Researchers have identified a previously unknown pyranose 2-oxidase enzyme from the wood-decaying fungus Punctularia strigosozonata and shown that, in laboratory cell cultures, it kills pancreatic carcinoma cells while also affecting a normal pancreatic cell line. The study, published in Frontiers in Molecular Biosciences, is an early-stage in vitro investigation, and the authors themselves describe the findings as preliminary evidence that the enzyme may serve as a candidate for further development rather than as a demonstrated cancer therapy.
Pyranose oxidase, or POx, is a FAD-dependent oxidoreductase that catalyzes the oxidation of D-glucose to 2-keto-D-glucose with the concomitant production of hydrogen peroxide. Although the enzyme has been well characterized in several fungi and bacteria, its potential relevance to cancer therapy had remained largely unexplored. The research team, led by Jiyang Guo of the Department of Oncology at the General Hospital of Northern Theater Command in Shenyang, China, discovered the new enzyme through gene mining and designated it PsPOx.
To obtain the enzyme in usable quantities, the researchers codon-optimized the gene, chemically synthesized it, and expressed it heterologously in Escherichia coli. The recombinant protein was then purified and subjected to biochemical characterization. Sequence alignment and structural modeling confirmed that PsPOx carries all the conserved features of the GMC oxidoreductase superfamily, the protein family to which pyranose oxidases belong.
Kinetic analysis revealed that PsPOx acts most efficiently on D-glucose among its tested substrates. The enzyme showed a catalytic efficiency, expressed as kcat/Km, of 85.09 mM⁻¹ s⁻¹ toward D-glucose, with a Km value of 0.8375 mM, which the authors interpret as indicating strong substrate affinity. These measurements establish the basic enzymatic profile of the new protein and confirm that it behaves as a functional pyranose 2-oxidase.
The central therapeutic question the team examined was whether PsPOx could kill pancreatic cancer cells. Using the CCK-8 assay, the researchers measured dose-dependent cytotoxicity against three human pancreatic carcinoma cell lines: PANC-1, AsPC-1, and BxPC-3. The half-maximal inhibitory concentration, or IC50, values were 257.8, 195.2, and 176.2 ng mL⁻¹, respectively, with BxPC-3 cells proving the most sensitive of the three cancer lines tested.
However, the selectivity data complicate any optimistic interpretation. The IC50 value for hTERT-HPNE, a normal human pancreatic epithelial cell line, was 195.6 ng mL⁻¹, which was comparable to the values observed for the AsPC-1 and BxPC-3 carcinoma lines. The authors state plainly that this indicates free PsPOx lacks selectivity between tumor and normal cells. In other words, in its unmodified form, the enzyme does not preferentially spare healthy pancreatic tissue in these culture conditions, a significant hurdle for any future therapeutic application.
To probe how the enzyme exerts its cytotoxic effects, the researchers carried out mechanistic studies in BxPC-3 cells. PsPOx treatment increased both intracellular and mitochondrial reactive oxygen species levels, a result consistent with the enzyme’s chemistry, since its reaction with glucose generates hydrogen peroxide.
The mechanistic work also showed that PsPOx treatment induced cell cycle arrest at the G0/G1 phase and triggered apoptosis in BxPC-3 cells. Consistent with the cell cycle arrest, the treatment downregulated the expression of Cyclin D1 and PCNA, two proteins involved in cell cycle progression and DNA synthesis. Together, these observations sketch a mechanism in which the enzyme’s hydrogen peroxide production drives oxidative stress, halts cell division, and pushes the cancer cells into programmed cell death.
The study’s scope deserves careful emphasis. All findings come from purified recombinant enzyme applied to cell lines in culture; no animal or human testing has been reported, and the enzyme’s delivery, stability, and behavior in a living organism remain unknown. The comparable sensitivity of the normal pancreatic cell line further underscores that a therapeutic window has not yet been demonstrated. For now, the work adds a newly characterized fungal enzyme to the small pool of oxidases examined for anticancer properties and provides a detailed in vitro baseline for future studies.
Subject of Research: A novel fungal pyranose 2-oxidase enzyme and its cytotoxic effects on pancreatic cancer cell lines in vitro
Article Title: Identification and characterization of a novel fungal pyranose 2-oxidase from the Punctularia strigosozonata with potent cytotoxicity against pancreatic carcinoma cell lines
Article References: Guo, J., Liu, J., Xu, L., Yan, T., & Zheng, Z. (2026). Identification and characterization of a novel fungal pyranose 2-oxidase from the Punctularia strigosozonata with potent cytotoxicity against pancreatic carcinoma cell lines. Frontiers in Molecular Biosciences, 13, 1914323. https://doi.org/10.3389/fmolb.2026.1914323
Image Credits: AI Generated
DOI: 10.3389/fmolb.2026.1914323
Keywords: pyranose oxidase, Punctularia strigosozonata, pancreatic cancer, cytotoxicity, reactive oxygen species, apoptosis, cell cycle arrest, enzyme kinetics, GMC oxidoreductase, in vitro study, hydrogen peroxide, gene mining
News Source: Nathaniel Bowman. (October 28, 2026). Newly Found Fungal Enzyme Shows Cytotoxicity Against Pancreatic Cancer Cells in Lab Tests. Scienmag.
