Synthetic biology has long held out the prospect of making medicines, foods, chemicals, and materials less costly and more sustainable to produce. Yet although many products can now be manufactured with synbio, the bio-based manufacturing revolution has not arrived. A key obstacle to unlocking synbio’s potential is the production process: current choices are difficult and costly, and there still are not many of them. One developing production platform is microalgae, which depend on a cheap and plentiful energy source: light.
Provectus Algae is building technologies to cultivate microalgae at scale and engineer them to make varied biomaterials such as food additives, cosmetics, and fragrances. Before starting Provectus Algae, CEO and founder Nusqe Spanton spent almost 20 years in aquaculture, where he experienced firsthand the difficulties of growing this microbe.
In this interview, Spanton lays out how synthetic biology is being applied in manufacturing, what makes algae such an intriguing and difficult manufacturing platform, and how to sidestep the mistakes that caused algal synthetic biology to stumble at first. We begin by exploring why Spanton launched Provectus.
You’ve founded a couple of companies before Provectus Algae. What did you learn through those experiences?
NUSQE SPANTON: In my earlier careers, I worked my way from the very bottom to the top. I’ve always had an entrepreneurial way of thinking. I enjoy spotting problems in markets and then trying to tackle them.
The main lesson I’ve taken from the past 20 years is that it makes no sense to build something that could have an extraordinary return on investment in a market that does not exist yet. If there is no market, but you have a remarkable product that nobody has ever heard of or seen before, you are facing a basic human challenge: we prefer to stay inside what we already know. Changing that mindset takes a long time and needs a clear strategy.
Starting Provectus followed more than a decade of me working tirelessly to reach the peak of my craft in aquaculture, producing pearls from oysters.
In the end, that is a luxury item and a very unstable one. It is not something people need at all. They look beautiful, and they make people feel wonderful when they wear them, but it is not really something we need in everyday life to stay alive. A major turning point for me was thinking about where I want to be as a person and how to use everything I have learned over the last 20 years to build something that will create real value for people and alter the way we fundamentally do things.
I have been growing algae for nearly 20 years. I know how difficult it is. I watched the biofuel collapse. At the moment, algae is not suitable for making combustible fuels at scale. But it has the potential to do so if we stay realistic. We have to begin by finding a manageable problem where we can use the value of synthetic biology. We see that value in large-scale biomanufacturing. There is a basic problem with how we make goods, and it is that it demands enormous inputs, and we are essentially ruining the planet through the way we live today.
Algae gives us a chance to actually do carbon-negative manufacturing. It is no different from what we have been doing in agriculture for the past thousand years. It is a plant that takes CO2 and turns it into something we eat or something we use. The basic 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 shift the needle across a whole range of verticals that are not necessarily discussed openly as serious problems.
We are starting with a metaphorical ‘empty glass’ that can grow, and there is nothing or only minimal things genetically encoded in it that can be harmful to your product.
If we consider specialty ingredients such as high-value food and fragrance ingredients, for example, we face huge problems in how we manufacture them today. A large volume of specialty ingredients are synthetic and petrochemical-based. We are pulling it from the ground, placing it in a flask, and chemically synthesizing these products that we put into our bodies and into our food chain. That is not only a problem because of emissions into the atmosphere, but also a problem for us and our food chains.
The ability to create a biomanufacturing format that does the exact opposite is something with genuine tangible value. So that is a real motivation for me—not to make one product that has value for customers, but to work out how to build something where we can create 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 is a kind of fantastical vision, right? How do we do that? We have to deliver value to customers as quickly as we possibly can, reach revenue, prove that it can be built out at scale and at a value proposition that works for people. Then we can begin 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 people may not know is that synthetic biology has been used for the last 40, 50 years in pharmaceutical applications. It is only in the last couple of decades that the technology has enabled us to look beyond the very high-value therapeutics verticals and toward applications in other markets.
Over the past decade especially, we have seen major advances in areas ranging from sequencing, to understanding genome functions, to scaling these technologies and manufacturing the hardware used to grow these microbes. Now we can ask: what are the major applications where we can truly change how manufacturing is done and what can really change the world through synbio?
Following the biofuel boom and bust in the 2010s, we are seeing a move toward high-value applications such as food and beverage ingredients, cosmetics ingredients, flavorings, and fragrances. Here we can demonstrate the usefulness of the technology and get it moving very quickly, while building out the infrastructure that is then needed 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 have had three dominant modalities, which are all very different from algae: animal cell culture, bacteria, and yeast fermentation. Each separate modality has an advantage in different areas depending on what the cells can do and what is commercially viable at scale when you are moving into scale.
In the therapeutic space, a lot of work uses animal cell culture techniques, because yeast and bacteria cannot always make molecules that work in humans. The downside of using animal cell culture is that it is exceptionally expensive. The major cost component is keeping the culture sterile. A large part of that comes from 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 has often been very difficult and expensive. This is why it is not widely used across different market verticals apart from high-value therapeutics-grade products.
In order to look into doing synbio in a microbial format like algae first you have got to be able to grow it.
Yeast and bacterial systems are much more flexible in what they can do. However, you also have to identify the target application and focus on the strengths of each of those microbial sets. Both yeast and bacterial systems grow exceptionally fast and secrete products into the liquid they are grown in, allowing you to harvest the product and purify it very easily and effectively. It is a simple process in which microbes consume sugar and convert it into energy to drive production of the target molecule. The downside is that conversion from sugar into energy in this way generally creates a lot of carbon dioxide emissions.
The beauty of these formats is that we now have cells where we have a very detailed understanding of how they work and what products they are capable of creating. We are starting with a metaphorical ‘empty glass’ that can grow, and there is nothing or only minimal things genetically encoded in it that can be harmful to your product
But the drawback is that you have to build into the cell everything required to make the product. That is an extraordinarily hard thing to accomplish. It requires extremely well-designed and highly skilled people, and that is one of the major bottlenecks to bringing these products to market rapidly.
What is different about using microalgae as a fourth modality for synbio?
We have really never used algae as a modality for synthetic biology before. With algae, we have a chance to rethink how we view microbes and what they can do in biomanufacturing. Rather than engineering the whole microbe to produce what we want, we can identify the right microbes or the right algae species that can naturally do most of what we need. That truly shifts the way we think about microbes and the future feasibility of biomanufacturing. But we need to take a multi-tiered approach, because both searching for the right microbe that can do what you want and engineering a microbe to make it do what you want are essential strategies for getting to where we need to be over the next couple of decades.
Microalgae are incredibly varied, yet they are an untapped resource that nobody has really examined in terms of what it can do from a genetic diversity standpoint. There may be more than 300,000 species worldwide, but we do not even really know how many exist because it has not been studied in depth enough to build large databases. They also contain a huge amount of genomic material to investigate. Some algae can have a genome 10 times the size of a human being’s. It contains all of these unexplored genes that could potentially drive a metabolic pathway to make a strawberry flavor or an animal fat. This really creates new opportunities.
To explore synbio in a microbial form like algae, first you have to be able to grow it. That has been the true challenge for the past 50 years. The difficulty is that we are working with a microbe that turns light photon energy into chemical energy. But they are very, very different from land plants that grow on the earth’s surface and receive sunlight that is highly similar wherever you are in the world.
Algae grow in water—in every aquatic environment on the planet—which means extremely different microenvironments. The puddle on the street outside your home might have 20 algae species growing in it, there is algae growing in desert billabongs, in Antarctica, on the ocean surface and 1,000 meters down, in river systems, in wave action. And the environment is highly dynamic. So they have evolved to tune themselves to the kind of light they receive in these settings. If you have seen light go through a prism, it separates all the colors, and that is exactly what water does. As you move down through the water column, different light is filtered away. If you are in a river system that is brown and murky and churning very quickly, you might have algae moving from the top to the bottom of that river very, very rapidly, and it is experiencing light and dark cycles very rapidly.
… let’s not brute force biology. We do not need to engineer everything inside the cell and make the organism do something it is not naturally meant to do.
So we have to be able to deliver light in the way these algae need it delivered. They have specific receptors that can only capture particular light frequencies, and we have never even had the technology to deliver light this way. So that was first and foremost what we had to do as a company. From there, you can begin to understand how algae genomes are shaped by light and how metabolic functions can be turned on or turned off by changing the light.
Then, once we understand how to drive these metabolic processes with the environment we provide to the algae, we can start figuring out how to take this to scale and address some of the major biomanufacturing pitfalls through the various 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 have seen for yeast and bacteria?
We have to begin with the same idea of using a standard species to run our synthetic biology in algae.
For example, there are certain species and strains that we use for our peptide platform. We are still in the early phases of using algae in this format, so we have to get very good at engineering particular kinds of products into these chassis, or ‘empty glasses’.
At the same time, we have to build massive biomolecular data sets and species libraries to use algae across the board. For example, 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 make it naturally through the right growth and environmental conditions.
We are going to see a shift over the next couple of years, with culturing technology beginning to drive bioprospecting and the ability to bring natural products to market that we never thought were possible in any microbial format. You will not necessarily be using genetic engineering all the time to create those products, but using it where it is 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?
Synthetic biology techniques are now fairly widely understood and pretty much universal across species. We can make use of those in what we are doing, but we are approaching it differently. It is about looking at it from the perspective of: let’s not brute force biology. We do not need to engineer everything inside the cell and make the organism do something it is not naturally meant to do. Let’s look at our microbial format and see what the capabilities are, and then use all of the preexisting knowledge and toolkits to enhance nature instead of brute-forcing something it is not meant to be doing.
That is 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. To truly change the way our manufacturing system operates to solve some of the existential threats that we face as humanity right now, you cannot 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 are inherently not very smart creatures. We think we are very smart, but when we start looking into biology we quickly realize that there is a lot we do not know. We have to keep pushing the boundaries and keep learning and understanding in order to make synbio an opportunity to change everything we do in our daily lives.
The way the community has approached commercializing synbio is absolutely necessary to get products into market as quickly as we can. Only once we have products in consumers’ hands and they are higher performance, have price parity, and are solving tangible problems in people’s lives, can we shift the focus to truly driving change.
This interview has been edited and condensed.