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By Agroempresario.com
In a world increasingly affected by unpredictable weather patterns, political instability, and diseases, the botanical supply chain faces growing vulnerabilities. Krokos Bio, a California-based biotechnology startup, is leveraging plant cell culture technology to mitigate these challenges and secure a stable supply of high-value botanicals, with a focus on saffron production. Founded in mid-2024 by Jacob Lang, Krokos Bio is tackling the precarious global saffron supply by utilizing a biotechnological approach to grow saffron’s key bioactives in controlled lab conditions.
The company recently secured funding from Big Idea Ventures, a leading player in the sustainable food and ingredient sectors. With this backing, Krokos Bio is positioned to offer a game-changing solution for producing saffron – one of the world’s most expensive and sought-after spices.
Saffron, derived from the stigmas of the Crocus sativus plant, is highly prized for its vibrant red-orange color, unique flavor, and exorbitant price tag, often reaching up to $1,000 per kilogram. However, the production of saffron is fraught with challenges. A significant portion of the world’s saffron is produced in Iran, a region frequently affected by drought and climate volatility, impacting both the quality and availability of the spice. This is where Krokos Bio sees an opportunity: plant cell culture.
Jacob Lang, who has a background in bioprocess development with microbial and animal cells, founded Krokos Bio after recognizing the potential of plant cell culture in addressing issues within high-value botanical industries. Lang noted, “I started reading about the drought in Iran, where the majority of the world’s saffron is produced, and the impact it was having on prices. That was the tipping point for me. It seemed like a great application for plant cell culture technology.”
Instead of traditional farming techniques that rely on sunlight, water, and soil, plant cell culture uses bioreactors to grow plant cells in a controlled environment. This method allows for the production of specific bioactives, such as those found in saffron – compounds like crocin, picrocrocin, and safranal, responsible for the spice’s distinctive color, flavor, and aroma. The goal is not just to replicate the traditional farming process but to ensure a stable, consistent supply of these valuable botanicals, even in the face of climate shocks and other disruptions.
To produce saffron through plant cell culture, Krokos Bio takes samples from source plants and de-differentiates them – essentially returning the cells to a stem cell-like state. From this point, the cells are cultured to form a callus culture, an undifferentiated mass of cells that can then rapidly reproduce and divide in a liquid suspension culture.
Lang explained, “Our platform incorporates a modification to the normal workflow, which significantly enhances the yield and reduces the R&D timeline. A lot of plant cell culture work traditionally focuses on strain development due to the challenge of low productivity in plant cells, but our approach aims to overcome these limitations.”
Once the cells grow in sufficient quantity, they are re-differentiated into the stigma cells necessary for saffron production. The process promises higher yields and accelerated timelines, making it economically viable to scale production. Lang also added, “We’re focusing on developing a food-grade saffron powder, which will contain all three key compounds – crocin, picrocrocin, and safranal – and will be suitable for culinary uses.”
The high cost of saffron makes it an ideal target for plant cell culture, as even small-scale production can yield favorable unit economics. Lang noted, “The unit economics of saffron production using plant cell culture look promising, even at relatively small-scale operations. We’re optimistic that it will be viable at pilot scale of around 1,000 liters, which is exciting from a commercial perspective.”
Krokos Bio’s approach to bioreactor design and materials also contributes to the cost-effectiveness of its technology. Lang revealed, “We’re looking at a variety of materials for bioreactors, including plastics and even repurposed brewing equipment. This helps keep costs down and makes the process more scalable without relying on expensive biopharma equipment.”
As Krokos Bio navigates the plant cell culture space, strategic partnerships are essential for scaling operations. Lang highlighted that co-manufacturers with expertise in plant cell culture are becoming more prevalent across North America, Europe, and South America. However, there’s still a shortage of companies with the capability to scale up the technology. Krokos Bio plans to partner with these co-manufacturers to bring its product to market efficiently.
Moreover, the growing interest in bioactives and alternative production methods from major industry players like Mondelēz, Barry Callebaut, Lindt, Meiji, and others will help foster further development of the plant cell culture industry. These companies have either invested directly or engaged in incubators with plant cell culture startups, indicating a rising demand for this innovative technology.
Lang emphasized that working with established ingredient companies and distributors will be crucial to Krokos Bio’s business model. He said, “It will make sense to partner with companies that already understand the market and have established relationships with consumers, ensuring we reach the right markets in an efficient manner.”
Despite the promising potential of plant cell culture for saffron and other high-value botanicals, Krokos Bio faces several challenges in scaling the technology. One significant hurdle is the development of healthy, stable calluses, as plant cells are often shear sensitive and require precise conditions for optimal growth. Lang acknowledged that there are “a million opinions on how to go about it,” but he is confident that Krokos Bio’s modified platform will overcome these obstacles.
Lang also pointed out that careful attention to the bioprocess is necessary to optimize the production of saffron’s bioactive compounds. “There are many levers you can pull in the bioprocess,” he explained. “By adjusting the temperature, pH, oxygen levels, and the components of the growth medium, we can encourage the cells to produce high yields of the compounds we want.”
Krokos Bio’s approach to saffron production is just the beginning. The broader potential for plant cell culture to revolutionize the production of botanicals and other valuable crops is vast. As supply chains become increasingly disrupted by climate change, political instability, and disease, plant cell culture offers a scalable, sustainable solution that could reshape the future of the global botanical industry.
Lang concluded, “There’s a lot of potential in plant cell culture for high-value botanicals, and we’re excited about the future. As we continue to refine our processes and expand our partnerships, we’re looking forward to playing a major role in stabilizing the supply chains for these critical ingredients.”
