Beat the Heat – Novozymes breaks through again on ethanol yield; yet, are organisms telling us to cool it?

September 20, 2021 |

As has been reported out of the Fuel Ethanol Workshops, Novozymes has introduced two advanced technologies, in yeast and fiber, of material significance in the here and now of ethanol, but also in how and how far optimization strategies can and will take us down the road in the broader world of fermentation science. So let us explore that in some detail today.

First, the news. Innova Element is the latest addition to Novozymes’ ambitious Innova yeast platform that was launched less than three years ago and has met a clear need for better performance and reliability. Element specifically targets ethanol plants seeking the highest level of starch and glucose conversion.

And, just a few months after establishing a fiber platform, Novozymes introduced Fiberex F2.5 – continuing to advance its fiber-degrading technology based on full-scale plant trial results and fiber analysis. For plants seeking to access lower carbon fuel markets for diversification, Fiberex F2.5 unlocks next-generation biofuel production while expanding plant profitability.

The holistic approach

“By adopting a holistic approach in developing technology platforms, broad biotechnology toolsets, and consistently launching breakthrough solutions, we aim to maximize opportunities for bioenergy producers,” Brian Brazeau commented — he’s Novozymes’ President for North America and Vice President, Agricultural & Industrial Biosolutions, Americas, and frequently in the news around Digestville. 

“The launches of Innova Element advanced yeast, Fortiva Hemi, our newest liquefaction solution, and Fiberex F2.5 for fiber-to-low-carbon ethanol production, together deliver the most holistic, sustainable, and advanced approach to ethanol production.”

Holistic, advanced. But something more than that. As I have often read in Proverbs, is there not a case here that “iron sharpeneth iron; so a man sharpeneth the countenance of his friend”? It is not just a case of the three Musketeers of Element, Fortiva, Fiberex — there’s a learning taking place under the chassis of Novozymes that is powering all of these advances. 

And, it is not without note that other companies are furiously innovating — consider, for example, the Lallemand advanced yeast that started the Yeast Wars. Leaf’s been at it hammer and tongs, too. Iron sharpeneth iron.

The Element key takeaways

  • Increases ethanol yield by 2% on average. Operates in a wide variety of fermentation times and excels in fermentations greater than 54 hours.
  • Innova Element is a drop-in solution that converts most sugar to ethanol compared to all other yeasts, enhancing the profitability of ethanol production.
  • Powers through high temperature excursions without sacrificing yield. It can achieve higher yields during fermentation temperature excursions, up to 36⁰C/98⁰F, reducing variability and process upsets.
  • Enables producers to expand throughput by fermenting high dry solids. Developed to withstand the rigor of heavy-duty, hard-running plants, Innova Element can ferment up to 36% of dry solids, while tolerating high ethanol titers (>15% w/v) in fermentation.

The Fiberex key takeaways 

  • Access low-carbon fuel markets with Fiberex F2.5; on average 3% of total ethanol production qualifies as cellulosic ethanol for low-carbon fuel markets*.
  • F2.5 enhances corn oil recovery, unlocking up to 15% more corn oil yield from the fiber matrix, enabling it to be used for animal feed or sustainable biodiesel production.
  • Reduces residual starch by 18% to gain further performance on ethanol generation.
  • At more than one third lower dose than competitive products currently on the market, Novozymes provides concentrated enzymatic activity for the most efficient corn fiber conversion today.

The War on Yield

The headlines scream yield, but decarbonization is not taking a back seat, Any advances in yield make advances in decarbonizing – more ethanol to amortize against the inputs. Novozymes is pursuing both on yield and carbon intensity, break-neck. As Brian Brazeau noted to The Digest, decarb is not in the back seat. “we put a real focus on [carbon intensity]. we have our customers and partners looking for it.. We definitely see decarbonization as part of the future, there are more and more stories about it and there is the intersection with infrastructure investment in the US and announcements on carbon in Europe. 

“Even the progress with electrics tells us that decarbonizing transport is a major priority. We believe that people have seen seen more and more benefits of using ethanol, and the lower carbon intensity scores are helping with that.  We are transitioning from a conversation about perfect 1-2 years ago, now it is more and more a search for good.”

But there’s more than fuel here. “I think there’s going to be a day we look back at the ethanol industry, and see that it was the scaling of a true industrial bioprocess and [the birth of] biorefineries,” Brazeau predicted. 

What’s it all about?

This is a 5th strain, and raises the bar. With each successive launch within Innova, Novozymes has been pushing the boundaries — especially, pressing on yield while maintaining the robustness. The bottom line in fermentation with yieldophiles is that designing thoroughbred strains, they get more stressed, the tendency is to break down more easily. Classical breeding and very specific strain engineering is taking place to make this assault on yield without creating an organism that shines in the lab and collapses in the field.

But let’s spend a moment on that 2 percent push on yield. At industrial scale, that’s huge, that’s Everest-without-supplemental-oxygen performance.

From TRY to TRYST: what are we learning from industrials about optimization

In industrial fermentation, pharma is the 100 meter dash: limited, precise, an explosion. Industrial biotechnology is the Marathon, damnably long, damnably hard. The science moves fast, the competition is hot, the barriers to innovation are steep and the field is crowded. 

In pharma, time is of the essence, there are no 10-year yield optimization programs before  launching COVID-19 vaccines.  “Titer, rate, yield’ (TRY) is a mantra for all fermentation sciences, but in the world of pharma, it’s also a  case of having no Gods before Performance and Purity. 

The scale and timelines in industrials are, well, a case of ‘And, now for something completely different.” Let’s put it in perspective with a thought experiment.

I want you to picture the Moderna or Pfizer COVID-19 vaccine, picture the volume of it, the liquid that is delivered into your arm. Now, double it, to account for a second dose. 

Now, multiply it by 7.5 billion so that everyone on Earth over the age of, say, 12, receives a vaccine. Picture that vast volume of product, that ocean of vaccine, in one big giant vat.

Now, let’s turn to industrials, specifically liquids for fuel, power and chemicals. How long would that same enormous vat you have imagined, keep Earth’s industrial society going, the lights burning, the vehicles running, the products on the shelves at the stores?

About 32 seconds, that’s how long.

And that’s why 2 percent improvements matter at the scale of industrials, and why industrial fermentation is the place where the Grand Battle for Scale and Optimization occurs.  The optimization going on in industrials is elite on elite, team inspiring team, company inspiring company, iron sharpening iron, diamond etching diamond. It’s never been seen before.

We know it from fever and work. When we have fever, it is our own microbial system responding to a foreign invader, and the more work they do, the more heat they produce. Like the elite marathon runners, if we do too much work, the core temperature climbs too high, and the runner collapses. So it is with microbes.

Of all the challenges than microbes face when operating at industrial scale — too much alcohol in the broth, too many side-reactions, too many infections, too much clock getting burned — perhaps the ultimate challenge is heat. We have engineered our organisms as extremophiles — but ultimately all organisms falter, break down, die when the heat’s turned up. It is not a question of whether, but when.

We may find that organisms are telling us something about heat, and what to do about it — even in their mute way, they may be speaking to us. Though it is something that is not so much expressed in the realm of genetics, which is generally speaking, in mathematical terms, part of the world of number theory and analysis, and to look instead at geometry and topology.

I’m not crazy. The traditional gulf between geometry and number theory is closing, fast. Consider this excellent summary from Quanta magazine on recent, astounding progress on the 54-year old Langlands program to find a “geometric object that encoded answers to questions in number theory.” More about that here.

We’ll leave the convergence of numbers and shapes for now and return to the realm of organisms, except to note that the solution to the conjectured Langlands correspondence could help solve the problem of the Riemann hypothesis, which is one of the handful on the list of million-dollar Millennium Prize challenges. 

I mention that entree to a note on Riemann surfaces. You probably haven’t heard of these, and you’ll be bored to death if I mention that they have something to do with geometric models known as manifolds, but your ears might prick up if I mention they have quite a lot to do, at a foundational level, with the General Theory of Relativity. Riemann surfaces might be all around you. 

Topology and performance

We’ll leave the mathematics of General Relativity, for another day, so that we can visit with a diagram of what are called Ricci flows, which is part of the science of the diffusion of heat.

See, we were talking about heat all the time, it just seemed we were out there in a kooky branch of geometry which had no bearing on organisms and stress.

Here is this diagram of several stages of Ricci flow on a two-dimensional manifold.

It’s interesting, but even more so if we show you a picture of sacchoromyces cerevisiae, the beautiful and ancient workhorse of enzymes, friend of glucose, pal of ethanol, the fellow who put the rise in your bread.

For now, note that these are spheroids and they have these strange buds on them, buds that will become (down the line) new yeast, what you’re seeing is the mother-daughter yeast, still connected. Here’s a diagram of budding from the Colins Lab at Cornell University, here.

And, yeast come in different shapes — here’s a picture of yeast from the Max Plank Institute, here. Put it together and you’ll see quite a bit of correspondence between yeast and the math of Ricci flows. Spheroids, rods, half-domes. 

So, let’s take another step forward. Here’s an image which sums up the evolution of yeast nicely. Here are the spheroids, there are the rods, and there are rods breaking apart in the classical division of yeast.

Only, this isn’t an image or a diagram of yeast, at all.  I was showing you something at the other end of Nature’s scale. This is actually a sketch of “the mechanism of binary star formation given an instability of the Jacobi sequence”. 

And yes, star formation is all about heat — when gravity brings enough mass under enough pressure, heat rises, fusion begins. 

What does it produce? For one, these spheroids, rods and teardrop shapes. 

What is Nature telling us about this topology flow, which we see deeply conserved by microorganisms?

Let’s consider another example, if binary star formation and or Ricci flows are not your brand of candy. Let’s consider the humble raindrop.

Or, rather, raindrops. They are a product of heat and part of Nature’s scheme to diffuse heat — through the steam-cloud-rain cycle. Our friendly raindrop takes a series of shapes in its brief lifecycle, and as it responds to the hostile conditions that weather presents to them. Here’s a diagram from NASA.

Spheroids, half-domes, rods and teardrop shapes, and a splitting pattern that looks an awful lot like micro-organisms.

What about some other classic shapes in the world of industrial biotechnology and the world of genetics. Consider, for example, the helix. Well-known is the famed double helix of DNA, and you may be familiar with the single helix of RNA. 

What we don’t know very well — because topology tends to be outside the realm of scientific investigation in genetics, is precisely and exactly why DNA and RNA occur in a helix-based structure.

Some answers may lie in heat transfer. Scientists suggest that heat raises the amount of kinetic energy that is available to living things, and can power a faster metabolic rate; metabolism scales with temperature as we see discussed here, And, speed can be advantaged in evolution (ask any cheetah). Why wouldn’t it be the case that the helix developed to help transfer heat?

A mundane example? Consider the Lummus Technology heat transfer technology, HELIXCHANGER. As is said of it “Quadrant shaped baffle plates are placed at an angle to the tube axis in a sequential arrangement to create a helical flow pattern.” What’s the advantage? Helical designs, says Lummus, increase the amount of surface area in contact with the substance to be heated or cooled. 

Bringing it all together

Heat, it may be that organisms are telling us what their limits are, that heat stress is a serious barrier to enhanced performance, and that solutions in heat may lie in something more than knocking out this gene or that to modulate stress response, and so forth. It may lie in study, rather, of the genetics of topology.

Yes, we are familiar with the double helix, but mostly what we think about is the A,C,G.T, and not the S,H,A,P,E.

What about something a little different? This is a helicoid, not a double helix.

Helicoids are in many ways a better way to think about DNA and RNA than the helix.

For one, it is three-dimensional object just as proteins are — a helix is really a description of a line of zero-width. The nature of the spiral, the sweeping space which the shape commands — that’s where DNA lives. 

For our purposes today, let’s also note the similarities to Riemann’s minimal surface, objects with interesting mathematical simplicity and highly extensible. Here we have a shape that biology uses, that life likes.

What’s the importance of a minimal surface and how does it relate back to biology, exactly?

Wikipedia notes: “Minimal surfaces have become an area of intense scientific study, especially in the areas of molecular engineering and materials science, due to their anticipated applications in self-assembly of complex materials. The endoplasmic reticulum, an important structure in cell biology, is proposed to be under evolutionary pressure to conform to a nontrivial minimal surface.”  What’s the endoplasmic reticulum? Again, Wikipedia: “in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding.”

Over the aeons and across the spectrum, shapes that microbes and proteins use are deeply conserved in Nature — that is, we see them everywhere. In the world of proteins, shape determines activity, activity determines function. There are plenty of signals from the organism that they are fundamentally organized in shapes around the transfer of heat and that heat is the ultimate problem. 

It’s in the heat equation that we find the basis of quantum mechanics (via the Schrodinger equation), and we use Ricci flow in heat diffusion, and in heat exchangers.  

We see it at the macro-scale, we see it at the micro-scale. It may be that our ultimate journey in strain engineering will be to deal with the heat.

And that may be where the iron needs most to sharpen iron.

Category: Top Stories

Thank you for visting the Digest.