Researchers engineered enzymes to convert toxic formaldehyde into valuable L-glyceraldehyde, advancing green chemistry, pollution detoxification, and sustainable chemical manufacturing.
Formaldehyde is a widely used industrial chemical, valued for its role as a disinfectant, resin precursor, and intermediate in numerous synthetic processes. Despite its versatility, formaldehyde poses severe risks due to its volatility and high toxicity. It is a well-established environmental pollutant with genotoxic and carcinogenic properties, posing serious threats to both human health and ecosystems. As industrial usage continues globally, the challenge of managing and neutralizing formaldehyde waste has become increasingly urgent. Scientists and environmental engineers are therefore seeking innovative methods to convert this hazardous compound into safer, value-added materials that support sustainability and circular chemistry.
In a major scientific advance, researchers from the Republic of Korea at Chonnam National University have developed a novel enzymatic strategy that transforms toxic formaldehyde into a high-value chemical building block. The research was led by Dr. Taner Duysak, the study’s first author, working under Professor Jeong-Sun Kim at the Department of Chemistry and the Host-Directed Antiviral Research Center. The findings were first made available online on 21 October 2025 and were formally published on 1 November 2025 in the International Journal of Biological Macromolecules.
The team designed an advanced biocatalytic cascade capable of selectively converting formaldehyde into enantiopure L-glyceraldehyde, a chiral C3 molecule with significant industrial and pharmaceutical value. Central to this achievement was the use of a structurally engineered fructose-6-phosphate aldolase known as GaFSA, originally derived from Gilliamella apicola. This enzyme catalyzes carbon-carbon bond formation through an aldol condensation reaction between formaldehyde and glycolaldehyde (GALD). While the native reaction pathway produced unwanted D-threose byproducts, the researchers employed structure-guided mutagenesis to overcome this limitation.
By modifying two critical amino acid residues-Ser166 and Val203-the team significantly improved the enzyme’s regioselectivity. These precise mutations reduced D-threose formation and achieved over 93% selectivity toward the desired L-glyceraldehyde under mild, aqueous conditions. This level of control demonstrates how enzyme engineering can fine-tune catalytic performance to favor specific products.
To further enhance sustainability, the researchers eliminated the need for externally supplied glycolaldehyde by generating it directly from formaldehyde within the same reaction system. This was accomplished by coupling the engineered GaFSA with an optimized glyoxylate carboligase derived from Escherichia coli. The resulting one-pot enzymatic cascade proved highly efficient, achieving approximately 94% conversion from 25 mM formaldehyde at pH 7.5 and 40 °C. Importantly, the process operates entirely in water, under ambient pressure, without toxic reagents or organic solvents, relying only on natural cofactors.
According to Dr. Duysak, this environmentally benign approach demonstrates how industrial toxins can be repurposed into valuable chemical resources. Beyond detoxifying waste streams, the method supports green chemistry by producing L-glyceraldehyde, a renewable precursor for rare sugars such as L-sorbose and L-psicose, as well as chiral intermediates used in drug synthesis. As a fundamental C3 compound, L-glyceraldehyde plays an essential role in numerous biochemical pathways and can support the development of antibiotics, anticancer agents, and other therapeutic molecules.
Looking ahead, similar biocatalytic strategies could enable industries to neutralize hazardous pollutants while simultaneously generating commercially useful compounds. Such approaches may accelerate circular chemical manufacturing, promote eco-friendly pharmaceutical development, and inspire wider adoption of enzyme-based cascades for sustainable industrial chemistry worldwide.
