like Amyris, Total New Energies, Mango Materials, Caribou Biosciences, Kiverdi, Lygos, Lawrence Berkeley’s Advanced Biofuels Process Development Unit, Slingshot Biosciences, JBEI, Dagamite, 6SensorLabs and Radiant Genomics.

What are they up to?

One of the opportunities that has, of late, been driving a series of company formations has been the rising interest in methane as a substrate. Simply put, the carbon in methane is available for roughly one-third the cost of the the carbon in sugars.

One of the reasons that you don’t hear as much anymore about “the glucose economy” as a replacement for “the hydrogen economy”, which I think replaced the “atomic economy” after we were through with the “petro economy” and the “coal economy”. Somewhere back in time, there was probably a Stone Age equivalent of the Harvard Business Journal, touting the “wheel economy” and the “flint economy”.

For now, sigh, we have the methane economy. And natural gas prices are expected to remain low enough, for long enough, for Bay Area researchers to park their concerns about fossil fuels and develop a transformative series of technologies using methane. Calysta Energy is one such company we’ve shined a spotlight on in recent weeks.

Two, two, two greenhouse gases in one.

But one company is chasing something even more interesting than methane — and that’s the combination of methane and CO2 as twin substrates. Can you use methane to sequester CO2 by developing green materials and chemicals that utilize both of these potent greenhouse gases, at once?

That’s the quest the Industrial Microbes is on — founded by a trio of former LS9ers – Derek Greenfield, Elizabeth Clarke and Noah Helman.

A few weeks back we noted that they picked up $500,000 in the latest round of Albert’a CCEMC Grand Challenge, an Alberta-based $35M grant program that funds important emerging technologies to capture and utilize carbon dioxide. As a Grand Challenge finalist, Industrial Microbes will receive its award over the next two years to fund development of its fermentation technology to create products from CO2, and an opportunity to compete for $3M and $10M CCEMC grant awards in 2015 and 2017.

What’s so special about CO2 and methane?

Well, they’re potent greenhouse gases — and both are potentially available at rock-bottom prices. Which makes any technology a solid-gold bit of IP if it can solve the problem of connecting that problem and that low-cost with a stream of high-volume, high value products.

Low-cost — not “no cost”. As a friend of the Digest recently observed, “there is no free lunch, no free government and no free CO2, even though the large amounts of obesity, government and greenhouse gases we produce suggest there that there is a surfeit of all three. Actually, even CO2 is scarce where we need it (e.g. have land, water, etc.) and even when available, it is not free, even if it costs nothing, except cartage, distribution and feeding to [a microbe]. As mentioned above, $30/t is the rock-bottom for CO2 distribution for [industrial biotech], at scale for a coal-fired power plant. If there is a handy ethanol plant with production of pure CO2 that “only” needs to be compressed, piped and distributed, maybe the cost would be a little lower that $30 per ton, depending on scale.”

More about Malates

The team’s target molecule? Malic acid — one of the stars of the DOE’s Top 12 Biobased Molecules list. Malate has many direct uses and can be used in the manufacture of materials such as biodegradable plastics, fiberglass, and fabrics. But it’s been relaatively overlooked — compared, say, to the interest shown on biosuccinic acid.

The one development to date of interest had been the news from August 2012 that Novozymes announced a fungus enabling production of malic acid from renewable raw materials instead of oil.

Malic acid is used as a flavor enhancer in the food industry and can be converted into other chemical derivatives used for a variety of plastic, polymer and resin products.  Along with succinic acid and fumaric acid it belongs to the group of C4 dicarboxylic acids. C4 acids can be converted into 1.4-butanediol (BDO) that can be further converted into numerous chemicals, including plastics, polymers and resins for use in everything from golf balls and skateboard wheels to printing inks and cleaning agents. The global market for malic acid is around 60,000 tons per year with a value of $130 million and a growth rate of 4% per year. The market for BDO and derivatives is around 1.4 million tons with a value of $2.8 billion and a growth rate of 3%.

A chat with the team at Industrial Microbes

CEO Derek Greenfield and co-CSO Noah Helman joined the Digest to talk about Industrial Microbes and its prospects.

BD: Why start a company — what’s commercial in this problem?
IM: We were concerned with the cost of feedstock. We all need a more diversified base — and waste gases are going to be important.

BD: Why CO2 and methane?
IM: We need an energy source to power the transformation. What about yields? we think we can get it to 85 percent of theoretical. We don’t have to get to that to break-even — how far we go will depend on the scale, and the capital requirements.

BD: What are the main technical challenges?
IM: There are a lot of pathways and options and products, and its not immediately obvious which combinations are the best, so that’s a technical challenge, and we’ve opened the lab in Emeryville to start to do experiments.

BD: Novel pathways or known?
IM: It’s been mix and match. There are known pathways, and there are some new pathways that are poorly understood and

BD: What’s been the most interesting challenge with the oathways.
IM: These are finicky enzymes and getting pathways to work, and optimizing enzymes to work in different systems, that’s been occupying us.

BD: Host organism?
IM: We’ve not been public with that. It’s something we’re still developing, and not talking publicly about it for obvious reasons.

BD: Patent apps?
IM: We have one going through the patent app process right now., But not yet published.

BD: How’s do you rate the challenge of gas-based fermentation these days?
IM: Just doing gas based fermentation? That’s more of an engineering problem. In the
bioprocessing itself, there are knobs you can turn to get what you need — and companies have definitely been successful in growing target molecules on different gases

BD: Feedstock providers?
IM: We’ll partner with companies, and in Alberta they’ve been incredibly helpful introducing us to the community and partner with CO2 emitters.

BD: Specific sources — power companies, others?
IM: There are a lot of different options, there are very pure sources such as ethanol emissions. Then, there’s the big prize, which are flue gases from power plants. Because they are lower in CO2 and have NOX and SOX – they’re cheaper. The dirtier the gas we use, the better the price.

BD: Of the companies recognized in the Grand Challenge, only a couple of companies working on biofixation of carbon.
IM: There were three that were successful in this round, including us.

BD: What’s now going to be the focus for the new company over the next year or two?
IM: We’ll focus the rest of the year on developing the technology. The Grand Challenge grant will last us for two years – that’s the runway we need. For the 6-9 months its a real period of getting our hands dirty in the lab, round out the IP.

BD: The next big milestone?
IM: When we have a handful of malic acid, made from two greenhouse gases.

BD: How long until then?
IM: Our guess is maybe 18 months.

BD: How is it to find yourself in start-up after the years at LS9?
IM: We’ve talked about it. It’s both exciting and terrifying. All these things you take for granted, now suddenly you have to do for yourself. Looking back, we didn’t appreciate all the infrastructure at a company like LS9 as much as we do now. You try and recreate that at a small company, but it’s not the same as having it provided for you.

BD: What do you miss the most, being now at a small company?
IM: The team. Talking problems through with a larger group.

BD: What’s it like being in Emeryville, in the center of the universe?
IM: Amazing, there are like five companies in our one building. We’re right across from JBEI. And I ran into this guy, working one floor above us. Six or seven years ago he was a high school intern working with us in one of the labs. Now, you hardly recognize him, he’s changed so much, and the space is changed so much. It’s been good to see.

You can learn more about Industrial Microbes via their website, here.