NSF awards Novonesis funding to advance cell-free biomanufacturing of human milk oligosaccharides

DAVIS, California, U.S. – September 17, 2025. The U.S. National Science Foundation (NSF) has awarded Novonesis funding through its Use-Inspired Acceleration of Protein Design (NSF USPRD) initiative for "Enabling cell-free synthesis of longer human milk oligosaccharides (HMOs)." The award is part of the NSF Directorate for Technology, Innovation and Partnerships' (NSF TIP) nearly $32 million investment announced August 7, 2025, to accelerate novel, AI-driven approaches in protein design. The effort aims to develop cost-effective methods for producing complex nutrients found in human breast milk—nutrients that are vital to infant health and development yet remain scarce in today's infant formulas.

USPRD, managed by NSF TIP, brings together industry–academic teams via an Ideas Lab – a one-week brainstorming session with invited experts from industry, academia, and other sectors – to translate AI-enabled protein design into practical, market-ready solutions. The USPRD initiative is designed to secure U.S. leadership in biotechnology by accelerating innovation to bring sustainable bio-based products to market in a highly competitive global landscape.

Expanding Access to Complex Human Milk Oligosaccharides

HMOs are complex sugars that play a vital role in early-life immunity, brain development, and long-term health. While infant formulas contain only a fraction of the simplest HMOs, the Novonesis-led project aims to enable large-scale, affordable synthesis of longer, more complex HMOs through advanced enzyme engineering and computational design.

The project brings together experts from Novonesis, Stanford University, and UC Davis to:

•    Design specialized enzymes that can create longer, more complex human milk sugars (HMOs).
•    Use advanced artificial intelligence tools to speed up the process of predicting and improving enzyme performance.
•    Test enzymes in cell-free systems—platforms that work outside of living cells—to quickly screen and refine new ideas.
•    Evaluate real-world potential by ensuring the methods can be scaled up and remain cost-effective in industrial settings.

This initiative not only addresses critical gaps in infant nutrition but also contributes broadly to the protein design community by developing reusable models, new design algorithms, and openly shared datasets.  These innovations will not only accelerate HMO research but also pave the way for broader applications in synthetic biology, enabling a new generation of AI-driven breakthroughs in enzyme and protein design, and pioneering new pathways in biomanufacturing.

In a separate NSF TIP program, NSF Advancing Cell-Free Systems Toward Increased Range of Use-Inspired Applications, which also employed the Ideas Lab approach, Novonesis will participate as a sub awardee on "Electricity-Driven Cell-Free Cascades." By coupling biology with clean energy, researchers aim to convert carbon dioxide (CO₂)—a stable waste gas—into methanol, a critical fuel and chemical feedstock. This electricity-driven biology could achieve far higher efficiencies than current methods, establish a scalable and commercially viable platform for carbon utilization, and reduce industrial dependence on fossil resources. In doing so, it not only advances scientific discovery but also offers a powerful tool for building a sustainable, next-generation biomanufacturing sector.

"These NSF awards highlight Novonesis' leadership in developing innovative biosolutions that address human health and sustainability challenges," said Tue Micheelsen, President of Novonesis North America & Head of Global Consumer Health. "I am especially proud of the impact our teams are having across the country. At Novonesis, we believe in using the power of biology to solve real-life challenges. This funding from NSF underscores both the promise of our science and the results our people can deliver for people and planet."