Commercially viable biomanufacturing: designer yeast turns sugar into lucrative chemical 3-HP

(Press-News.org) Using a tiny, acid-tolerant yeast, scientists have demonstrated a cost-effective way to make disposable diapers, microplastics, and acrylic paint more sustainable through biomanufacturing.

A key ingredient in those everyday products is acrylic acid, an important industrial chemical that gives disposable diapers their absorbency, makes water-based paints and sealants more weather-proof, improves stain resistance in fabric, and enhances fertilizers and soil treatments.

Acrylic acid is converted from a precursor called 3-Hydroxypropanoic acid, or 3-HP, which is made almost exclusively from petroleum through chemical synthesis — an energy-intensive process. But 3-HP can also be produced from renewable plant material by using engineered microbes to ferment plant sugars into this high-value chemical. Until now, however, the biomanufacturing process has not proven profitable.

In a new study, scientists at the University of Illinois Urbana-Champaign and Penn State University developed a cost-effective, bio-based method to produce 3-HP and validated its commercial potential for this lucrative market.

Their new paper in Nature Communications reports on the development of a high-yield strain of Issatchenkia orientalis yeast for 3-HP production, as well as extensive techno-economic analysis and life cycle assessment that demonstrated its commercial viability and environmental benefits. The scientists are all part of the Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), a U.S. Department of Energy (DOE) Bioenergy Research Center, which funded the research.

“The high-level production of this chemical from yeast can provide a pathway to acrylic acid production, significantly boosting the agricultural economy,” said CABBI Conversion Theme Lead Huimin Zhao, a lead author on the study and Professor in the Department of Chemical and Biomolecular Engineering (ChBE) and the Carl R. Woese Institute for Genomic Biology (IGB) at Illinois

According to DOE, the commercial potential for 3-HP is huge: The acrylic acid market alone is estimated at $20 billion, with global demand of approximately 6.6 million tons in 2019. And 3-HP can be converted to other valuable industrial chemicals.

Commercial producers — from large companies like BASF and Cargill to smaller biotechnology firms — have been working for decades on bio-based production of 3-HP using various bacteria and yeasts, Zhao said. The problem is that both the amount of 3-HP produced from a given amount of substrate like glucose (yield) and the concentration (titer) have remained very low.

The CABBI scientists tackled this challenge in several ways. They chose I. orientalis for the fermentation process, a yeast that thrives in a low pH acidic environment and has been used to produce other organic acids. That simplified processing by eliminating costly steps required by other yeasts or bacteria that need a neutral, higher-pH environment. 

The team also employed unique metabolic engineering strategies to boost 3-HP production in the yeast, using a genetic toolbox they had previously developed for I. orientalis. First, researchers identified a genetic pathway known as beta-alanine as the optimal target. Genome-scale modeling by Costas Maranas, Professor of Chemical Engineering at Penn State, showed that it offered the highest theoretical yield and required the least oxygen.

Next researchers found three highly productive gene variants from the beta-alanine pathway that significantly improved efficiency. Co-author Teresa Martin, research coordinator in Zhao’s lab, discovered an active enzyme in 3-HP biosynthesis known as PAND. Harry (Shih-I) Tan, a Postdoctoral Researcher in Zhao’s lab and first author on the study, integrated multiple copies of the PAND enzyme into a new strain of I. orientalis, which boosted 3-HP production. The team then applied other novel engineering strategies to further increase the titer and yield.

Scaling up to lab-level fermentation — where yeasts are fed sugars in batches over seven days — the researchers achieved an overall yield of 0.7 grams of 3-HP per gram of glucose consumed (0.7 g/g), or 70 percent; and a titer of 92 grams of 3-HP per liter. The results exceeded the thresholds for commercial viability laid out in previous studies.

“To the best of our knowledge, our study represents the highest reported yield and titer for 3-HP production among all engineered bacteria and yeast hosts,” Zhao said.

Using the BioSTEAM software developed through CABBI, Professor Jeremy Guest and Postdoctoral Researcher Sarang Bhagwat of the Department of Civil and Environmental Engineering at Illinois then simulated a biomanufacturing facility to produce 3-HP using the new process and then upgrade it to acrylic acid, and evaluated its financial feasibility and environmental benefits through techno-economic analysis (TEA) and life cycle assessment (LCA). Their work showed the process is financially viable for bio-based acrylic acid production.

“This work establishes I. orientalis as a next-generation platform for cost-effective 3-HP production and paves the way toward industrial commercialization,” Zhao said.

The researchers are now working with other CABBI scientists at Illinois to scale up the process, integrate downstream processing, and incorporate other renewable feedstocks to enhance its economic feasibility.

Meanwhile, CABBI researchers are working on other 3-HP applications as part of the center’s mission to generate value-added chemicals from plants. George Huber, Professor of Chemical and Biological Engineering at the University of Wisconsin-Madison, is incorporating the 3-HP broth from this study into a streamlined chemical process to convert it into malonic acid – an important industrial chemical used to produce vitamins and other pharmaceuticals, biodegradable plastics, and agrochemicals.

Other CABBI co-authors on this study included Patrick Suthers of Penn State; and Vinh Tran, Wuying Tang, and Zia Fatma of ChBE and IGB.

The paper, “High yield production of 3-hydroxypropionic acid using Issatchenkia orientalis,” is available at doi.org/10.1038/s41467-025-67621-8.

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