Designer Yeast Turns Sugar Into 3-HP Making Biomanufacturing a Commercially Viable Reality

Scientists have taken a major step toward greener industrial chemistry by proving that a specially engineered yeast can produce 3-hydroxypropionic acid (3-HP) efficiently, affordably, and at a scale that finally makes commercial biomanufacturing realistic. This matters because 3-HP is a critical building block for acrylic acid, a chemical that quietly powers a huge range of everyday products—from disposable diapers and water-based paints to fabric coatings, sealants, fertilizers, and soil treatments.

Until now, acrylic acid and its precursor 3-HP have been made almost entirely from petroleum, using energy-intensive chemical processes with a large carbon footprint. While scientists have known for years that microbes could theoretically make 3-HP from renewable plant sugars, the economics never worked out. Yields were too low, concentrations were too weak, and downstream processing was too expensive.

That barrier may now be falling.

In a new study led by researchers from the University of Illinois Urbana-Champaign and Penn State University, scientists developed a high-performance yeast strain that can convert sugar into 3-HP at levels that exceed long-standing benchmarks for commercial viability. The work was carried out under the Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), a U.S. Department of Energy–funded Bioenergy Research Center, and the results were published in Nature Communications.

At the center of this breakthrough is a tiny but powerful organism: Issatchenkia orientalis, an acid-tolerant yeast that thrives in harsh, low-pH environments. Unlike many commonly used microbes, this yeast can survive and function efficiently in acidic conditions, which turns out to be a major advantage for industrial biomanufacturing.

Why 3-HP Is Such a Big Deal

3-hydroxypropionic acid is considered a platform chemical, meaning it can be converted into many other valuable compounds. Its most important downstream product is acrylic acid, a chemical with an estimated $20 billion global market. In 2019 alone, worldwide demand for acrylic acid reached about 6.6 million tons, and demand continues to grow.

Acrylic acid gives disposable diapers their absorbency, improves stain resistance in textiles, strengthens paints and coatings against weather damage, and enhances the performance of agricultural products. Beyond acrylic acid, 3-HP can also be upgraded into chemicals like malonic acid, which is used in pharmaceuticals, vitamins, biodegradable plastics, and agrochemicals.

From an environmental perspective, replacing petroleum-based 3-HP with a bio-based alternative could significantly reduce greenhouse gas emissions while creating new markets for agricultural feedstocks such as corn-derived glucose.

Why Previous Bio-Based Approaches Fell Short

Commercial producers—including large companies and biotech startups—have spent decades trying to crack bio-based 3-HP production. The challenge has always been the same: microbes simply didn’t make enough of the chemical, or they required conditions that drove costs sky-high.

Two factors matter most in fermentation-based manufacturing: yield (how much product is made from a given amount of sugar) and titer (how concentrated the product becomes). Earlier microbial systems struggled on both fronts. Many also required fermentation at neutral pH, which meant constant chemical buffering and expensive downstream recovery steps.

These limitations kept bio-based 3-HP from competing with fossil-derived methods.

How Acid-Tolerant Yeast Changed the Equation

The CABBI team approached the problem differently by choosing Issatchenkia orientalis as their microbial host. This yeast naturally tolerates acidic environments, which simplifies processing and reduces costs by eliminating the need for pH neutralization during fermentation.

Using a genetic toolbox previously developed for this organism, the researchers systematically re-engineered its metabolism to push more carbon toward 3-HP production. A key step was identifying the beta-alanine pathway as the most efficient route. Genome-scale metabolic modeling showed that this pathway offered the highest theoretical yield while requiring less oxygen than alternatives—an important consideration for industrial fermenters.

The team then identified three highly productive gene variants within this pathway that dramatically improved efficiency. One crucial enzyme, known as PAND, plays a central role in 3-HP biosynthesis. By integrating multiple copies of the PAND enzyme into the yeast’s genome, researchers significantly boosted production. Additional metabolic engineering strategies further improved both yield and titer.

Record-Setting Performance at Lab Scale

When the engineered yeast was tested in fed-batch fermentation over a seven-day period, the results were striking. The process achieved an overall yield of 0.7 grams of 3-HP per gram of glucose, equivalent to a 70 percent conversion rate, along with a titer of 92 grams of 3-HP per liter.

These numbers exceed thresholds previously identified as necessary for commercial viability and, according to the researchers, represent the highest reported yield and titer for 3-HP production among all engineered bacteria and yeast hosts to date.

Proving the Economics and Environmental Benefits

High lab performance alone isn’t enough to justify industrial adoption, so the team went a step further. Using BioSTEAM, a process-simulation platform developed through CABBI, researchers modeled a full biomanufacturing facility that converts sugar into 3-HP and then upgrades it into acrylic acid.

They conducted both a techno-economic analysis (TEA) and a life cycle assessment (LCA) to evaluate financial feasibility and environmental impact. The results showed that the process is financially viable and offers meaningful sustainability advantages compared with petroleum-based acrylic acid production.

This modeling work confirms that the yeast-based process isn’t just scientifically impressive—it makes economic sense at industrial scale.

What Comes Next for This Technology

With proof of concept established, the researchers are now focused on scaling up the process, integrating downstream purification steps, and testing additional renewable feedstocks beyond glucose to further improve economics.

Other CABBI scientists are also exploring new applications for the 3-HP produced using this method. One effort involves converting the fermentation broth into malonic acid, opening doors to new markets in pharmaceuticals and biodegradable materials.

Together, these projects position Issatchenkia orientalis as a next-generation microbial platform for sustainable chemical manufacturing.

A Bigger Picture for Biomanufacturing

This study highlights how advances in metabolic engineering, systems biology, and process modeling are finally converging to make biomanufacturing competitive with traditional petrochemistry. Instead of simply replacing fossil inputs, these approaches create entirely new value chains rooted in agriculture and renewable resources.

If adopted at scale, technologies like this could reshape how everyday chemicals are made—quietly improving sustainability while keeping costs in check.

Research paper:
https://www.nature.com/articles/s41467-025-67621-8