Exclusive: Quercus Biosolutions emerges from stealth to disrupt crop protection with designer mini proteins

Quercus Biosolutions, an ag biotech startup utilizing generative AI to create a brand new class of crop safety merchandise primarily based on designer mini proteins, has emerged from stealth with pre-seed funding from undisclosed traders.

The agency, based final yr by ag trade veterans Dr. Jon Lightner and Matt Crisp, has a strategic partnership with drug discovery startup Ordaos Bio to use the latter’s generative AI platform—initially designed for human medication—to agriculture.

The strategy might probably ship a step change in crop safety, Crisp instructed AgFunderNews.

“We’ve been saying for 20 years that ‘Within the subsequent 5 years, biologicals are going to overhaul chemistry-based options,’ and we’re all one another proper now and saying, ‘Properly, we’ve gotten just a few factors of market share after 20 years and lots of billions of {dollars} of funding.’”

With Quercus’ platform, he claimed, “I really feel like we’re going to attain extra in crop safety utilizing this expertise within the subsequent two years than we now have within the final 20.”

At its core, stated Lightner, “We anticipate this platform can lastly ship the efficacy that growers and farmers affiliate with small molecules [and chemical crop inputs] to the biologicals section.”

Designer proteins

A number of companies in ag biologicals now use mini proteins, also called peptides or micropeptides (small chains of amino acids) relatively than dwelling microorganisms for crop safety functions, citing elevated stability, precision, and consistency.

Nonetheless most gamers sometimes display libraries of naturally occurring proteins to determine these with potential to focus on pests or carry out different crop safety capabilities, stated Lightner, who’s working with Solis Agrosciences for testing, knowledge technology, optimization, and validation.

Quercus, in contrast, is utilizing AI to design mini proteins from scratch, he stated. “We take a look at all attainable proteins, mannequin all attainable buildings, after which check and construct subsets of these in a days-long course of for computational testing. We will then produce them by way of cell-free expression for testing in vitro the subsequent day.”

Ordaos Bio CEO Dave Longo added: “Lots of people declare they’re doing actually de novo protein design, however most AI corporations claiming this are taking an present protein and easily changing the sequence that makes up that protein to get the identical construction.

“As an illustration, when you’ve got one thing that binds to HER2 [Human Epidermal Growth Factor Receptor 2, a common target for breast cancer drugs] they’d take the unique protein and ask the AI, are you able to give us a unique sequence in order that we are able to patent it, with the identical construction as this present protein?

“It’s arduous to name that design. What we’re doing is giving the system all it wants to grasp what your mini protein has to do comparable to crossing the plant cuticle or crossing the cell membrane, after which designing a protein actually from scratch.”

‘Head-to-head comparisons with the perfect chemical options’

Based on Crisp: “I really suppose the identical issues persist for most of the biologicals on the market, whether or not it’s peptides, RNAi, small proteins, massive proteins, or complete microorganisms. I believe an identical set of challenges continues to plague this complete house.”

Creating designer proteins from scratch can clear up many of those issues, claimed Lightner.

“We’re constructing our assays round head-to-head comparisons with the perfect present chemical options. We expect we’ll create an equally massive crop safety class that’s primarily based totally on these novel proteins, with all of the favored regulatory and environmental benefits of biologicals, but additionally a rock strong, constant efficacy of the sort that individuals have achieved with chemistry in agriculture.”

Designing for a number of components without delay

Usually, stated Crisp, companies growing crop safety merchandise take a look at the issue they’re attempting to unravel in a linear trend “ranging from a mode of motion perspective.”

After that, they then deal with all the opposite challenges that come together with growing a industrial product comparable to formulation, stability, provide chain constraints, whether or not it would combine in a tank with different crop safety inputs, and whether or not it may be cost-effectively manufactured by way of precision fermentation on a industrial scale, he stated.

Quercus can design merchandise that consider all of this stuff from the outset, he claimed.

“That’s what will get me so jazzed. We will construct all these necessities proper into our very early screens after which feed these outcomes again into our AI.”

Go the place the cash is: drug discovery

To position Quercus in context, Crisp stated, “I’d say ag is 5-15 years behind the entire technological enabling platform work that’s finished in essentially the most well-funded enviornment of innovation, which is human medication.

“We regarded throughout the AI house in agriculture,” stated Lightner, “however Matt’s view was, if we actually wish to see the slicing fringe of AI, we have to take a look at the pharmaceutical sector.”

Crisp defined: “I left [seed giant] Benson Hill a pair years in the past and since then I’ve been a variety of completely different improvements and alternatives together with newer technology biologicals. However I didn’t see the type of Gen AI that was starting to be deployed within the enviornment of most cancers therapeutics, for instance.

“So my view is, go the place the cash is. Corporations in human medication have been receiving thousands and thousands of {dollars} to develop a number of the most revolutionary platform applied sciences to do bespoke organic design, together with for peptides and proteins. So might we repurpose a kind of platforms for agriculture?

“So Jon and I did some diligence on corporations in human healthcare and had been actually impressed with Ordaos Bio’s platform, and fairly quickly got here to the conclusion that it might speed up a quantum of worth creation in crop safety.”

The enticing factor about a number of the bespoke mini proteins Quercus is growing is that they could possibly be as efficient as artificial chemical compounds, however shall be regulated as biopesticides and won’t persist within the surroundings for many years, claimed Lightner.

“Bt applied sciences [deployed in GM maize and cotton for example] are starting to fail and so we want innovation desperately. And these protein crop protectants can function below the biopesticide framework with the EPA that’s sometimes one million {dollars} to an approval, and fewer than two years. We will create options that we are able to carry to market on a extremely fast timeframe.”

Manufacturing the mini proteins at scale

So can Quercus’s mini proteins be chemically synthesized at scale or would they be expressed in microbial cells by way of precision fermentation?

Based on Lightner: “Most of the proteins we’re working with within the R&D part we’ve had constructed synthetically, however for large-scale manufacturing we might be recombinant protein expression in microbial techniques.”

The proteins would then be extracted, he stated, however this is able to not contain super-costly downstream processing steps. “We consider at scale we are able to compete head-to-head with small molecule chemistry on a price foundation, with enticing margins.”

‘The fashions get higher and higher’

Based on Lightner: “What we’re doing within the subsequent six to 12 months is specializing in recognized websites of motion for explicit crop safety issues. In order that’s a spot the place we’d have a small molecule [chemical] inhibitor right this moment or we’d have a naturally-derived molecule like a Bt protein, and we all know the receptor or the enzyme that these actives inhibit to get the crop protecting impact.”

Quercus is aware of the proteins the receptors work together with and normally already has crystal buildings “as these proteins have been round for many years,” he stated. “We then predict buildings for our [designer] proteins to suit the energetic website or inhibit explicit catalytic residues, for instance.

“We do this computationally first after which check in vitro for these precise interactions. One of many distinctive issues about Ordaos Bio’s strategy is that they’ve constructed a connection between the computational prediction fashions and the in vitro testing, so the check outcomes inform the mannequin, and the fashions get higher and higher.”

He added: “One factor we’ve realized throughout statistical and genomic choice fashions during the last 20 years in ag is that the perfect mannequin is the one we constructed right this moment from all of the out there knowledge… and that mannequin shall be out of date tomorrow.”

Subject degree validation ‘in as little as six months’

Within the subsequent three to 6 months, stated Crisp, Quercus goals to begin conducting “greenhouse and development chamber degree research with the potential to maneuver to subject degree validation in as little as six months, given the velocity of the platform.”

He added: “We see enormous alternative for IP within the house, so we’re trying to set up a powerful IP portfolio based on a novel knowledge set across the software of AI protein design to this crop safety house.”

Defining mini proteins

As for what constitutes a “mini” protein, there’s no agency definition, stated Lightner.

“The necessary factor is we’re proteins with tertiary construction. In different phrases, not only a linear sequence of amino acids that’s wiggling round, however proteins massive sufficient to have structural attributes. I haven’t seen any arduous and quick definitions, however we’re a minimal of 15-20 amino acids and doubtless much more more likely to be 25-50 amino acids.”

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