X-Crobes: Kuraray invests in Amyris, what’s next for synth-bio and performance molecules?

April 1, 2014 |

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There are microbes and X-Crobes.

The former: what you find in nature.

The latter: strange beings from the Digest Multiverse. Poly-performing platform organisms endowed by synthetic biology with Xtraordinary properties.

The X-Crobes are back in the spotlight this week with news that Kuraray is investing in Amyris. Here’s what’s up, and why.

In California, Amyris and Kuraray announced the expansion and extension of their ongoing collaboration in high performance polymers using Biofene, Amyris’s brand of renewable farnesene.

Amyris and Kuraray launched the collaboration in 2011 with an initial focus on using Biofene-based polymers to replace petroleum-derived feedstocks in tires. During this time, Kuraray developed Biofene-based liquid rubber that reacts with tire rubber more easily than traditional materials and strengthens adhesion of rubber components to improve tire shape, stability, and performance.

What’s that? A mere performance polymer made from modified yeast, you say?

No, it’s an X-Crobe unveiling its microscopic superpowers.

Disguised as ordinary companies, Amyris and Kuraray extended the duration of the research and development portion of their collaboration for at least two more years. The parties also reaffirmed their commercialization goals by expanding types of, and fields of use for, Kuraray polymer products containing Biofene.

As detailed in the agreement, Amyris will receive an undisclosed amount of collaboration funding over the next two years, and Kuraray will purchase approximately $4 million of Amyris’s common stock in April of this year.

Of benefit to Earthlings

Back in August 2011, Amyris announced the initial collaboration agreement with Kuraray to use Amyris Biofene to replace petroleum-derived feedstock such as butadiene and isoprene in the production of specified classes of high-performing polymers.

Upon successful completion of the technical development program for the first polymer, Amyris and Kuraray said at the time that they would enter into a supply agreement for Kuraray’s exclusive use of Biofene in the manufacturing and commercialization of these polymer products.

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What is butadiene, again?

Butadiene is a chemical building block used to manufacture synthetic rubber, nylon, latices, ABS plastics and other polymers.

Results from the first collaboration agreement

Today, according to the partners, “leading tire manufacturers are conducting field, safety and performance tests of Kuraray’s Biofene-based liquid rubber in their tire formulations with a number of these tests nearing conclusion.”

Also, during this period, Kuraray produced and began customer sampling and product evaluation for a new category of elastomers, Hydrogenated Styrenic Farnesene Copolymer (HSFC), which have shown to have improved flow properties and low residual strain, opening opportunities for vibration dampening product applications.

Remember 2011 and the spike in butadiene prices?

The summer of 2011 was an important watershed moment in the development of this sector. Though the Renewable Fuel Standard was just underway and strong investment was continuing in the fuels sector — when spot prices of butadiene spiked to $3/kg by July — triple the price of fuels — the writing was on the wall as far as the direction of so many of the advanced companies.

Though the markets were smaller in high performance polymers than in fuels, there was more than just an opportunity to chase higher margins: there would be a steady supply of strategic investors and partners looking for ways around $3000/tonne raw materials, and around the price volatility.

Future options in platform development

amyrisyeastdiagram

For those following Amyris as a synthetic biology company, for its achievement in training yeast to produce biofene in commercially viable quantities, here’s some news worth noting.

Last week in New York, researchers at New York University have created the first ever yeast chromosome using synthetic biology. The new yeast cell, that was created by replacing original chromosomes with synthetic ones, was observed to reproduce. More than 50,000 changes were made to the DNA and researchers can now more easily manipulate the yeast to do what they want, including potentially making better biofuels.

Over the last five years, scientists have built bacterial chromosomes and viral DNA, but this is the first report of an entire eukaryotic chromosome, the threadlike structure that carries genes in the nucleus of all plant and animal cells, built from scratch.

“It is the most extensively altered chromosome ever built,” said team leader Dr. Jef Boeke, a pioneer in synthetic biology who recently joined NYU Langone from Johns Hopkins University. “But the milestone that really counts is integrating it into a living brewer’s yeast cell (Saccharomyces cerevisiae). We have shown that yeast cells carrying this synthetic chromosome are remarkably normal, only they now possess new capabilities and can do things that wild yeast cannot.”

The team was able to manipulate large sections of yeast DNA without compromising chromosomal viability and function using a so-called scrambling technique that allowed the scientists to shuffle genes like a deck of cards, where each gene is a card. “We can pull together any group of cards, shuffle the order and make millions and millions of different decks, all in one small tube of yeast,” Dr. Boeke says. “Now that we can shuffle the genomic deck, it will allow us to ask, can we make a deck of cards with a better hand for making yeast survive under any of a multitude of conditions, such as tolerating higher alcohol levels.”

What does that mean?

Using the scrambling technique, researchers say they will be able to more quickly develop synthetic strains of yeast that could be used in the manufacture of rare medicines, such as artemisinin for malaria, or in the production of certain vaccines, including the vaccine for hepatitis B, which is derived from yeast. Synthetic yeast, they say, could also be used to bolster development of more efficient biofuels, such as alcohol, butanol, and biodiesel.

Their initial success rebuilding a functioning chromosome will likely lead to the construction of other yeast chromosomes (yeast has a total of 16 chromosomes, compared to humans’ 23 pairs), and move genetic research one step closer to constructing the organism’s entire functioning genome, says Dr. Boeke.

Future directions for butadiene: volatility, growth continues

The Argus DeWitt Butadiene Annual reports that “the global butadiene market has seen an unusual amount of volatility over the last year.”

This report indicates that while some supply issues are being addressed by the addition of new capacity in Europe and Asia-Pacific, demand growth in Asia-Pacific is not keeping up with capacity expansion for butadiene and major derivatives, thereby putting pressure on global market prices.” Specifically, the report indicated that “US importers will find more butadiene on the market but less C4s,” as a result of new butadiene capacity that will come on line in Europe in 2014 and 2015,” and that “China will continue to be the world’s largest butadiene consumer with, demand growing at 5pc/yr in 2014-17.”

The report concluded that “most of the global growth in butadiene demand, especially for SBR and BR, will be in Asia-Pacific. But higher regional production may create surpluses of these derivatives at times, which may be exported to the US to support new tire plants.”

Who else is working on butadiene – exact-same or substitute?

Last November, Axens, IFP Energies nouvelles and Michelin announced the launch of a plant chemistry research partnership to develop and bring to market a process for producing bio-butadiene. They are also committed to laying the groundwork for a future bio-sourced synthetic rubber industry in France.

In April 2013, Versalis and Genomatica announced the establishment of a technology joint venture for bio-based butadiene from non-food biomass. Versalis — the chemical subsidiary of Eni — aims at being the first to license the process and build commercial plants. It will also provide over $20 million in funding to Genomatica to support development of the integrated end-to-end process.

In August 2012, LanzaTech and top nylon producer INVISTA (think Lycra and Dacron) have inked a joint development agreement to develop one-step and two-step technologies to convert industrial waste gas carbon monoxide into butadiene. Initial commercialization is expected in 2016.

In August 2011, Global Bioenergies announced a deal with Poland-based Synthos to develop a new process for the conversion of renewable resources into butadiene, involving research funding, multi-million euro development fees, royalty payments, repartition of exploitation rights, and a $2 million equity investment in Global Bioenergies.

Bringing it all together

Here’s what we have: a vital but volatile commodity — out of control, in the view of its customers. Amyris bringing forward a platform in yeast fermentation, using a modified organism, that offers an alternative with unique performance properties that improve tire shape, stability, and performance. Future developments on the horizon from the likes of LanzaTech, Global Bioenergies, Genomatica and IFP.

Players like INVISTA, Versalis, Axens, Synthos writing checks and partnering up

And — on the horizon, a technical achievement in establishing a “scrambling” capability in yeast to revolutionize the time and cost involved in developing synthetic strains of yeast to bolster development of more efficient butadiene.

When will this move from “the promise of tomorrow” to “production today”?

In the case of butadiene, based on the activity we’re seeing, think 2015 for the first commercial offtake agreements, at the latest. If nothing has come forward by then, the proposed processes have run into a lot of trouble.

For future molecules, the process will become faster. As Genomatica CEO Christophe Schilling told the Digest last year, “We are open up to the possibilities to do more, but before we start on product 3, 4, or 5, what we hope that we have demonstrated is, in terms of developing process technology, “you’ve seen what we did with BDO.” When we go forward with another product, partners can have confidence that we know what we are doing.

More to come

Look, up in the sky…

Well, maybe not quite Superman. After all, you can fit a lot of X-Crobes on the head of a pin. But, keep an eye out. If you think that technology has reached a zenith, consider potential when X-Crobes learn 3D printing. Though they may work in mysterious product lines and timelines unfamiliar to Earth-dwellers more accustomed to digging resources out of the ground and refining them — we’ll see more and more materials produced by X-Crobes — life-saving or life-extending therapeutics, chemicals, foods, fuels, and structures with extraordinary strength and flexibility.

The timelines are hardly interesting to corporations that think in quarters, or budget cycles, or regimes — but they will find a smattering of funds here and there, until the development speeds up and the vessels of production are less plagued by infections.

But these are questions of timeline rather than direction. And, in cases such as biofene, promising properties are already being discovered.

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