Talking Biotech 354 - Microalgae, factories for improved polymers, an interview with Dr. Scott Franklin === Kevin Folta: [00:00:00] Hi everybody. And welcome to this. Week's talking biotech podcast by collab. now, if you look around, it's amazing how our lives have been changed by composite materials. And we don't think about it very often, but if you look at the synthetic materials that make up everything from our car parts to your headphones, to spaceships, this stuff is everywhere. Synthetic chemistry can concoct these polymers by reacting different, smaller monomers together to form larger, more elaborate structures sometimes with really strong, uh, uh, properties and, uh, such as durability and, and all is done probably at a pretty low cost. Now biological systems also make polymers. And is it possible that with a few little tweaks that they could be genetically reprogrammed to build new structures using biotechnology. And could you use them as modern factories powered by sugar or sun [00:01:00] to make the building blocks of modern polymeric molecules? It would truly represent the next generation of material science innovations. So can we make future complex polymers from microorganisms harvested from fermentors rather than from petroleum harvested from the. today's guest thinks. So, so today's guest is Dr. Scott Franklin. He's the co-founder and chief science officer of checker spot. Welcome to Scott Franklin: the podcast, Scott. Hey, thanks, Kevin. It's a pleasure to be here today. Yeah, Kevin Folta: well, I'm really happy to have you on, I, I think it's a great opportunity to talk about this because we haven't covered this topic too much in the podcast series, and I think it's great opportunity. So let's start at the beginning. The company that you founded is working on the development of specialized compound. From biological systems. So microalgae. So what are some of the real advantages to using microalgae as a fundamental basis to develop these exciting new chemistries? Scott Franklin: Uh, yeah, I mean, the, the value in microalgae [00:02:00] as a, as a production platform for these types of molecules, is there single cell organisms. Um, so they're microbes essentially. But they, they make a lot of materials, a lot of monomers, um, that are very similar to those made by. And in fact, in many cases, the same as those made by higher plants. So when you think about many of the things. Raw materials that we derive from higher plants, um, you know, trees or crops take months or years to mature and, uh, so that we can harvest those materials. Uh, our micro oil systems, uh, typically operate on the scale of days, um, because they're a single cell organism and we've developed a lot of tools to manipulate them and change and alter. The outputs of the types of materials that they make. So you can think of them as, um, a plant like [00:03:00] platform, but they operate on a different time scale a much more rapid time scale. Kevin Folta: Okay. So I see the big advantages, but when we talk about microalgae, What exactly are they? And, you know, you've explained a little bit about why they're useful hosts, but are they specifically amenable to engineering or maybe have different capacities for different me metabolic pathways that really make them useful for this kind of Scott Franklin: application? Yeah. So if you, so a couple of points there, um, when we talk about micro alga, that's really a generic term and all it means is an alga. That's single celled. So we're not talking about things like seaweed and kelp. We're talking about single celled organisms. And usually when you think algae, you think sunlight, we don't use sunlight. There are many, many species of microalgae that actually grow under what we call heterotrophic conditions with a reduced carbon source, usually sugar. [00:04:00] So dextrose from corn or sucrose from sugar cane. And we grow these fermentation vessels. Very. Very much like we would grow ye or E coli that the attributes they have, and particularly in our case is that the strains we work with are very prolific oil producers, triglyceride oil producers. So in that respect, you can think of the starting raw material they make, uh, very akin to, uh, petroleum, uh, akin to a barrel of oil. And part of what we're doing at checker spot is exploring all the different ways we can engineer the microalgae to tailor the types of triglyceride oils they make, and also apply new chemistries to those triglyceride oils to get to new and novel high performance polymers. Kevin Folta: Okay. So here's the softball [00:05:00] question of the day. Okay. Really easy. You're using microalgae to generate specialized triglyceride molecules, different triglycerides. But what's wrong with the old way of doing this and deriving the basis for these products from petroleum or other types of synthetic chemical. Scott Franklin: So, I mean, the challenges we all know to using petroleum based feed stocks, there's, you know, really an existential crisis that the planet is facing when it comes to greenhouse gas, emissions, global warming. And these materials derived from petroleum. So I think we're definitely seeing the world move away to alternative energy sources, to replace things like coal as a fuel and a feed stock. And certainly petroleum is a feed stock. And certainly we're seeing an electrification of human transportation in the auto industry. But the global warming impacts of petroleum and petroleum products extend far beyond that [00:06:00] into chemicals. So even if we replace all the fuel that goes to automobile, transport, transport in general, to heating and cooling that we currently use petroleum derived products, floor. We have to think about replacing all of these other materials, chemicals that are derived, you know, by and large from petroleum based feed stocks. So. Microalgae and particularly sort of, um, uh, high density, fermentation systems like this offer a path to get to truly renewable, much less carbon intensive ways of making those chemical monitors that we currently use today, as well as entirely new materials. That, that we don't even have at our disposal today. Kevin Folta: Yeah. Well, there's a sort of ironic algae justice here because many of our fossil fuels are really just the remains of microalgae. [00:07:00] Scott Franklin: That's absolutely right. And that's, that's one of the reasons why these microalgae are such useful organisms for the elaboration of triglyceride oils evolutionarily. They're just inherently very, very good at it. So. Another comparison that we can make is when we compare triglycerides made in a system like microalgae and fermentation based process with traditional oil seeds. So those processes are also relatively carbon intensive due to the fertilizer requirements. For example, and land use changed. Changes that we get with cultivating certain crops like soybean, um, or fertilizer impacts of growing, um, say corn dextrose or soybeans microalgae with a sort of an, a preferred carbon source of sucrose derived from sugar cane is a very, very efficient process [00:08:00] that operates again on a really different time scale. So. If you think about a farmer who's growing say sunflowers for sunflower seed oil. Um, you know, from the time he sews his seed to the time he harvests harvests might be, you know, 90 days, for example, and he'll generate say several metric, tons of, of oil from that seed harvest per hectare. The process that we use at industrial scale. Um, in about a six day process would generate about 90 metric, tons of oil at an industrial sized, uh, fermentation, uh, vessel. That's about 620 cubic meters. And while it's true that you utilize sucrose to run that fermentation as a feed stock, the land use sufficiency of that process is much, much more favorable when we're growing. [00:09:00] Sugar and using sun sunlight to carry out that photosynthetic reaction and then converting that into sort of a high value triglyceride oil. So we actually generate more oil per hectare using a fermentation based process than we would by growing a crop. So even from a land use perspective, it's a much more efficient process. And then the final point I would say is we, we divorce. The type of oil we make from a particular geography. So what we need is sugar. And so typically you would co-locate these facilities, or we have co-locate these facilities with a source of sugar, and that could be sugar cane in Brazil. It could be sugar beets in north America or Europe, or it could be corn DROS in the Midwest. And with that process, we can make an oil that we might only find available, uh, say, um, grown in [00:10:00] the tropics. Something like, uh, cocoa butter or, um, coconut oil. We have the capability of making these types of oils in our microalgae, but completely divorced from those Kevin Folta: geographies. Yeah. But what about being completely divorced from those genetics? I mean, you already have plants that can synthesize these higher order molecules because of some. Inherent metabolic steps. So are microalgae amenable to genetic engineering. And can you essentially make it able to, uh, mimic what these higher order plants are able to do and make the Scott Franklin: structures you want? Absolutely. And that's why that's why these microalgae are such a facile platform, such a useful platform for doing this. Because evolutionarily, these micro are actually, and these micro and their biochemical processes for making triglyceride oils are actually the progenitors of those [00:11:00] processes in higher land plants in oil seeds. So they make, they actually spawned these biochemical reactions that higher land plants took on board hundreds of millions of years ago, microalgae have been utilizing these process for, you know, You know, billions of years to make these compounds and gave rise to higher land plants. So what we can do is we can actually borrow genetic information, and this is a large part of what we do genetic information from higher plant oil seeds, and we can mobilize those genetic elements in our MicroG system to elaborate new oils. That might be made in something like a coconut tree or a Palm kernel oil, or even a soy be. But even more important and more interesting is we can combine those pieces of genetic information [00:12:00] combinatorially so we can make an oil that, you know, for want of a better way to think about it is across between, uh, Palm kernel oil and high oleic sunflower oil, because we can get a certain physical property out of an oil, like. so it's really being able to combine all these elements together to create. In essence, what are new material feed stocks? Kevin Folta: But can we drill down on that a little bit more because, uh, you know, photosynthesis versus fermentation, I think about it as a plant biologist. I think of how the plants are factories. The sun is free. Carbon dioxide is free, your energy and your raw materials are there to be made into more elaborate structures. So how do the two compare photosynthesis against ferment? . Scott Franklin: Yeah. So if we're comparing microalgae and thinking about, well, Wouldn't it be more efficient to grow microalgae using sunlight. That's one aspect of your question. [00:13:00] So let's address that first. And the answer is yes, sunlight is free, but sunlight is the driving energy force in photosynthesis. Everything in organism needs to do is gonna be driven by its access to sunlight. And the challenge that you have when you start to cultivate microalgae photosynthetically and I spent a lot of time in my career doing. Um, is light limitation. As soon as that culture starts to get, um, somewhat dense and by our fermentation standards, um, that's a very, very low density. Um, the culture becomes light limited. So all the metabolism begins to slow down, which means oil accumulation slows down. Nutrient uptick slows down. So the productivity of that culture on a volumetric basis, grams of oil per liter per day becomes very, very low when we compare that with, uh, [00:14:00] fermentation based process using, and it can be the same micro species. We might be one or two log orders higher in dry cell weight accumulation. On a per day basis. So I'll give you a comparison to a facility I used to work at in Hawaii. Uh, that's still in existence today. An outfit called SciTech. They make photosynthetically, uh, grown micro Aral products. Srilina. Uh, hemato for Astra Anthem production. That's about a 90 acre facility. And, uh, when I was there in the mid nineties, we could produce maybe 350 metric, tons of spline biomas per year. Well, um, a high cell density fermentation of the micro OAL strains that we use. In a single fermentation run at 620 cubic meters, that'll produce on the order of about [00:15:00] 120 to 130 metric, tons of biomas in six days. So the productivity of these systems are just, again, their log orders different. And that, that gets you to the economics where you can start to get into producing potential replacements for petroleum derived materials. so that's, you know, that's comparing micro to micro grown in fermentation versus photo synthetically. And then the other question relates to, well, why not do this in, uh, a land plant? And that stems back to those issues of land use efficiency, and most of the oils that we want to make that are truly novel. There are no currently cultivated. Uh, agronomically important crops that elaborate those types of oil and chances are there never will be cuz the economics won't be there to do it in that way. Yeah. I Kevin Folta: didn't [00:16:00] think about it that way. And, and it's really interesting because I think we're getting to the point and, and I'm just taking a guess that. We'll probably be getting to the point where the economics of this are increasingly more attractive with petroleum costs going high and this sensitivity towards global climate change. We'll talk about that. On the other side of the break, we're speaking with Scott Franklin, who's the co-founder and chief science officer at checker spot. This is collabs talking biotech podcast, and we'll be back in just a moment. And now we're back on, Clara's talking biotech podcast. And we're speaking with Dr. Scott Franklin. Uh, Dr. Franklin is co-founder and CSO of checker spot. And, uh, where is checker spot Scott Franklin: located? So Kevin, our, our headquarters are in Alameda, California, but we also have a manufacturing facilit. For our brand wonder Alpine, which is an outdoor brand in salt lake city, Utah. [00:17:00] Yeah. Kevin Folta: Salt lake city, a really good place for an outdoor. Scott Franklin: absolutely. Kevin Folta: So we talked earlier about the advantages of microalgae. We didn't get much into the engineering of them, that kind of thing, but are they particularly useful or amenable to genetic engineering? And could you say insert a planting that gives them or confer some sort of new metabolic activity or new potential to make a new. Scott Franklin: Oh, absolutely. We do that all the time. Our principle focus is around engineering, uh, fatty acid and triglycerol biosynthesis, but it they're very facile. They're very easy organisms to work with. They're at a molecular genetic level. They're very similar to working with yeast. Um, at least our, our platform organism is not all micro ology work the same way, uh, in terms of how genetic material gets inserted. Our, our platform utilizes homologous for combination. So [00:18:00] just innately naturally, uh, it's a highly recombinant genetic host recom host. So, um, and what that means is we can target, uh, endogenous genes. For disruption for down regulation upregulation but we can also very precisely target where we insert genes to explore particular loci and the impact on gene expression. For example, that's a lot more difficult in a higher plant system or in some other micro systems where genetic insertion events are random. So you really don't control that and you get a lot of position effects in terms of gene expression. Um, So, yeah, it's a very, very, uh, utilitarian Kevin Folta: system. Well, that's really neat. I got a good education today because I never knew that you could do that with algae and, and it's nice. Yeah, because it seems a lot like a direct parallel to what we can do in yeast. Yes. That's Scott Franklin: right. And when we were first developing, when I was at a company called Zyme [00:19:00] and we developed this platform, we were operating in our early days under the assumption that it was gonna be like every other microalgae I knew, and that it was not going to utilize homologous recombination. And it actually took us a while to figure out that, uh, we could do homologous recombination. And once we. Once we figured out that the development really, really took off. Kevin Folta: Well, I'd like to turn the attention to today's hot topic of fuel. And we know that there's been plants that have been genetically engineered to, uh, develop, say high performance jet fuels, things like that. Plants like camelina, but I'm guessing the same approach could be done in micro algae only more efficiently. And is there a price point where you would say a barrel of oil or a gallon of gas would really drive. The production and switch to a microalgae derived fuel, versus those that are coming from say, fossil fuel sources and being pumped out of Scott Franklin: the earth.[00:20:00] You know, I, I don't think you're gonna get to the point where the economics are gonna make a one for one drop in economical. The question is how much of, and there's several questions, but one of those is how much of the transportation fuel, you know, market. Starts to go away because of electrification of transportation generally. I mean, I think in the near term, you're still gonna need rail. You're still gonna need shipping. Um, where I think things like microalgae and plant derived fuels, and I'm, I'm focused mainly on things like biodiesel. Cause I think that's a really good fit. Um, sorry, bio and renewable diesel. I think those are really good fits for triglyceride oils. You're probably looking at a blend strategy. So being able to tailor the triglyceride oil output to fit [00:21:00] really, really well with the specifications you need to make a particular renewable diesel or a jet fuel is I is where I really think you can, you can find applications for these as fuels, but I think in the near term, You know, the next 10 to 15 years, it's going to be as blends to sort of improve the emissions spectra, if you will, of current liquid based fuels Kevin Folta: and fuels are great. But when I look at the website, a checker spot website, I see you're developing a lot of different polymers. Yeah. And can you give us a sense of the kind of interesting polymers you can develop and some of the applications for them? Scott Franklin: Yeah. So the polymer story for checker spot that goes back to our brand. So when Charlie and I started the company and we were thinking about. Platform organism what we would make. We decided to go down a path, um, initially rather than focus on [00:22:00] food or personal care or fuel, uh, we really wanted to focus on materials and we knew it was critical that we be able to animate whatever we were doing in the material space, through a brand. And in order to do that, you have to have a consumer base in that brand. That is going to care very deeply and very passionately about what it is you're making and how you're making it. So, you know, through some exploration in the very early days of the company, we settled on that vertical, that market being outdoor recreation. Because we took a road trip to the outdoor recreation, uh, um, uh, annual convention in salt lake city in 2016. And those people were really, really captivated by what we were proposing to do. And we didn't have any samples. We didn't have any material. [00:23:00] We basically had a concept, but we were kind of getting feedback of if that was something that they thought was worthwhile. Um, and it really validated our conviction that we needed to focus on building a brand in this space. And then developing the materials to service initially that brand and that, that led to the development, the, the Genesis of wonder Alpine. And so we did that in, uh, we brought that to market in 2019 with the general manager, Matt STKs, who had a deep background in back country skiing. So the first materials that we've begun developing are for applications in outdoor and specifically in back country skiing. And what that has led to, and this was our, our, our desire and our hope is a whole suite of applications development for materials that can fit into those end use applications. So a [00:24:00] very demanding, uh, high performance materials that one would use in back country skis. And now in 20. 22, the launch of splitboards and snowboards. So conceptually for us, it wasn't enough and it will never be enough to simply develop a material and then try and get others to adopt it. There's an ethos within the company that we need to animate these technologies through brand. and that brand and the applications serve as a focusing mechanism so that we can begin to understand how do we utilize these materials? How do we make them better? And very importantly, how do we formulate them to deliver the performance properties that we need in an, in an end use application? Kevin Folta: You see, this is what I really love about this is that you're demonstrating that consumers would be interested in maybe paying a premium for something that was coming through this more renewable and sustainable [00:25:00] process and, and this more sustainable platform. And I'm always hesitant to make this podcast sound. Something that could be misunderstood, uh, as an infomercial or something like that. but, but I, and I don't want it to sound like that, but, but at this point, I think it's a great idea. Your technology has an end point of the process. That's something the consumer finds useful, and whether you're using an alternative strategy to get there or biotechnology process to get there, the consumer is excited about the end product and, and that's really cool. It's just another way of showing the biotechnology has great applications to make something the consumer finds good. That's good for an economy. Good for business, ultimately. Good for the. And that's really good because you're doing all of this, uh, manufacturing in a fermentor rather than pulling oil out of the. Scott Franklin: that's right. And, and there's, there's an, um, well, I think for us, there was also an anticipated and now [00:26:00] validated knock on effect of that strategy because it wouldn't be enough just to, you know, take a lot of investors money and build a really cool outdoor brand. Understand me there's huge value in that for checker spot, but the real value has come with that application's development. And not only the connection with the end use consumer of the wonder product, it's the brand adjacencies other brands in the winter sport arena. We call these close adjacencies that look at, wonder Alpine, look at the materials and are now buying those formulated materials. And so the strategy is. That through expanding these concentric circles of what we call adjacencies. We get out into a wider and wider user base of these materials. And as we continue to do applications [00:27:00] development for these wider and wider applications, we create more value within the organization and more value for our materials. That whole process is exactly what the petroleum industry did. It's right out of their playbook. It is identical to how they developed the chemicals industry that grew out of what are we gonna do with the rest of this stuff in a barrel of oil. They had to go and develop all those chemistries and importantly end use applications for those materials. That's exactly what we're doing. And it's a great game plan. Kevin Folta: Yeah. I love it. Put me down for an algae kayak and a bike helmet when you get there. Scott Franklin: exactly. That's right. And the only way, the only way you do that is you have to do that applications development work, because if you're just making the monomer you're, you're seeding. All of that activity to somebody else. And they're on a different timeline. [00:28:00] They're on a different time scale. They have a different agenda and they got a lot of stuff to do. And in our past lives, we found that the ball just doesn't move quickly enough when you're a startup. If you don't take that on board and start to develop applications. Kevin Folta: Yeah. So if I had a kayak that was made from microalgae derived polymers, and I were to use it in the ocean, Would there be a risk of making the microalgae resident in the ocean feel like underachievers Scott Franklin: there's a possibility if they knew where that came from I Kevin Folta: just kind of imagine, you know, look what you guys could have done, you know, I guess it really leads us to the future. Right. You know, how far can this technology go? Um, what can be done in microalgae that's maybe outside of traditional polymer synthesis space. Scott Franklin: Well, I mean, anything that we currently think about making or that we derive from a plant system as a first start, um, [00:29:00] are things we can imagine making in microalgae. So those could be a variety of small molecules. The other thing to appreciate, appreciate about micro alga, the organism itself. Think about it. It's a great delivery. Uh, when we process microalgae coming out of the fermentor, it's a very simple process. We dry it. You can spray dry it or drum dry. It. When you think about what you can package inside that little cell? Um, just like an oil seed. Think of all the possibilities of novel materials, maybe drugs, maybe probiotics, maybe, uh, fertilizers, maybe insecticides biobased insecticides that you're getting aside that you could incorporate in that little package. And now you've got this great delivery vehicle. For a variety of end use applications from, you know, personal care to agriculture, to food. So it's just really, really a great [00:30:00] facile platform for doing a lot. But I will say at checker spot, we are very, very focused right now on a, a suite of outputs from our microalgae and really proving that out and really building a balance sheet around that. And that also takes a lesson from the petroleum industry, um, because. One of the biggest challenge that industrial biotech companies have is you've got to build scale and you've got to build capacity. And that requires a certain degree of focus on the front end of the types of molecules. And it doesn't need to be many, it should be very few that you need to build those processes around so you can achieve scale, um, and economics, because once we can do that, we've kind of got a hardware software model. Our micro little strain is the hardware. We can plug a lot of different pieces of software in there to get to D. Applications and end uses [00:31:00] depending on the software we plug in there. So right now we're really focused on a limited set of triglyceride oils, both internally and with key partners to get to the economics. We need to, to make this eco, to make this a viable industry. Well, when Kevin Folta: you're talking about the economics and you're talking about the software and the hardware, what happens if you peel away and purify. All the other needed molecules, the stuff, the triglycerides you set out to make from all the other stuff. Is there value in what's left over for say animal feed or some other kind of application or is there really a zero waste situation? Scott Franklin: Absolutely cuz again, that's taking another lesson from the petroleum industry. So the petroleum industry has figured out how to utilize every single scrap molecule in a barrel of oil and the, you know, um, you know, the bio industry. Um, needs to do the same thing. So [00:32:00] figuring out what the end use applications are for what we call spent, press cake or bio, you know, uh, dilapidated biomass is definitely something. So it definitely has applications is in animal feed. I think that's probably a relatively low value application. Um, I think there's a lot of applications around whole biomass. Where we deliver a lot of the benefits and properties of the oil, but we use the whole cell. So I think there's a lot of intrinsic value there as well. Kevin Folta: Yeah. Energy bars for skiers. I mean, you can give 'em a helmet and buy them Scott Franklin: lunch. Exactly. That's right. Yeah. Well, Kevin Folta: This is, but this isn't the first company that's tried such things. I think there's been others that have tried to do this kind of work, and you've been at it for a while, but what are some of the biggest criticisms and how have you managed to work around those and achieve the performance levels necessary to make this a really viable [00:33:00] concept? Scott Franklin: Oh, yeah. Well, that's a great question. I mean, that's always the challenge when you're talking to like a dower in DuPont or whomever, and you're a startup and you've gotta, you know, the next biobased material. Um, I think the go to answer. From those companies is bio means lower performance. And I think the key there we alluded to earlier, it's doing the applications development. So again, through the brand in a very demanding consumer space, and I will say not just the consumer space, the, the team at wonder Alpine. So Matt turbans. Pep food. Yes. Um, you know, Alex Andrews, that team are all professional, highly professional, incredibly talented back country, skiers and snowboarders. And when you get your [00:34:00] materials into the hands of those guys, it's not giving it to somebody who's now gonna go and do a couple of runs at the resort. They will part of the language, beat the crap. Out of the product. And so when you can pass muster with those guys, you kind of have their buy in that we've met or exceeded their expectations and to take it one step further. When we've seen these winter sport adjacencies come in, they all have different criteria for the performance of those materials. And to be able to see our materials, meet those specifications. To me, there's no more argument about bio base equals lower performance to me that that argument's gone. It's done. We can absolutely make materials that need exceed the current incumbents. Kevin Folta: Yeah. And that's, what's so exciting to me as someone who thinks about strategic communication and strategic plans as a company, [00:35:00] you've managed to engage a specific market segment who shares the values of sustainability with the company. So you're not just making a product and, and throwing it out there. Uh, you know, with some sort of underlying set of values, you've identified the market that you'll fulfill. Uh, identified the values they ascribe to, and then use a technique that they would really buy into. So they're not just buying the product for the product, they're buying it because of how it was made. And that's really, really a great strategy and it taught me a lot today. So thank you very, very much for joining me today, Scott. I really appreciate it. Scott Franklin: Oh great. It was a PLE it was a pleasure talking to you and, uh, your audience. Kevin Folta: Yeah. And to that audience. Thank you very much for listening to the talking biotech podcast as always, uh, check out collaborative suite of products, that laboratory products that add to the efficiency. It makes the experience a little more fun to have everybody working together in one shared space. So also write reviews over on iTunes or any [00:36:00] place where you consume podcast media. Tele friend. Uh, we continue to grow with more downloads every single week now in our eighth year. Thank you for listening to the talking biotech podcast. And we'll talk to you again next week.