In search of renewable butadiene: Genomatica, Braskem hit key milestone

Geno-Braskem-112415-smButadiene is beginning to emerge from the Braskem Genomatica collaboration.

But could it be that the real significance lies not in progress with butadiene, but in Big Data itself, the harnessing of complex mathematics to make products that are possible, but not currently produced, in Nature.

News has arrived from California and Brazil that Braskem and Genomatica have been producing renewable butadiene in a one-pot process at lab-scale since the beginning of the summer.

And when you think about butadiene, think tires.

As in the mountains of rubber tires that pile up in landfills around the world each year, made from fossil hydrocarbons — whether you are driving an ICU engine, or a spiffy electric car, or taking Uber or even using a bicycle to get to work. Tires are not the only product made from butadiene — but the urgency of making a renewable tire, using the tools of biology and renewable resources — well, it ought to be on minds around the world, especially as transportation growth continues to be a story in the developing world.

Butadiene is a raw material used as well as for electrical appliances, footwear, plastics, asphalt, building materials, and latex. The demand for butadiene is over 20 billion pounds per year worldwide, and growing.

A Big Story in Big Data

But the urgency of reducing our carbon footprint, irrespective of the engine we use for our vehicle, is not the most compelling facet of this Braskem-Genomatica story. Something that will travel even farther down the road for us, as a civilization, and present in this story is the application of computation mathematics and biology. Which is to say, in the popular vernacular, the convergence of Big Data and Big Bio — to make better products, faster, exploring the manufacturing potential for useful materials to be found in the billion-year-old metabolic pathways in the life itself, or the potential pathways therein.

For those new to the jargon, a metabolic pathway is nature’s series of steps of converting simple building blocks such as water, oxygen and sugar into the myriad bath of chemicals that provide our physical structure and maintain it. At every step, our genes code to make certain enzymes that stimulate certain activities — resulting in everything from bones, muscles and nerves to the fluids that maintain and repair them, and power up and link all the organs that run the body in all its activities.

All life has metabolic pathways — but think of it like a pile of LEGO bricks. The box might suggest that you can build a space shuttle from the parts inside, and will guide you step by step in how to  make it, but you can use the same parts to make other things by assembling them in different orders and ways.

It takes a gigantic amount of highly concentrated and well-designed computational power to figure out the 60 or so possible metabolic pathways which you could assemble from life’s library of known enzymes and activities to make butadiene from sugar. And it takes another massive computational effort to rank those for degree of difficulty and potential yield and figure out the five or so which a biological and engineering team might embark upon developing as a solution to the problem of renewable butadiene.

That perhaps explains the “genome” and the “automatica” that were crashed together in a head-on collision between two perfectly unacquainted words in the English language to create “Genomatica”.

We generally experience Genomatica. as a company, in terms of the products they develop specific affordable, at-scale, renewable solutions for: butanediol (BDO), the afore-mentioned butadiene, and more recently they have announced progress on renewable nylon. But at its heart, the company is a big giant library of life built on top of a colossal computing machine. As if the Tree of Life were growing out of a Babbage Differential Engine.

One day, we may broadly come to see as a society that the internet, our biological system and transportation systems all have the fundamental attribute of networks — and we may see metabolic pathways, to put it one way, as Nature’s way of stopping a process traveling in a car and transferring it to a train. Where transportation pathways change the “where”, metabolic pathways change the “what”, but pathways they are, subject to the mathematics and diffusion of complex networks.

But let’s take a moment also to reflect upon pathways that involve organic activities that all have a foundation in nature, but are not necessarily found in nature today. Simply put, Nature hasn’t thought up a compelling reason to actually develop an everyday pathway from sugars to butadiene. Clearly, no one has fully acquainted Mother Nature with the financial opportunities available in making Air Jordans that simply grow on your feet after eating a meal.

It sounds weird but there’s actually no compelling genetic reason that we couldn’t grow and shed footwear, as we grow and shed fingernails and skin.

Here’s how it works

“The way the platform works,” explains Genomatica’s Nelson Barton, “we start with all the many different ways to get from sugars to butadiene, and then start narrowing those down, which pathways with the favorable energetics and which don’t. Which have steps that are known in the literature where an enzyme can work on the substrates in the pathway. Many of the enzymes not working on their native substrate, so we look at which ones have favorable characteristics — for specificity and rate. In cases we have to do engineering, but in every case where you have a substrate switch, we aren’t going to get 100% of that enzyme’s natural activity, so we run a whole bunch of factors to predict how well can they make butadiene.”

“From that we end up selecting the pathway we’ll go forward to building out a functioning strain — and in our case, we greatly broadened the gene pipelines, and through metagenomic analysis and environmental work we produced libraries and with next-gen sequencing, now we have more than a dozen icandidates in this class.

“But it is more than simply finding some gene and overexpressing it.  Our invention has to work well as a pathway, where there is sharing of co-factors, and each step impacts everything else down the line, so we look for internal co-optimization. And, as we produce the strain we are working closely with process design.”

That’s important, because it is just not effective to design a great strain and hand it off to process design that has to deal with any real-world troubles which aren’t encountered in the pristine lab. Process and design work together, even at this microbial scale and this early stage.

Which is why you’ll find Braskem team members embedded at Genomatica headquarters in San Diego.

Which brings us back to butadiene and tires, and much more. You see, this isn’t Branskem’s first rodeo. It’s part of an effort, since the company’s origin in 2002, to invest in technological processes that result in greater efficiency and sustainability of its products. In addition to the project with Genomatica, Braskem has been producing polyethylene from ethanol since 2010, labeled as ‘I’m green’, and has another cooperative agreement with partners to develop green isoprene.

“We’re delighted to share this strong technical progress,” said Patrick Teyssonneyre, Innovation and Technology Director, Braskem. “This sets a foundation for an important new process for the industry. The work we are doing with Genomatica is another example of the success of our open innovation system, which aims to provide our customers with competitive advantages in their businesses. We believe that renewable chemistry is an important part of their future and ours.”

Three takeaways from the news this week.

1) Direct, continuous production: The program team has successfully developed a microorganism that consumes sugar and converts it to butadiene at lab scale, in two-liter fermenters. Butadiene has been produced, collected and measured continuously, over the course of multiple days for each fermentation.

2) Development of multiple direct pathways and novel enzymes: To develop an optimal process, Genomatica used its computational tools to figure out every possible way that a microorganism could theoretically make butadiene, and identified 60 potential biological pathways. The five best were selected for experimental validation, conducted by Genomatica and Braskem teams in San Diego and Campinas, along with full-time visiting scientists from Braskem at Genomatica’s Innovation Center. The team explored a large number of enzyme candidates, applying environmental sampling and metagenomics, for each step in the potential pathways. Genomatica then multiplied enzyme activity 60-fold on non-native substrates using its high-throughput screening and enzyme engineering capabilities.

3) More intellectual property: The program team has significantly added to the extensive intellectual property that Braskem and Genomatica have in this field. This work speaks to design of optimal microorganisms and processes; supports subsequent development stages; and represents an important competitive advantage.

The bottom line

Just like genomics, human life and scientific innovation has design and expression, too. So the innovations you’re reading about today will ultimately be expressed in tires, electrical appliances, footwear, plastics, asphalt, building materials, and latex.

You might even see them in LEGO bricks. LEGO has announced a $150M effort to replace fossil sources of ABS for its iconic plastic bricks. ABS — that’s acrylonitrile butadiene styrene, so you wouldn’t be wrong to see potential for renewable LEGOs in all of this.

One day we’ll see the first truly renewable computer — biobased networks and biobased materials running all our computations, which ultimately as materials would owe their origins to water, sugar, oxygen and carbon dioxide and the pathways of biology itself. Read more on that here. and here m and here.

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