Engineered Enzyme Converts Formaldehyde to Valuable Chemical

Chonnam National University, The Research Information Management Team, Office of Research Promotion

Formaldehyde is a common chemical used in various industries as a disinfectant, resin precursor, and synthetic intermediate. It is volatile, highly toxic, and a key environmental pollutant with genotoxic and carcinogenic effects, harming both human health and the environment. Therefore, there is an urgent need to come up with useful strategies to convert formaldehyde into non-toxic value-added products, ensuring environmental protection as well as chemical sustainability.

In a recent breakthrough, a team of researchers from the Republic of Korea, including Dr. Taner Duysak, the leading first author of this paper and a researcher in the group led by Professor Jeong-Sun Kim at the Department of Chemistry and the Host-Directed Antiviral Research Center, Chonnam National University, has developed an innovative biocatalytic cascade for the selective enzymatic conversion of formaldehyde into enantiopure L-glyceraldehyde—a high-value chiral C3 compound. Their novel findings were made available online on 21 October 2025 and have now been published in the International Journal of Biological Macromolecules on 1 November 2025.

The team utilized a structurally engineered fructose-6-phosphate aldolase (GaFSA) derived from Gilliamella apicola. This compound catalyzes carbon–carbon bond formation through an aldol condensation reaction between glycolaldehyde (GALD) and formaldehyde. However, this approach led to the formation of a significant amount of D-threose as a byproduct. Notably, structure-guided mutagenesis via Ser166 and Val203—key determinants of regioselectivity—lowered D-threose formation with over 93% selectivity under mild aqueous conditions.

Furthermore, the researchers also achieved in situ GALD production from formaldehyde and thereby mitigated external GALD supplementation by coupling engineered GaFSA to an optimized glyoxylate carboligase from E. coli (EcGCL). "This one-pot, eco-friendly, and scalable enzymatic cascade reached a conversion efficiency of about 94% from 25 mM formaldehyde at pH 7.5 and 40 °C, with minimal byproducts. The reaction proceeds entirely in water, under ambient pressure, without toxic reagents or organic solvents, requiring only natural cofactors for EcGCL activity," points out Dr. Duysak.

The present research thus shows how a dangerous industrial toxin, formaldehyde, can be transformed into a safe and valuable chemical, L-glyceraldehyde, using an engineered enzyme. This demonstrates how enzyme engineering, such as amino acid mutation, can turn pollution into useful building blocks for medicine and industry.

Dr. Duysak highlights the potential applications of their work. "It promotes not only environmental detoxification in the form of the safe removal of formaldehyde from industrial waste streams but also green chemistry. L-glyceraldehyde is a renewable raw material that serves as a crucial precursor for rare sugars such as L-sorbose and L-psicose and chiral intermediates used in drug development. As a C3 compound, it is a key player in many biochemical pathways. L-glyceraldehyde can facilitate the development of novel compounds with antibiotic, anti-cancer, and other therapeutic effects."

In the next decade, approaches similar to this study could help industries detoxify hazardous chemicals while creating useful compounds, enable circular chemical processes where waste is recycled into new materials, support the development of eco‑friendly pharmaceuticals and specialty chemicals, as well as inspire broader adoption of biocatalytic cascades for sustainable chemical manufacturing worldwide.

About the institute

Chonnam National University (CNU), established in 1952 as Korea's first national university, is a leading institution of higher learning located in Gwangju and South Jeolla Province. Building on its founding commitment to cultivating leaders of integrity and professional excellence, CNU contributes to national development and global progress through the pursuit of knowledge, ethical responsibility, and inclusive excellence. Guided by the core motto "Truth, Creativity, and Service," the university advances research, education, and public engagement that strengthen resilient societies, foster sustainable development, and promote the well-being of future generations. As a trusted partner in the global community, CNU remains dedicated to addressing complex challenges in an increasingly interconnected world.

Website: https://global.jnu.ac.kr/jnumain_en.aspx

About the author

Dr. Taner Duysak, the leading first author of this paper, is a researcher at the Department of Chemistry and the Host-Directed Antiviral Research Center, Chonnam National University, Republic of Korea. The group led by Prof. Jeong-Sun Kim focuses on enzyme engineering and sustainable biocatalysis, turning toxic industrial chemicals into safe, high-value products using engineered enzymes. Their recent research demonstrated how mutations in fructose-6-phosphate aldolase can selectively convert formaldehyde into L-glyceraldehyde, a valuable chiral building block. Their broader goal is to develop green biocatalytic platforms that support environmental protection and sustainable chemical manufacturing.

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