Can Synthetic Biology and Pond Scum Deliver Carbon-Neutral Manufacturing?

Synthetic biology has long promised to make production of medicines, foods, chemicals and materials cheaper and more sustainable. Yet, while many products can now be made through synbio, the bio-based manufacturing revolution is still not here. A major bottleneck to realizing the opportunity of synbio is the production process: the existing options are tricky and expensive, and there still aren’t many of them. An emerging production platform is microalgae, which rely on a cheap and abundant energy source: light.

Provectus Algae is developing technologies to grow microalgae at scale and engineer them to produce diverse biomaterials such as food additives, cosmetics, and fragrances. Prior to founding Provectus Algae, CEO and founder Nusqe Spanton spent nearly 20 years in the aquaculture industry, where he saw first-hand the challenges of growing this microbe. 

In this interview, Spanton explains how synthetic biology is being used in the manufacturing space, what makes algae so interesting (and challenging) as a vehicle for manufacturing, and how to avoid the pitfalls that led to a false start for algal synthetic biology. We start by digging into why Spanton started Provectus.

You’ve founded a couple of companies before Provectus Algae. What did you learn through those experiences?

NUSQE SPANTON: I’ve worked my way up from the bottom to the top in the previous careers that I’ve had. I’ve always had an entrepreneurial mindset. I love to identify problems in markets and try to go at them.

The biggest thing that I’ve learned over the last 20 years is it’s pointless to make something that might have a phenomenal return on investment in a market that doesn’t exist today. If a market doesn’t exist, but here’s this fantastic product that nobody’s ever heard about or seen before, you’re going up against a fundamental challenge in humanity where we like to stay within the boundaries of what we know. It takes a long time and there has to be a clear strategy in order to change people’s mindsets.

Starting Provectus came off the back of having spent over a decade working my guts out trying to get to the top of my craft in aquaculture, producing pearls from oysters.

Ultimately, that’s a luxury good that is highly volatile. It’s not a product that people need at all. They look fantastic, and they make people feel great when they’re wearing them, but it’s not something that we really need in our daily lives to survive. A real turning point for me was in thinking about where I want to be as a human being and how to take all of my learning over the last 20 years and build that into something that is going to generate tangible value for people and change the way we fundamentally do things.

I’ve been growing algae for almost 20 years. I know how hard it is. I saw the biofuel bust. Algae is not, at the moment, suitable to create combustible fuels at scale. But it has the potential to do it if we’re realistic about it. We have to start by identifying a tractable problem where we can apply the value of synthetic biology. We see that value in large scale biomanufacturing. There’s an underlying problem with how we’re manufacturing goods, and it’s that it needs massive inputs, and we’re essentially destroying the planet on how we live today.

Algae gives us opportunities to actually do carbon-negative manufacturing. It’s no different to what we’ve been doing in agriculture for the last thousand years. It’s a plant that takes CO2 and converts that into something that we eat or something that we use. The underlying challenge is that we need to be able to control the product and we need to be able to grow it at scale. And we need to move the needle in a whole range of verticals that aren’t necessarily talked about openly as being serious problems.

We’re starting with a metaphorical ‘empty glass’ that can grow, and there’s nothing or minimal things genetically encoded in it that can be detrimental to your product.

If we look at specialty ingredients such as high-value food and fragrance ingredients, for instance, we’ve got massive problems in the way that we manufacture them today. A huge volume of specialty ingredients are synthetic petrochemical-based. We’re digging it out of the ground, we’re putting it in a flask, and we’re chemically synthesizing these products that we’re putting into our body and into our food chain. Not only is that a problem for emissions into the atmosphere, but it’s a problem for us and our food chains.

Being able to create a biomanufacturing format that does the complete opposite to that is something that has true tangible value. So that’s a real driver for me– not to create one product that has value to customers, but to figure out how to build something where we can have real change by having hundreds if not thousands of facilities at scale, and identify multiple verticals where we can change the paradigm and move us toward carbon negative.

But that’s a fantastical sort of vision, right? How do we do that? We have to deliver value to customers as fast as we possibly can, get to revenue, prove that it can be built out at scale and at a value proposition that works for people. Then we can start to move into areas where this is a really exciting technology.

Why is now the right time to show that synthetic biology can provide value to customers in the manufacturing segment?

What some may not realize is that synthetic biology’s been used for the last 40, 50 years in pharmaceutical applications. It’s only in the last couple of decades that the technology has allowed us to look outside of the really high-value therapeutics verticals and into applications in different markets.

Over the last decade in particular, we’ve seen significant advancements in areas from sequencing, to understanding the functions of genomes, to scaling these technologies and manufacturing the hardware to grow these microbes. Now we can ask: what are the significant applications where we can really change how manufacturing is done and what can really change the world through synbio?

After the biofuel boom and bust in the 2010s, we’re seeing a shift into high-value applications like food and beverage ingredients, cosmetics ingredients, flavorings, and fragrances. Here we can prove the utility of the technology and get it moving really quickly, while building out the infrastructure that’s then required for scaling up.

Can you tell me more about the different types of cells and microbes that are used in synbio? What are the different advantages of them?

We’ve had three predominant modalities, which are all very different from algae: animal cell culture, bacteria, and yeast fermentation. Each different modality has an advantage in different areas based on what the cells are capable of doing and what is commercially viable at scale when you’re moving into scale.

In the therapeutic space, a lot of work uses animal cell culture techniques, because yeast and bacteria can’t always make molecules that work in humans. The downside of using animal cell culture is that it’s exceptionally expensive. The major cost component being keeping the culture sterile. A big proportion of that comes into how you maintain those cells. If humans work in the facilities, they can transfer human-based diseases to the culture, which is a significant risk to the production system and why it’s often been very difficult and expensive. This is why it’s not broadly used across different market verticals apart from the high-value therapeutics-grade products.

In order to look into doing synbio in a microbial format like algae first you’ve got to be able to grow it.

Yeast and bacterial systems are much more flexible in what they’re able to do. However, you’ve got to also pinpoint the target application and hone in on the advantages of each of those microbial sets. Both yeast and bacterial systems grow exceptionally fast and secrete products into the liquid you grow them in, allowing you to harvest the product and purify it very easily and effectively. It’s a simple process where microbes consume sugar and convert it into energy to drive production of the target molecule. The downside of that is that conversion from sugar into energy in this way generally produces a lot of carbon dioxide emissions.

The beauty about these formats is we’ve now got cells where we have a very detailed understanding of how they work and what products they’re capable of creating. We’re starting with a metaphorical ‘empty glass’ that can grow, and there’s nothing or minimal things genetically encoded in it that can be detrimental to your product

But the downside is you’ve got to engineer everything you need in the cell to create the product. That’s an exceptionally difficult thing to do. It takes exceptionally crafted and skilled personnel, and so that’s one of the big bottlenecks in getting these products to market quickly.

What is different about using microalgae as a fourth modality for synbio?

We’ve never really used algae as a modality for synthetic biology before. With algae we have an opportunity to change the way we think about microbes and their capabilities in biomanufacturing. Instead of engineering the entire microbe to get out what you want, we can find the correct microbes or the correct algae species to be able to naturally do the vast majority of what you want. That really changes the focus of how we look at microbes and the feasibility of biomanufacturing in the future. But we’ve got to take a multi-tiered approach, because both looking for the right microbe that can do what you want, and engineering a microbe to make it do what you want, are necessary strategies to get to where we need to go over the next couple of decades.

Microalgae are exceptionally diverse, but they’re an untapped resource that nobody’s really looked into in terms of what it’s capable of doing from a genetic diversity perspective. There could be more than 300,000 species globally, but we really don’t even know how many there are because it hasn’t been looked into in-depth to make large databases. They also have a vast amount of genomic content to explore. Some algae can have a genome that’s 10 times the size of a human being’s. It’s got all of these genes in there that are unexplored that could potentially drive a metabolic process to produce a strawberry flavor, or an animal fat. This really opens up new opportunities.

In order to look into doing synbio in a microbial format like algae, first you’ve got to be able to grow it. This has been the real challenge for the last 50 years. The difficulty there is we’re dealing with a microbe that converts light photon energy into chemical energy. But they’re very, very different to terrestrial plants that grow on the surface of the earth and receive sunlight that is very similar wherever you go in the world.

Algae grow in water–in every aquatic environment on the planet–which means exceptionally different microenvironments. The puddle on the street in front of your house might have 20 algae species growing in there, there’s algae growing in the desert billabongs, in Antarctica, on the surface of the ocean and at 1,000 meters deep, in river systems, in wave action. And the environment is super dynamic. So they’ve evolved to hone in on the type of light that they receive in these environments. If you’ve seen light pass through a prism, it splits all the colors apart and that’s exactly what water does. As you go down through the water column, different light is filtered out. If you’re in a river system that’s brown and murky and churning really rapidly, you might have algae that’s going from the top to the bottom of this river very, very rapidly and it’s getting light and dark cycles very rapidly.

… let’s not brute force biology. We don’t need to engineer everything inside the cell and make the organism do something that it’s not naturally supposed to do.

So we’ve got to be able to deliver light in the way that these algae need it to be delivered. They’ve got particular receptors that can only harness particular light frequencies, and we’ve never even had the technology to deliver light in this way. So that’s first and foremost what we had to do as a company. From there, you can start to understand how the genomes of algae are driven by light and metabolic functions can be switched on or switched off by changing the light.

Then, once we understand how to drive these metabolic processes with the environment that we’re giving to the algae, we can then start to work out how to push this to scale and solve some of the major biomanufacturing pitfalls through the different supply chains.

Then do you see the focus being on tapping into algal diversity as a resource for bioprospecting, or do you envision there being a focus on a couple algae species to develop them as platform for synbio, as we’ve seen for yeast and bacteria?

We’ve got to start with the same concept of using a standard species to run our synthetic biology in algae.

For instance, there are particular species and strains that we use for our peptide platform. We’re still in the early stages of using algae in this format, so, we’ve got to get really good at engineering particular types of products into these chassis, or ‘empty glasses’.

But at the same time, we’ve got to build up huge biomolecular data sets and species libraries to utilize algae across the board. For instance, if we wanted to find a particular specialty ingredient, we would want to be able to search a database and find algae      that could potentially produce it naturally through the right growth and environmental conditions.

We’re going to see a transition over the next couple of years with culturing technology starting to drive bioprospecting and the ability to bring natural products to market that we never thought were possible using any microbial format. You won’t necessarily be using genetic engineering all the time to create those products, but using it where it’s most effective to do so.

How much will the algae synbio field be able to borrow from the tools that people have been developing in other organisms?

The synthetic biology techniques are quite broadly known now and pretty universal across species. We can utilize those in what we’re doing, but we’re thinking about it differently. It’s thinking about it from the perspective of: let’s not brute force biology. We don’t need to engineer everything inside the cell and make the organism do something that it’s not naturally supposed to do. Let’s look at our microbial format and look at what the capabilities are, and then use all of the predetermined knowledge and toolkits to enhance nature instead of brute-forcing something that it’s not supposed to be doing.

That’s an interesting approach. Is that something that you could see then extending out to other types of microbes? Is this a general strategy you think people should be using?

I think there is a shift in the industry. There are a number of synbio and supporting companies that are coming through the pipeline now that have that same approach. I think all approaches are valid. In order to really change the way our manufacturing system works to solve some of the existential threats that we have to humanity right now, you can’t take a pigeonholed approach. Everything is valid and we need to be moving the dial in every single aspect.

But deep tech does take time, and human beings inherently aren’t very smart creatures. We think we’re very smart, but when we start to look into biology we quickly realize that there is a lot that we don’t know. We’ve got to keep pushing the boundaries and keep learning and understanding in order to make synbio into an opportunity to change everything that we do in our daily lives.

The way that the community has gone about commercializing synbio is absolutely necessary to get products into market as quickly as we can. Only once we’ve got products in consumers’ hands and they are higher performance, they have price parity, and they’re solving tangible problems in people’s lives, can we shift the focus to really driving change.

This interview has been edited and condensed.

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  Nusqe Spanton Founder and CEO of Provectus Algae. Nusqe is an algae and aquaculture expert with 17 years experience in international aquaculture production, corporate management and marine biotechnology application

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  Nicole Neuman is an editor at Future, focusing on biology and science. She was previously a senior scientific editor at Cell.