🎥Insulin… from black soldier flies? FlyBlast makes the case for bugs vs microbes for recombinant protein production

Right now, recombinant proteins are typically produced by microbes in big steel bioreactors. But insects could make smarter and more cost-effective hosts, claims Antwerp, Belgium-based startup FlyBlast, which genetically engineers black soldier flies to produce insulin and other high-value proteins.

But is its initial strategy of targeting the nascent—and cash-strapped—cultivated meat industry a risky one?

AgFunderNews (AFN) caught up with founder and CEO Johan Jacobs (JJ) at the Future Food-Tech summit in London to find out more…

AFN: Why are insects potentially a better host than microbes for producing these high-value animal proteins?

JJ: At FlyBlast, we’ve genetically modified the black soldier fly to produce human insulin and other recombinant proteins and growth factors specifically for cultivated meat [which uses these costly proteins in cell culture media].

Molecules such as insulin, transferrin, IGF1, FGF2, and EGF represent up to 85% of the cost of growth medium [for cultivated meat]. By mass-producing these biomolecules in insect-bioconversion facilities, we can cut their cost by 95%, and blast through this bottleneck.

The biggest advantage [of black soldier flies over genetically engineered microbes as production vehicles for such proteins] is that you can farm the black soldier fly at a very large scale and very cheaply, because the whole industry has been scaled to bio-convert side streams into insect protein and lipids. We’re just adding a level of technology and profitability, because these molecules are very high value.

The capex costs [of expressing insulin in black soldier flies] are completely different [to the costs of precision fermentation using microbes], and also the capex cost is taken care of by the regular insect products. This is just another revenue stream on top of that. But also what you need to consider is that the molecules we’re targeting are specifically animal proteins. It’s a lot easier to produce animal molecules in animals than in yeast or in bacteria.

We started out in our feasibility study looking at whether insects, for example, have insulin-like pathways? And they do. They have molecules that look very much like human or chicken insulin, so asking them to produce humans insulin, for an insect, it’s a lot easier than for bacteria or even plants, which do not [naturally] have that pathway.

AFN: Isn’t building a business to meet the needs of the cultivated meat industry a bit risky?

JJ: Cultivated meat is our focus, and it is a market that still needs to happen, and so that contains a risk. But two of my cofounders come from that market [several FlyBlast team members previously worked at Antwerp-based cultivated fat startup Peace of Meat, which was liquidated by owner Steakholder Foods last year] and we believe that we have one of the keys to make it happen.

Cultivated meat is going to happen. It will. The question is when, and that’s for our investors a very important question because they need a return within an acceptable time frame. So we are looking at other markets. We chose insulin as the first product because it’s obvious what the alternative markets are. It’s human insulin, cheaply and at scale, so the whole diabetics market is out there.

But basically our technology platform is a great platform…  we can produce most animal-derived molecules, proteins, but even enzymes on our tech platform.

We offer genetic enhancement services in two forms, so we introduce entirely new genes to the black soldier fly DNA, enabling the expression of molecules not naturally present in the species, such as human insulin. But we can also overexpress or suppress an existing gene in the wild-type DNA to modify traits such as protein content, amino acid profile, or fatty acid composition [through licensing agreements with insect farmers/processors].

AFN: If you can make human insulin, why not go after the human health market?

JJ: It’s a very good question, but two of my cofounders come from cultivated meat and they had identified that [sourcing more affordable cell culture media ingredients such as insulin] as the biggest problem for that industry, which is also an industry where you can have a massive impact in terms of climate.

Of course, we have an eye on the human pharmaceutical market, the diabetics market, but we’re really going to need a bigger boat to take that on, because just in terms of [securing] regulatory [approvals] you’re going to need $10 million just to get the paperwork done and then you need to have validated that you have the right molecule at the right purity, etc. We’re going to take a couple of steps, and when we get to a certain point where we have those validation points, then we can raise the funds for the biopharmaceutical market.

AFN: Why use black soldier flies versus fruit flies or other insects as your host organism?

JJ: It’s all about upscaling. I’ve had an insect farming company for 10 years [Millibeter, which was sold to [the now-defunct] AgriProtein in 2019]. So we looked at a lot of different insects, and it’s about how you scale something in a reliable and in a cheap way, and a lot of the companies ended up with black soldier flies or mealworms. Yes, you can, of course, farm fruit flies, but to do a lot of them cheaply and reliably, it’s very hard, whereas there are factories out there that produce 10 tons of insect biomass per day.

AFN: After the insulin is extracted, can the material left over continue into the insect supply chain?

JJ: So the other insect products, insect protein, insect lipids, etc, could technically be used in a regular insect value chain, except that in some geographies because it is GMO, it will not be accepted as livestock feed, for example.

But there are a lot of technical applications which are outside of the food chain. And there they can use proteins and lipids. For example, if you make technical lubricants on an industrial scale, it doesn’t matter whether the lipids are from a GMO source or not.

And on the frass [insect waste], we need to take care taking it out to the field as it does contain GMO traces, so we’re going to pyrolyze it into biochar.

AFN: What kind of progress have you made so far?

JJ: Within a year… we have a stable breeding line that expresses human insulin at very high yields. Now we need to take the molecule out and supply the samples to our customers, and then work with our customers on which molecules they want next.

Further reading:

From novelty to necessity? The evolution of insect farming

🎥Cultivated meat: ‘There’s a valley of death we’re not going to cross without a massive infusion of public investment’

Crunch time for cultivated meat: ‘Probably 70-90% of players will fail in the next year’