NSF Use-Inspired Acceleration of Protein Design (NSF USPRD)

NSF Use-Inspired Acceleration of Protein Design (NSF USPRD) is sponsored by U.S. National Science Foundation (NSF) Directorate for Technology, Innovation and Partnerships (NSF TIP). This initiative aims to accelerate the translation of artificial intelligence-based approaches to protein design, enabling new applications important to the U. S.

bioeconomy.

NSF invests nearly $32M to accelerate novel AI-driven approaches in protein design, strengthening the U.S. bioeconomy | NSF - U.S. National Science Foundation NSF invests nearly $32M to accelerate novel AI-driven approaches in protein design, strengthening the U.S. bioeconomy The U.S. National Science Foundation Directorate for Technology, Innovation and Partnerships (NSF TIP) announced an inaugural investment of nearly $32 million to five teams across the U.S. through the NSF Use-Inspired Acceleration of Protein Design (NSF USPRD) initiative.

This effort aims to accelerate the translation of artificial intelligence-based approaches to protein design and enable new applications of importance to the U.S. bioeconomy. "NSF is pleased to bring together experts from both industry and academia to confront and overcome barriers to the widespread adoption of AI-enabled protein design," said Erwin Gianchandani, NSF assistant director for TIP.

"Each of the five awardees will focus on developing novel approaches to translate protein design techniques into practical, market-ready solutions. These efforts aim to unlock new uses for this technology in biomanufacturing, advanced materials, and other critical industries. Simply put, NSF USPRD represents a strategic investment in maintaining American leadership in biotechnology at a time of intense global competition."

Researchers have made significant progress in predicting the 3D structures of proteins and are now leveraging this knowledge to design proteins with specific, desirable characteristics. These advances have been driven by macromolecular modeling, access to training data, applications of AI and machine learning, and high-throughput methods for protein characterization.

The NSF USPRD investment seeks to build on this foundation by bringing together cross-disciplinary and cross-sector experts nationwide. The goal is to extend these advances to enzyme design and accelerate the translation of this work into widespread, real-world applications.

Since its inception in 2022, NSF TIP has invested in initiatives that accelerate use-inspired and translational research and development to strengthen U.S. competitiveness in key technology areas. The USPRD initiative is one such effort, focused on advancing U.S. leadership in protein design and its commercial applications.

To support this goal, USPRD used an "Ideas Lab" approach, an interactive workshop that brings together experts and stakeholders with multiple perspectives to foster collaboration and spark innovation. Through this process, cross-sector teams from industry and academia co-developed innovative approaches to address challenges in biotechnology.

To identify an aggressive yet attainable practical set of use-driven activities, along with the supporting infrastructure and ecosystem needed to successfully implement them.

A summary of the awarded projects is outlined below: Arzeda Corp. — AI-designed Enzymes using Non-natural Cofactors for the Production of Bio-based Acrylates : By leveraging AI and advanced protein engineering, this project aims to transform the production of acrylates, costly molecules used in paints, Plexiglas® and super-absorbent materials.

The team will engineer enzymes to incorporate cost-efficient cofactor analogs to improve their stability and performance. The resulting scalable, cost-effective biocatalytic process can be readily expanded, potentially enabling affordable acrylate production. It also creates opportunities to make other important molecules that are hard to produce with current methods.

This project has the potential to accelerate the commercialization of advanced protein engineering, driving innovation and growth in the U.S. bioeconomy, with benefits for both industries and consumers. Koliber Biosciences Inc. — Transporters with Transformers : The team is addressing a key bottleneck in bioproduction: the inefficient transport of small molecules across cell membranes, which constrains microbial production systems.

By developing AI and machine learning tools to select and optimize cellular transporters, the project will enhance commercial outputs across the biomanufacturing industry. This advancement will help secure a stable supply of essential chemicals and expand applications in the food, agriculture, and energy sectors.

The outcome could be lower production costs of key components, and it will support a more resilient and competitive U.S. chemical supply chain that is better equipped to withstand disruptions.

Novozymes Inc. — Enabling Cell-free Synthesis of Longer Human Milk Oligosaccharides : This project aims to enable the production of complex human milk oligosaccharides (HMOs), nutrients essential to infant health and development that are difficult to produce.

Using advanced enzyme engineering, machine learning and cell-free protein synthesis, the team will develop and optimize tools for synthesizing longer, more biologically relevant HMOs. This work could lead to improved infant nutrition products and support the development of new enzyme systems with commercial properties for broader applications in human health and nutrition.

Purdue University — Programmable Small Molecule Biosynthesis : The team will develop bacteria to efficiently produce biodegradable and recyclable plastics that can withstand high temperatures, offering a sustainable alternative to conventional, unrecyclable plastics.

This innovation addresses challenges posed by unrecyclable plastics and has the potential to accelerate the future of biodesign by enabling the domestic manufacturing of high-performance, sustainable materials.

UC Santa Barbara — De Novo Design and Evolution of Enzymes for Biomass Upcycling to Surfactants and Fuels : By leveraging emerging AI-based methods to design effective enzymes and overcome challenges in biomass upcycling, this project aims to convert abundant plant materials into high-value products such as fuels, lubricants and surfactants.

In doing so, it seeks to advance sustainable biomanufacturing, expanding the economic potential of the bioeconomy through more efficient, scalable and cost-effective production methods. Learn more about TIP's work in emerging technologies. Directorate for Technology, Innovation and Partnerships (TIP)