Protein discovery startup Shiru has teamed up with Ajinomoto Health & Nutrition Partners, part of ingredients giant Ajinomoto, to develop and commercialize sweet proteins: high intensity natural sweeteners that can replace sugar in beverages and other products.
Natural sweeteners such as stevia and monk fruit have improved significantly in recent years. However, sweet proteins—which are found in fruits and berries that grow near the equator and can be up to 5,000x sweeter than sugar with no impact on blood glucose—add an exciting new dimension to the natural sugar-reduction toolbox, Shiru founder and CEO Dr. Jasmin Hume told AgFunderNews.
The challenge, she says, has been two-fold. First, identifying proteins in nature with the right kind of sweetness (without linger, stability issues, etc). And second, coming up with cost effective production platforms to produce them at scale (typically via microbial fermentation, although some firms are looking at expressing them in corn).
Shiru, which recently launched Flourish, a first-of-its-kind discovery platform and marketplace for proteins, is working with Ajinomoto Health & Nutrition Partners to identify sweet proteins that meet both criteria, said Hume.
“There are about a dozen known sweet proteins out there. And not all of them are perfect. Some of them have issues such as delayed onset or lingering or stability, so not maintaining the same structure or the same potency after processing such as shear or pressure or temperature.
“Shiru’s hypothesis has been that there are likely much more than a dozen sweet proteins out there, but it’s very difficult to find them if you don’t have the right tools. And so this is a great testbed for our Flourish technology to be able to say we have the biggest database of natural proteins in the world and we have the tools to be able to mine that database.
“We’re looking for proteins that are both sweet and potentially more stable and easier to formulate with than the ones that we already know about [such as brazzein].”
Cost effective production systems
As for the second part of the equation, achieving cost-effective production of the sweet protein via precision fermentation, Shiru’s platform can also identify “how likely the protein is to be able to be expressed in a way that makes it manufacturable,” said Hume.
“So it’s a case of what is it about the proteins that make them likely to be expressed in common hosts for scaled production such as yeast, E. coli, fungal hosts, and so on. Are they secreted [by the microbe into the fermentation broth] so the DSP [downstream processing] is going to be much more suitable, for example?
“So we’re throwing all of our tools at this problem, to be able to identify sweet proteins that are not only high performance but can also be scaled up. And then Ajinomoto is obviously world class when it comes to fermentation and ingredient formulation. So this partnership is really leveraging the strengths of both parties.”
While you can’t patent a protein sequence found in nature, Shiru can patent the application of that sequence “in a new way that was not obvious,” said Hume.
“So in this case, it would be finding natural proteins that nobody knew to be sweet before, and as per this partnership, we would be able to negotiate an agreement with Ajinomoto Health & Nutrition Partners whereby they are essentially licensing that technology [from Shiru], most likely that would be exclusive within certain fields of use, so well-defined categories within food and beverage.”
Importantly for the startup, which engaged in a round of layoffs at the tail end of 2023 in order to conserve cash, partnerships such as this can immediately generate revenue, said Hume.
“Hopefully there will be downstream value share; that’s what we expect in terms of the licensing and royalties that would result when we’re scaling ingredients. But for right now, it’s been a critical pursuit to monetize our technology as it is. And we have a digital platform that enables us to do that fairly quickly.”
She added: “This is the first partnership that we’re announcing but we have other ones that are in the works with global corporations.”
Protein discovery platform
Via a simple web interface, Shiru’s recently-launched ProteinDiscovery.ai tool lets users search a database of 33 million+ molecules by protein sequence, functional use, and successful expression (how efficiently the protein might be expressed in microbes via precision fermentation).
According to Hume, customers don’t need to come to Shiru with a known protein. “They can come to us with a problem statement, such as, ‘We need a natural emulsifier that’s stable under acidic conditions,’ or ‘We’re looking for plant proteins that mimic animal proteins such as casein,’ and Shiru can identify solutions. We then query our database using our proprietary and trained machine learning methods to predict which natural proteins are going to have the desired performance parameters.”
One particularly attractive aspect of the platform is the ‘Expressor’ tool, she said, noting that it’s not much use to find a fantastically functional protein found in minuscule quantities in an exotic plant if it’s not viable to produce it cost-effectively in a microbial expression system either because the yields are so low.
According to Hume: “We have trained models to be able to predict protein expression in microbial systems. That is so important because in many cases, folks know of a very specific protein that they want to make and a lot of times that protein is not really suitable for expression in microbes, so they have to kind of brute force it.
“But what we’re providing is a catalogue of other proteins that have the same functionality, but maybe express a whole lot better in a microbial fermentation process.”
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