Soon in your beverage: Israeli protein-based sugar substitute

Israeli food-tech company Amai, based in Rehovot, has been developing a healthy sugar substitute for years. The sweetener, a computer-designed protein, made a significant step forward this week with several new regulatory approvals for its use in the food industry.

Amai (which means "sweet" in Japanese) announced that its calorie-free protein sweetener, Sweelin (a registered trademark), has received multiple regulatory approvals, including GRAS status (Generally Recognized as Safe) in the U.S., and an approval from the Flavor and Extract Manufacturers Association (FEMA). The final and most stringent hurdle, GRAS approval from the U.S. Food and Drug Administration (FDA), is still pending.

Amai embarked on this mission several years ago to create a new sugar alternative. Many existing sugar substitutes used in diet drinks, candy, and other food products are known to have significant drawbacks. Some break down when exposed to heat, rendering them unsuitable for baking, while others can cause digestive discomfort when consumed in large quantities. There is a product called thaumatin that meets many requirements, but it’s prohibitively expensive, rare, and has a short shelf life. Moreover, it's more of a flavor enhancer than a full sugar replacement.

Amai's innovation stands out because it’s a protein that can be digested naturally. The protein is engineered by altering the sequences of amino acids, the building blocks of proteins. It can be produced at scale and at relatively low cost by fermentation in yeast. For comparison, one kilogram of Sweelin is equivalent to three tons of sugar, making it a cost-effective option for the industry.

The protein interacts with taste receptors on the tongue to signal sweetness to the brain—without calories or the health risks associated with excessive sugar consumption, one of the major issues in the Western world.

The idea of a protein-based sugar substitute has been brewing for years in the mind of Dr. Ilan Samish, Amai’s founder, who specializes in computational protein design. This emerging field involves designing proteins that don’t naturally occur in nature, using powerful computers and cloud computing infrastructure, like AWS. Recently, Professor David Baker won a Nobel Prize for advancements in this field.

“Software Versions” of Proteins

In an interview with Walla, Dr. Naama Kopelman, head of computational protein design and intellectual property at Amai, explained the process: "Protein design is about modifying proteins to meet a specific purpose with desired characteristics. In computational protein design, we use a variety of tools, such as machine learning and molecular dynamics simulations, to better understand our protein and pinpoint which amino acids we should focus on changing to enhance the desired traits."

However, Kopelman noted that human expertise still plays a critical role in the development process. Scientists rely on their knowledge of similar proteins and the characteristics of the designed protein, as well as proteins with the traits they are seeking. "For example, we draw inspiration from proteins in organisms that live in extreme environments to adapt them for heat resistance in baking."

Amai began with monellin, a naturally sweet protein found in the Serendipity berry in Africa. Although extremely sweet, it wasn’t stable enough for the food industry. Academics engineered a version of the protein by linking its two subunits to form a single, more stable unit. This became Amai’s starting point. "Structurally, it's identical to the protein in the African fruit, but a bit more stable. Early on, Samish saw its potential for improvement and adaptation to the food industry. Our primary goal was to increase its stability, while also enhancing its sweetness," Kopelman explained.

"The current product, named Sweelin, is also known by the code DM31 (short for Designer Monellin), an improved version of an earlier model, DM9. We enhanced the stability and re-engineered a specific vulnerable site in the molecule by shortening a loop, resulting in a more compact and stable structure. This change improved heat resistance, which is crucial for the food industry. Heat resistance also acts as a simulation for product shelf life under suboptimal conditions," Kopelman added.

The approvals announced by Amai this week bring Sweelin closer to being available on store shelves. As early as next year, consumers may see products labeled "sweetened by Sweelin," much like the "Intel inside" label on computers—another source of Israeli pride.