Biomanufacturing – using an organism to produce a desired molecule, as opposed to chemical synthesis or other production processes – has exploded in previous decades. Today, the products of biomanufacturing can be found everywhere in the food and pharma sectors.
However, most of the cells involved – from the bacteria and yeasts making enzymes and amino acids to the mammalian cells making biopharmaceutical products – are heterotrophic, meaning they get their energy and nutrients from consumption. But beyond the heterotrophs, there is a category of microscopic organisms with a vast and largely untapped array of characteristics. Rather than consuming other life forms, autotrophic microbes like microalgae derive energy from photosynthesis. And Australian startup Provectus Algae thinks that the microalgae category can become the next frontier for biomanufacturing.
“Photosynthetic biomanufacturing is complementary because it is just [so] different and it means that there are abilities that we can make use of that are built into these cell types that are just not necessarily there in some of these other more commonly used biomanufacturing chassis,” explains Provectus Algae’s scientific affairs manager Dr. Chris Fisher.
For example, he says, mastering microalgae as a production system could allow for the bio-manufacture of products that might be toxic for a mammalian cell, or might require complex protein-folding machinery that bacteria don’t have.
“If we want to make use of life's impressive diversity, the skill sets that have been developed over billions of years by [different lifeforms], we have to really broaden our toolkit. Not every problem can be solved by the same small number of approaches.”
Precision photosynthesis
Of course, the cultivation of algae to make products such as pigments is not new. Still, algae is not exactly straightforward to grow, either.
“The idea, at least in principle, is to build bioreactors that are more contained [than open-air raceway ponds], but historically, those technologies haven’t been very good, frankly. Being able to reach the same level of biomass and the same nutrient use was traditionally quite difficult in photobioreactors,” he asserts.
One of Provectus Algae’s specialties is developing technologies to help overcome those bottlenecks and helping customers maximise whatever product they are trying to get out of the algae, using proprietary “precision photosynthesis” technology.
“Everything for algae revolves around light,” explains Dr. Fisher. “It's all about how to capture light, protect themselves from light and make use of light to produce a wide range of metabolites that they need to survive in their niche… what that means is that in certain light conditions, certain genes are turned up, others are turned down.”
In other words, by tightly controlling the amount and types of light the algae are exposed to, Provectus Algae can fine-tune the expression of target genes. “[Imagine] we have an algae species that produces a particularly valuable nutrient. So we can use precision photosynthesis to upregulate its expression in that species.”
Full suite of algae biotech solutions
But Provectus Algae’s offer is far more than just algae production technology and light recipes. Instead, the company is building out end-to-end solutions in algae biotech for application in a variety of industries, with a particular focus on R&D covering everything from molecular discovery, genomics, metabolomics, and synthetic biology approaches to upregulate certain gene expression.
In other words, the company aims to be able to do everything from the basic discovery – “let’s go look and see if there’s valuable materials in these algae species that are not explored” – to the design of industrial systems to exploit it at scale.
“How we typically like to operate with our partners [is that] they approach us with a molecule that they'd like to work with specifically, or a class of bioactives that they're interested in, so we can go through our microalgae library and database and look through the metabolomics and say, ‘do any of the species in our database currently produce that molecule?’…then ultimately pick the species and light recipe that maximises production of that target molecule.”
However, not all of their customers’ queries look like that. Some might not have a specific molecule in mind, but are looking for an alternative to an ingredient or process that they are currently using, something which can offer improvements from a supply chain, cost, or sustainability perspective (since algae-based production is carbon negative, actually consuming CO2 rather than emitting it).
“Often what we're doing is we're partnering with a company that has a challenge. They have an ingredient, a chemical or biologic that they want to produce more of, [or] they want to have access to. And we use algae to explore the molecular space and identify what is the best way to produce this molecule in algae.
“Certainly, just to be abundantly clear, there are cases where algae isn't the answer. As I said, it's a complementary technology to fermentation. But we'll also do that assessment in our initial exploration to say, ‘in the long term, do we think that this is going to be economically feasible? At what scales would we need to produce it? Approximately what would that cost be?’”
High value applications first
Dr. Fisher describes this technology as “industry agnostic”. At the end of the day, Provectus Algae’s focus is building algae into a production platform, and the output from that platform could be used in a variety of different products or applications.
Food ingredients might be the first commercial product from a Provectus Algae production system, as the company is working on pigments to be used in alternative protein products in order to mimic the appearance of blood when the products are raw and adapt its colouration when cooked.
Beyond that, there is at least one application for animal feed already on the drawing board: methane mitigation additives for ruminants. There has been a lot of research into the methane reduction effects seen when certain seaweeds (macro algae) are fed to cattle, and Dr. Fisher says the company is in the very early stages of looking into whether its micro algae can produce the substances behind this effect in a cost-effective manner.
“It is certainly very early stages for us – I would say very much still in the R&D phase,” he cautions. Still, it’s an area which he describes as a “huge opportunity” and where he says there is “a lot of active research happening right now in our R&D team to explore a variety of approaches.” And in the longer term, he says, using algae as an edible delivery system for any number of molecules useful to the animal production sector might be envisaged.
Given that CJ Bio recently made a strategic investment in Provectus Algae, one might wonder whether amino acids would be among the products that Provectus Algae was looking to optimise production for. However, according to Dr. Fisher, the economics for making amino acids in such a specialty system don’t necessarily make sense right now.
“Generally speaking, we prefer to operate in high-value situations, where we’re producing a molecule that is very difficult to typically reach [cost-effective production for, and where] currently the market is demanding exorbitant prices for, and we can come in and make a sensitive alternative for. We are certainly interested in some bulk commodities like amino acids. But I would say in the short term, we’ve largely focused on bioactives versus base nutrients.”
Ultimately, he says, it’s still a little early in this relationship to define what the partnership between Provectus Algae and CJ Bio will look like. “I think we both see a tremendous amount of value in working with each other. From our perspective, CJ Bio has been in [the biomanufacturing] space a long time, and for some of those specific nutrients that we’re talking about, they’re a world leader – their biomanufacturing technologies are the standard, the benchmark that everyone’s operating against…
“But as we said, our approach using photosynthetic microalgae is unique and it's quite different from what they've done. So there may be opportunities for us to collaborate.”