Molecular farming: BioBetter utilizes tobacco plants as animal-free bioreactors for cell-based meat

12 Sep 2023 --- Food-tech start-up BioBetter has opened its first food-grade pilot facility to accelerate the production of key growth factors for the cultivated meat industry. The Israel-based company has pioneered a unique protein manufacturing platform for producing growth factors (GFs) using tobacco plants as self-sustained, animal-free bioreactors.

Speaking to Food Ingredients First, Amit Yaari, CEO of BioBetter, says: “Our technology is based on common industrial equipment, which is found in many agricultural processing plants, and requires no custom or pharma-based concepts and equipment that are bottlenecking and expensive.”

“The agricultural scale-up is straightforward and requires no capital expenditures (CaPex) investment. To accelerate our scale-up, we are teaming up with established agriculture manufacturers that already have a suitable manufacturing facility, equipment, ISO 22000 and production expertise that can expedite our entry into the market.”

According to a Good Food Institute report from January 2023, the cultivated meat market is expected to reach between 400,000 to 2.1 million metric tons in 2030, which is between 0.1% and 0.56% of the total meat market, respectively, observes Yaari.

The company engineers the plants to be sterile to avoid the escape of recombinant DNA into the ecosystem. (Credit: Photographer, Rotem Golan)He also remarks that it is very significant that we found a new, sustainable proposal for tobacco leaves. 

“This new market needs to match exactly our technological advantages in every aspect – the scalability, the low CaPex required, low production cost and even tobacco not being a food or feed plant, which makes it inherently safe for large scale open field cultivation.”

Advanced mechanisms 
BioBetter’s plant bioreactors contain several advanced mechanisms designed to optimize performance and increase protein expression levels while making the plants containable and safe for large-scale, open-field cultivation. 

“These include induced expression, which allows us to control the onset of expression. This is important for several reasons, such as reduced silencing, separation of the expression stage from the plant growth stage and safety – plant expression does not occur without induction, preventing unwanted expression of the growth factors in undesirable contexts,” explains Yaari. 

In addition, the company engineers the plants to be sterile to avoid the escape of recombinant DNA into the ecosystem. “Another feature we use is a replicating vector system, that boosts protein expression level within a short time from induction,” he adds. 

Affordability and accessibility 
Helping cultivated meat companies offer affordable and accessible products to consumers, BioBetter is revolutionizing the future of cellular agriculture with its innovative molecular farming-based production platform. 

“Cultivated meat is still very expensive compared to conventional meat and the key is to reduce the growth medium costs to a minimum,” explains Yaari. 

“Our target is to reduce the production cost of growth factors, including insulin, a key part of the growth medium, to US$1 per gram, which is 100-fold less than the going rate today.”

The start-up has already achieved five milestones in the past year, including production scale-up/building pilot plan, commercial-scale cultivation of insulin- and FGF-expressing tobacco plants and reaching GF expression levels that significantly reduce production costs. 

New purposes for shunned tobacco
BioBetter discovered a new purpose for the traditionally shunned tobacco plants, transforming them into bioreactors for producing GFs. 

These GFs play a vital role in cultured meat cells’ proliferation and differentiation, allowing for the formation of authentic and well-structured muscle tissue.

These bioreactors will be grown in a large-scale, net-house cultivation system. 

The plants are carefully engineered to prevent the escape of any transgenic material. They are induced to express growth factors only when chemically triggered, and the company exclusively uses non-food, non-feed tobacco plants to eliminate any risk of inadvertent consumption or cross-contamination of food crops.BioBetter’s plant bioreactors contain several advanced mechanisms designed to optimize performance and increase protein expression levels. (Credit: Photographer, Rotem Golan)

A growing future?
The newly established pilot plant can process 100 kg of tobacco plant-derived GFs daily. It meets all regulatory requirements for producing food-grade growth factors, including FGF2 and insulin. 

It is seeking approval from the Ministry of Health for food manufacturing licensing. The company is committed to scalability, adhering to ISO2200 and HACCP standards.

“We more than doubled our workforce from 23 to 50 workers to advance all aspects of production, cultivation and R&D,” reports Yaari. 

“We stimulate the commercial aspirations of cultivated meat start-ups, and the pilot plant signifies a substantial step toward the company’s next growth stage in 2025: the capacity for processing 25 metric tons of leaves daily, reaching commercial production of five metric tons annually by the end of 2025.”

BioBetter also made breakthroughs in the cultivation of bovine insulin-expressing plants. Several thousand square meters of FGF2-expressing tobacco plants are already thriving in northern Israel. 

It’s the first time growth factor sources have been successfully planted in large net houses in four locations and with a fruitful harvest in its first season. Plans are underway to cultivate more FGF2 and insulin-expressing plants, with commercial roll-out projected for 2024.

“Over the past year, our outreach and collaborations expanded considerably,” adds Yarden. 

“We’ve shared GF samples with numerous cultivated meat companies and cell media producers worldwide and received promising proof-of-concept results for our FGF2 and insulin from several companies and academic laboratories.” The US$250 million global cultivated meat sector is poised for substantial growth, yet its realization hinges upon a significant supply of growth factors. 

In 2022, BioBetter secured US$10 million in a series A round investment led by Jerusalem Venture Partners. 

The company is also an active member of the Israeli Cultivated Meat Consortium, which unites academic institutions, large companies and start-ups to advance the field of cultivated meat collaboratively. 

By Elizabeth Green