Plug-and play synthbio: Arzeda, INVISTA, others finding new pathways to affordable, everyday materials

January 17, 2016 |

BD-TS-011816-appstore-smA new generation of advanced technologies, based primarily in the United States but active in Europe and around the world, is changing our way of thinking about what a factory has to look like, one that produces the materials of everyday life — clothing, foods, vehicles, buildings, roads and devices. The big chemical vat is being slowly but irreversibly supplanted by microbes so small that you couldn’t see a thousand of them laid end to end, with the naked eye.

Along the way they are changing our ideas of inputs. Once, most chemicals were made from mined ingredients, then along came coal-based chemistry. Then, a few generations ago came petroleum-based technologies. Today, increasingly we look to waste carbons and low-cost sugars .

As we observed last week in the Digest, in “E Pluribus Unum”:

A new trend in the story of synthetic biology: the migration from the old “hardware” oil and grain refinery model to a model based on apps. In this case, proven, trained-up microbes that can each produce a target molecule from waste carbon. Shifts in worldwide demand? Pull out the old bug, swap in the new.

As LanzaTech CEO Jennifer Holmgren remarks, “Since it is biology and the reactor doesn’t change, the production of new chemicals can be done with a flick of a bug…  produce ethanol today, butadiene pricing goes up, no need to put more steel in the ground, flick the butadiene bug in for a campaign and produce butadiene while the price is still high.  So you aren’t 2 years behind a cycle.  I think of it as hardware, software.  You’ve installed the hardware now just add a new version of the software or a different app.”

Further evidence piled up this week with news from the US Patent & Trademark Office that the US has granted INVISTA a patent for engineered polypeptides and their related crystal structure details, which are both useful for producing bio-derived compounds such as butadiene and isoprene. INVISTA collaborated with Arzeda to develop the innovations covered by the patent.

INVISTA’s interest

The summer before last, INVISTA, owner of the LYCRA brand, introduced the first commercial offering of a bio-derived spandex — the stretchy fabric commonly found in swimwear, sportswear and dancewear. The company says approximately 70 percent by weight of the new LYCRA bio-derived spandex fiber comes from a renewable source made from dextrose, derived from corn. The use of a renewable feedstock in the making of this new LYCRA bio-derived fiber results in a lower CO2 emissions footprint than spandex produced using traditional raw materials.

INVISTA, which also produces the COOLMAX, CORDURA, STAINMASTER, ANTRON, THERMOCOOL and THERMOLITE brands, said at the time the new fiber would provide retailers and manufacturers of stretch fabrics a spandex fiber option that can impact the overall lifecycle analysis of the fabric and garment, and should not require re-engineering of fabrics, finishing processes or garment patterns.

Flick in, er, what bug? The birth of novel pathways.

So, if the model is moving from “big vats generating large-scale, low-cost volumes of known chemicals” to a hardware/software model — um, who’s minding the App Store?

That’s where companies like Arzeda come in — specializing in developing novel “pathways”, which is to say, a prized material that the magic bug didn’t know how to make before.

Take for example butadiene. It’s a material you find in rubber, spandex — things that are stretchy but long-lasting (after all, bubblegum stretches and plutonium lasts forever, but finding materials that are functional, durable and affordable, that’s the perplexing part).

For many years, we have made butadiene affordably because of an accident of the way we make other fuels and chemicals. As everyone knows, we refine globally a colossal amount of petroleum every day. Some of that is refined into something called naphtha, which has been used for eons to make ethylene (which you might know better as Glad Wrap, which is polyethylene). It’s the world’s most-produced chemical, a building block of immense importance. Extra naphtha was used to make butadiene.

But there’s another way to make ethylene, and that’s by steam-cracking ethane, which is a major component in natural gas. As you have likely read, the US is in a natural gas production boom, and prices are low compared to petroleum (though that’s evened up more in the past year with falling oil prices).

Result? Large petrochemical players are building ethane crackers to make ethylene. Leaving us a world somewhat short on naphtha. And as it turns out, it’s a real nasty piece of expensive chemistry to make butadiene from ethane. So, butadiene prices have been rising.

Enter, the magic bug

Now, here’s the problem. Everyday, off-the-shelf organisms of the type that live all around us know how to do many things well. There are pathways to make sophisticated materials like hair, teeth, spider silk, clamshells, you name it. But they don’t make butadiene.

So, enter companies like Arzeda, which was formed as a computational biology spin-out from the University of Washington and uses its tech to engineer fermentation strains that meet cost, performance and sustainability goals based on target molecules that are difficult or impossible from oil feedstock.

So, they are in the business of making novel pathways and novel enzymes. Which, when successful, give you feedstock flexibility, and get us away from the “all eggs, one basket” approach that we have been using since the beginning of the Industrial Revolution, with the resulting commodity price swings as demand, supply, technology and discovery rotate in what Douglas Hofstader once described as “an enternal golden braid.”

Others in the field?

It’s what Genomatica does, in many ways, though it generally works up its own molecules (something that Arzeda does too). LanzaTech has been active at it. Smaller companies like Industrial Microbes, TerraVerdae BioWorks and Mango Materials have been hard at work on, too.

And this past week, Amyris announced the availability of its Pathways Program, opening up its advanced technology platform and leading capabilities to researchers and companies wishing to determine the viability of biological production of target molecules at a lower cost and with minimized risk. Through the Pathways Program, partners can, with a small initial investment, sponsor and secure a molecule they are interested in having Amyris produce using the next-generation tools and technologies being developed through the company’s recently announced technology investment agreement with the Defense Advanced Research Projects Agency (DARPA).

Reaction from INVISTA, Arzeda

“The work detailed in this patent provides innovative solutions to potentially increase the global supply of bio-derived chemicals,” said Bill Greenfield, president of INVISTA’s Intermediates business. “This patent is an example of INVISTA’s biotechnology research capabilities working together with Arzeda and demonstrates our commitment to developing new bio-derived processes for a range of products.”

Arzeda CEO Alex Zanghellini added, “The issuance of this patent is yet another example of the power of combining Arzeda’s computational protein design technology Archytas with experimental screening to rapidly design synthetic enzymes. With INVISTA’s expertise in biotechnology and industrial scale-up, we are confident this collaboration will lead to advanced bio-processes for the production of more sustainable industrial chemicals.”

The imperative: Colloborate

There’s the scoping out of pathways, the engineering of microbes. Then there’s the entire field of optimizing strains for rate, titer and yield performance at industrial scale. Not to mention the field of developing increased tolerance to target molecules in the fermentation broth, separations technology, and the field of improving the longevity and recoverability of biocatalysts.And, there testing at pilot scale. Just to mention a handful of the essential technical areas in R&D.

So, the smart companies collaborate. Not just because they have a target today. Also, because they like to have deep hooks into advanced technologies in case a target turns up tomorrow. Or, say, should a competitor make a material advance.

Another reason to collaborate? Frankly, a lot of the techniques are tied up in the IP of companies like Arzeda, Genmatica et al. You couldn’t do some of this stuff without partnering, without a gigantic effort to find novel ways to accomplish the same ends, thereby avoiding IP disputes and the lovely halls of the Robert F. Beckham Federal Building in San Jose or the US District Court Buiding in Wilmington, where many of these disputes end up in legal wrassling.

“The IP landscape may not be free. In our case, we have strong technology IP and partners can’t always access this without collaboration,” said Zanghellini.

Isn’t sugar unaffordable?

Well, depends on the target. Right now, making fuels from conventional sugars is a no-go — oil’s too low, sugar’s too high. It’s that Eternal Golden Braid, you see — an argument over petroleum market share is creating a supply overhang and a resulting price barrier for some high-performing renewable fuels.

Same goes for bulk chemicals that go for less than $1/pound. But when you get to speciality chemicals that are priced int he $10-$20 range per pound, the economics of sugar are less important that the economics of the process.

That’s where biology comes in. You see, the promise of biology is one-pot production of target molecules. In the world of petrochemicals, the steps to make some chemicals begins to sound somewhat like a verse out of the old spiritual song, Dem Bones:

Thigh bone connected from the knee bone
Knee bone connected from the shin bone
Shin bone connected from the ankle bone
Ankle bone connected from the heel bone

That’s because, in petrochemical refining, each step requires a pot.  In the case of microbial factories, there are lots of steps but they all take place inside or around the same cell.

So, to use an everyday example, we make fingernails, bile and muscular energy from the one set of inputs (i.e. food, oxygen, water and sunshine) in our own bodies, and cells that produce a target material can produce the whole thing — from the initial sugars, air, water, fats and oils that we take in. Just different cells located in different areas that specialize in different materials. The brain is in charge of dialing up the apps and setting production targets.

Why now, why not before?

If you look at the DOE’s list of top candidates for biobased molecules, you might see that we have made great strides on some, like succinic acid — less so on others. Why?

What experts tell the Digest is that it comes down to maturing technology. While some of the molecules there definitely have good building block characteristics — for example,  chemical functionalization and more oxygen — in a lot of cases the technology hasn’t been ready.

Take for example levulinic acid, which GF Biochemicals has been hard at work on. Until recently, the chemical conversion from sugars pathways wasn’t workable — the economics around the existing, known pathways was not good enough. Succinic was an example of an earlier success story, in some ways because succinic is a “very obvious part of the pathway,” as Arzeda CEO Alex Zanghellini explained to the Digest. “If you look at some of the other molecules, the ability to ferment typically has to be built from scratch.”

Where next?

So, we understand why larger companies are partnering to access the techniques developed by smaller companies like Arzeda and Amyris. Where will it take us?

In a word, diversification.

Right now, we’re in the Golden Days of the Apps. That is, more ways to make stuff. To an extent, we are seeing lots of new industrial capacity emerge. And that means more places to make stuff. Ultimately, we’ll see more technologies reaching into waste carbon. Which is to say, more things to make stuff from.

Have to have all three. You can’t get world scale, even with an app and fermenters, if you don;t expand the feedstock supply because prices will simply go up and eventually the process is unaffordable. And there’s not much point in having a great App and a terrific feedstock if there’s no nearby production capacity, because transporting feedstock over long distances is a killer to process economics, especially with biomass.

And there’s no point in having a transformative feedstock and nearby production capacity, if you don’t have the App.

So, it’s the death of “same-old, me-too” and that’s exciting — that re-thinking of the eternal golden braid that is helping us put more factories, making useful materials for a growing population, on the head of a pin than perhaps even angels can fit in there.

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