Innovations in HMO Production: Can Plants Outperform Microbes?

In recent years, several companies have turned to microbes for the production of high-value human milk oligosaccharides (HMOs) for infant formula. However, a compelling question arises: Could plants serve as a better production vehicle?

AgFunderNews (AFN) recently engaged with Totality Biosciences‘ co-founder and CEO, Dr. Leila Strickland (LS), alongside VP of R&D, Dr. Collin Barnum (CB), at the Future Food-Tech conference in San Francisco. They shared insights on the limitations of microbial HMO production, the promise of plant-based alternatives, and how this innovative approach may broaden the availability and affordability of HMOs.

Understanding HMOs and Their Importance in Infant Formula

AFN: What are HMOs, and why are they significant for infant formula companies?

LS: Human milk oligosaccharides (HMOs) comprise a specialized group of complex carbohydrates found exclusively in breast milk. These unique molecules play a critical role in early immune system development, gut health, and can even modulate allergic responses. Parents naturally desire formulas that mirror the nutritional composition of breast milk, making HMOs an essential ingredient for infant formula, especially in situations where breastfeeding isn’t possible.

Broadening the HMO Market Beyond Infants

AFN: Is there potential for HMOs beyond infant formula?

LS: Absolutely. Large food and health companies are exploring the application of HMOs for various age groups. They are not only interested in premium infant formulas but are also looking into pediatric nutrition and even products intended for adults. There’s significant interest in reducing the high costs associated with HMO ingredients to facilitate a broader market application.

Limitations of Current HMO Production Methods

AFN: Currently, how are most HMOs produced?

LS: At present, a limited number of HMOs are produced via microbial fermentation, primarily using genetically engineered E. coli that synthesize these complex sugars. Unfortunately, this method is both cost-prohibitive and limited in scale, yielding only a handful of the hundreds of oligosaccharides present in human milk.

The Case for Plants as a Production Platform

AFN: What makes plants a more favorable option for HMO production?

CB: Plants are inherently proficient at producing sugars, making them an ideal chassis for HMO synthesis. Furthermore, agriculture operates on a scale unmatched by microbial or animal cell systems, enabling us to produce HMOs at a lower cost while also expanding the diversity of oligosaccharides we can create.

Production Strategies and Plant Selection

AFN: What specific plants are you targeting for HMO production, and why?

CB: We utilize two primary strategies: a lab-scale platform for rapid genetic testing and large-scale production plants. Our initial focus is on soybean due to its established agricultural infrastructure and high yield potential.

Research and Development in HMO Production

AFN: Are you using specific plants for lab testing?

CB: Yes, we initially utilize transient expression systems such as tobacco plants for R&D purposes. While not feasible for large-scale commercial use, they serve as a valuable testing ground before we transition to larger agricultural production.

Economic Viability and Future Outlook

AFN: How do you plan to monetize the entire soybean and ensure supply chain stability?

LS: We’re designing our business model around existing systems to facilitate the monetization of the entire soybean, not just the high-value carbohydrate fraction. This will include selling oil and protein concentrates for varied nutritional applications.

Identifying Key HMOs for Production

AFN: Do we know which HMOs are most critical?

LS: Surprisingly, our understanding of human milk’s molecular structure is still evolving; current R&D libraries represent only about 25% of the total structures known to exist. This implies that there are numerous unexplored HMOs that could be significant for infant health.

Targeted HMO Production Goals

AFN: What HMOs do you intend to prioritize?

LS: Initially, we’re focusing on 2′ FL, one of the simpler HMOs to produce, as well as DSLNT (Disialyllacto-N-tetraose). The latter holds particular significance as it is currently out of reach for existing production technologies yet shows incredible promise for supporting premature infants in NICUs.

Conclusion

The shift from microbial to plant-based production of HMOs could revolutionize infant nutrition, enhancing product availability and affordability. With ongoing research and innovative approaches, companies like Totality Biosciences are poised to make significant strides in this critical area of food technology.

Further Reading

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