Fungus Found on Almonds Yields a Cocktail of Drug-Like Molecules

A fungus scraped from the surface of dried almonds has turned out to be one of the more chemically generous microbes described in recent years. Researchers in Algeria and Tunisia isolated a strain designated PB1 from the nuts, identified it by both its microscopic architecture and its DNA as Penicillium citrinum, and then put its chemistry through an unusually broad battery of pharmacological tests. The results, published in the journal 3 Biotech, show that a single crude extract from this mold can inhibit pathogenic bacteria at remarkably low concentrations, dampen inflammatory enzymes, block a key digestive enzyme linked to diabetes, and suppress the proliferation of cancer cells in vitro. The work adds to a growing body of evidence that the fungi living quietly on everyday foods are not merely spoilage organisms but underexplored pharmaceutical factories.

The team, led by Dounya Achwak Chemmam of the University of Jijel, grew the fungus for twenty-one days and extracted its metabolic products with ethyl acetate, a solvent chosen for its ability to pull moderately polar organic molecules out of fungal biomass. When that crude extract was tested against a panel of pathogenic microorganisms, the numbers were striking. The minimum inhibitory concentration, or MIC, the lowest dose that halts visible microbial growth, was just 7.5 micrograms per milliliter against Staphylococcus aureus ATCC 43300 and 15 micrograms per milliliter against Bacillus cereus ATCC 14579. For a raw, unfractionated extract, those values are competitive with many purified natural-product antibiotics and suggest that the active constituents are present at meaningful levels rather than as trace contaminants.

Antibacterial potency was only the beginning. The same extract showed an IC50 of 33.27 micrograms per milliliter in an anti-inflammatory assay, meaning that half of the measured inflammatory activity was suppressed at that concentration. In an antidiabetic screen targeting enzymes that break down dietary sugars, the extract achieved an IC50 of just 3.32 micrograms per milliliter, an exceptionally low figure that points to strong inhibition of carbohydrate-hydrolyzing enzymes. Inhibiting these enzymes is a validated strategy for managing blood glucose spikes after meals, and fungal metabolites have increasingly been flagged as alternatives to synthetic drugs such as acarbose. Finally, the extract exhibited antiproliferative activity with an IC50 of 124.16 micrograms per milliliter against the tested cell line, a more modest but still noteworthy effect that rounds out the pharmacological profile.

Because the activity of a fungal extract depends heavily on how the organism is grown, the researchers next turned to fermentation optimization using the one-factor-at-a-time method, systematically varying culture conditions to find the settings that maximize antimicrobial output. The tuned conditions produced dramatic gains. Against Escherichia coli, the optimized cultures generated a zone of inhibition of 19 millimeters; against Klebsiella pneumoniae, 23 millimeters; and against Bacillus cereus, an impressive 34 millimeters. That last figure is particularly significant because Bacillus cereus is a spore-forming foodborne pathogen, and activity of that magnitude against it suggests the extract could have applications well beyond the clinic, including food preservation and agricultural biocontrol.

What exactly is inside the extract? To answer that, the team deployed two complementary analytical techniques. Gas chromatography coupled to mass spectrometry, or GC-MS, separates volatile and semi-volatile compounds and fragments them into characteristic mass fingerprints that can be matched against spectral libraries. High-performance liquid chromatography, or HPLC, handles compounds that are less volatile or more thermally fragile. Together, the two methods revealed fourteen distinct metabolites produced by PB1, a chemically diverse roster that includes small organic acids, sugars, and more exotic structures.

The identified compounds read like a short course in fungal chemistry. Among them are 3-methylbutanoic acid and propanoic acid, short-chain fatty acids with documented antimicrobial effects against oral and other pathogens; ethylene glycol and 2,3-butanediol, small alcohols whose antibacterial properties have only recently attracted attention; and lactic acid alongside 2,3-dihydroxy-3-methylpropanoic acid, both hydroxy acids that can disrupt microbial membranes. The list also contains phosphorylated and siloxane-containing species, the sugars D-fructofuranose pentakis and D-psicofuranose pentakis, the plant-like glycoside erigeside B, D-galactonic acid, a bufadienolide-type steroid called bufa-20,22-dienolide, and the nucleoside uridine, a molecule that has inspired synthetic small-molecule inhibitors in medicinal chemistry.

No single one of these compounds may account for the full spectrum of activity on its own. More likely, the extract works through additive or synergistic interactions, a common feature of crude natural-product mixtures that pharmaceutical chemists are only beginning to exploit systematically. The presence of short-chain fatty acids could underpin much of the antibacterial effect, while the glycosides and the bufadienolide are plausible contributors to the cytotoxic and enzyme-inhibiting activities. Disentangling those contributions, through bioassay-guided fractionation, will be the essential next step before any clinical relevance can be claimed.

Context matters for this discovery. Penicillium citrinum is a species with a storied double reputation. On one hand, it is the original source of mevastatin, the first statin cholesterol-lowering drug, and its relatives have given medicine compounds ranging from antibiotics to immunosuppressants. On the other hand, the species is known for citrinin, a mycotoxin that contaminates grains and other foods, which means any future development of PB1-derived products would need careful toxicological scrutiny. The current study did not report citrinin among the fourteen detected metabolites, but the genus-level history is a reminder that bioactivity and toxicity often travel together in fungal chemistry and must be evaluated in parallel.

The choice of source organism is also part of the story. Almonds are a nutritionally celebrated food, and the fungi that colonize them occupy a niche that sits at the intersection of food safety and chemical innovation. Isolating a strain from a common pantry item and finding MIC values in the single-digit microgram range underscores how much pharmacological potential remains locked in ordinary environments. The Algerian team has previously described bioactive Penicillium strains from electronic waste and sea sand, and this new work extends that survey into the food chain, reinforcing the idea that productive fungi are distributed across wildly different habitats.

For now, the findings remain at the level of in vitro biochemistry: enzyme assays, microbial cultures, and cell lines, not patients. Translating a crude extract into a drug candidate typically requires years of fractionation, structural elucidation, mechanism-of-action studies, toxicity testing, and formulation work. But the comprehensive nature of this assessment, spanning antimicrobial, anti-inflammatory, antidiabetic, and antiproliferative activities alongside full chemical profiling and fermentation optimization, gives the almond fungus PB1 a unusually complete starting dossier. It is exactly the kind of well-characterized lead that natural-products researchers hope will seed the next generation of microbe-derived medicines, and it arrived, fittingly, from a handful of almonds.

Subject of Research: Bioactive secondary metabolites from an almond-derived Penicillium citrinum strain

Article Title: Unveiling the pharmacological potential of Penicillium citrinum PB1 isolated from almonds: a comprehensive bioactivity assessment

Article References: Unveiling the pharmacological potential of Penicillium citrinum PB1 isolated from almonds: a comprehensive bioactivity assessment. (n.d.). https://doi.org/10.1007/s13205-026-05066-6

Image Credits: AI Generated

DOI: 10.1007/s13205-026-05066-6

Keywords: Penicillium citrinum, almonds, secondary metabolites, antimicrobial activity, MIC, anti-inflammatory, antidiabetic, alpha-glucosidase, GC-MS, HPLC, fermentation optimization, natural products