Move over stevia? Joywell Foods raises $6.9m, aims to commercialize sweet proteins in 18-24 months

By Elaine Watson

- Last updated on GMT

Miraculin is a glycoprotein with the ability to make sour substances taste sweet (Picture: Gettyimages/passion4nature)
Miraculin is a glycoprotein with the ability to make sour substances taste sweet (Picture: Gettyimages/passion4nature)

Related tags Stevia miracle fruit miraculin brazzein Sweeteners curculin

Foods and beverages sweetened with miraculin, brazzein and curculin - proteins found in exotic fruits that can be produced far more efficiently via microbial fermentation - could hit the US market in less than two years, offering formulators intriguing alternatives to stevia and monk fruit to expand the sugar reduction toolkit.

While stevia and monk fruit sweeteners have improved significantly in recent years as firms have homed in on the more sugar-like (but also more scarce) steviol glycosides such as Reb M, “they still don’t taste exactly like sugar​” and formulators are always looking for other natural options, claims Dr Jason Ryder, CTO at California-based startup Joywell Foods (formerly 'Miraculex').

Proteins such as miraculin (from the ‘miracle berry’ or Synsepalum dulcificum​), brazzein (from the fruit of Pentadiplandra brazzeana Baillon​) and curculin (from the fruit of Curculigo latifolia​) can deliver a more sugar-like sweetness profile, but have not been commercialized as it’s not economically viable to produce meaningful quantities by extracting them from fruit, he told FoodNavigator-USA.

However, Joywell​ - one of a new breed of startups using synthetic biology to  ‘program’ microbes to express proteins and other components found in plants by using DNA sequences from the plants in question – is on a mission to bring these exotic proteins to the mainstream of food formulation.

$6.9m funding round

The Davis, Calif-based startup – which has just raised $6.9m in a Series A round led by Kraft Heinz-backed venture fund Evolv Ventures and supported by Khosla Ventures, SOSV, Alumni Ventures Group and others – “takes the DNA from the plant and drops it into a microbe ​[yeast] to express the protein via a fermentation process,” ​explained Dr Ryder.

And these proteins could feature in yogurts, beverages, and a wide range of other products, according to Ryder, who has just co-authored a peer-reviewed toxicology study​ on miraculin along with an R&D executive from Coca-Cola, which will help inform GRAS dossiers the company is preparing both for plant-derived and fermentation-derived versions.

“We’ve developed a great relationship with the FDA and we’re in the process of finishing our dossier on plant-based miraculin and we'll then put together a dossier covering the fermentation process​,” ​said Dr Ryder.

While fermentation is the gamechanger for industrial-scale applications, there is a supply of berries from which miraculin can be extracted both for sampling purposes, but also for smaller-scale product launches, or for companies that don't want to use a fermentation-derived product, he said.

"Miracle berries are grown natively in West Africa and southern Taiwan and there's even a domestic source in southern Florida, so there are quantities of the fruit available. There will be consumers that want plant-based and we will be able to offer that, but if you could also do this via fermentation at a much larger scale for lower cost, why wouldn't you?"

‘We’re talking with a lot of CPG companies’

Joywell – which has “a lot of trade secrets​” but has also filed three provisional patent applications covering its innovations - will use the new capital to build-out its proprietary technology platform, broaden its sweet protein portfolio, expand R&D operations and test a number of consumer offerings through direct to consumer and limited retail to show the market what the ingredients can do, said Dr Ryder.

However, Joywell is at its core, an ingredient company that will partner and co-develop with CPG companies, he said.

“We view these three proteins as tools and we’re talking with a lot of CPG companies and flavor houses about how they could be used in formulations. Many CPG companies have experimented with these sweet proteins in the past but their frustration is that they haven’t been able to procure them at any meaningful scale to commercialize, and they are excited that we can do that.”

Miracle-fruit-GettyImages-passion4nature cropped

"The fruit of Synepalum dulcificum, also known as Richadella dulcifica, a shrub native to tropical West Africa, has been known for over a century to make sour substances taste sweet. The West African natives chewed the 'miraculous berry,' also referred to as 'sweet berry,' prior to food consumption to make acidic foods with an overly sour taste, such as kankies (sour cornbread), or intensely sour drinks, such as palm wine and pitto (a beer made from fermented grain), more palatable. The unusual ability of these red berries to modify a sour into sweet taste earned them the name ‘Miracle Fruit.'"

SourceSafety assessment of miraculin using in silico and in vitro digestibility analyses​, ​Food & Chemical Toxicology, 2019

Miraculin, brazzein, curculin

Miraculin, for example, is not sweet in and of itself, but when paired with an acid, it delivers intense sweetness that can be dialed up or down in an application, enabling companies to make significant reductions in sugar in products such as yogurt, juice beverages, or diet cola, he said.

“The American consumer doesn’t always like the tartness or sourness of a Greek yogurt, for example, so many brands add a lot of sugar. If you formulate with miraculin, you don’t have to do that. It’s the same with granola, and with lemonade, or other sugary acidic drinks with ascorbic acid or citric acid added.

“Any applications where sugar is not a functional ingredient – and is only added for sweetness - are prime targets for our sweet proteins. Cola and juices are also acidic products andI don’t think it’s an accident that Coca-Cola is part of our safety study, as they are interested in it for lots of applications.”

Brazzein is a high potency natural sweetener, and might be a better choice than miraculin in applications where you don’t want to formulate with acid, he said. “Coffee is one application I’d point to, but we’re talking to companies about a range of applications.”

Curculin, meanwhile, has unique functionality, exhibiting sweet-tasting and taste-modifying properties, he said.  

Heat sensitivity

Asked about heat sensitivity, he said. “When the proteins are dry, you can heat them up well beyond sterilization temperatures, but when they are in their wet form, you have to be more careful.

“Like all functional proteins, if you heat them up beyond a certain temperature, they will unfold and become unfunctional; but some of them have higher heat resistance than others, so we are testing their limits to make sure that we identify the right applications for each one of these proteins.”

Labeling and regulation

As miraculin produced via fermentation does not contain any genetically engineered yeast, it is not subject to bioengineered food labeling, but it would likely not meet the criteria for Non GMO Project certification​ (version 15) as it is derived from a genetically engineered microorganism (p33) and is also a 'derivative' of synthetic biology (pp7-8).

However, the fermentation-based miraculin protein is identical to the miraculin extracted directly from berries, said Dr Ryder.

While consumer enthusiasm for miraculin produced via fermentation may to some degree depend on how it is labeled on the ingredients list (this is still to be determined), a growing number of high-profile startups from Perfect Day to Impossible Foods have proved that consumers will accept ingredients made from engineered microbes, if there is a consumer benefit, he claimed.

And finding a natural protein that can enable firms to slash sugar in everything from beverages to yogurts without imparting a bitter aftertaste is a strong motivator, he added, noting that stevia and monk fruit are still no match for sugar, even if products have improved significantly in recent years.

Miraculin and safety

According to a study recently published in Food & Chemical Toxicology, penned by researchers at Coca-Cola, Intertek, and Miraculex (now Joywell Foods), and funded by Coca-Cola and Miraculex:"The safety of miraculin has been evaluated using an approach proposed by the FAO of the UN and the WHO for assessing the safety of novel proteins.

"Miraculin was shown to be fully and rapidly digested by pepsin in an in vitro digestibility assay. The proteomic analysis of miraculin's pepsin digests further corroborated that it is highly unlikely that any of the protein will remain intact within the gastrointestinal tract for potential absorption. The potential allergenicity and toxigenicity of miraculin, investigated using in silico bioinformatic analyses, demonstrated that miraculin does not represent a risk of allergy or toxicity to humans with low potential for cross-reactivity with other allergens.

"The results of a sensory study, characterizing the taste receptor activity of miraculin, showed that the taste-modifying effect of miraculin at the concentration intended for product development has a rapid onset and disappearance with no desensitizing impact on the receptor.

"Overall, the results of this study demonstrate that the use of miraculin to impact the sensory qualities of orally administered products with a bitter/sour taste profile is not associated with any safety concerns."

SourceSafety assessment of miraculin using in silico and in vitro digestibility analyses​, Food & Chemical Toxicology,  2019

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