Exploring how innovative approaches to fungal research are revealing nature's chemical secrets
Cichewicz's lab maintains one of the largest academic collections of fungal isolates in the world—approximately 88,000 specimens from diverse ecosystems across the United States 2 .
Beneath the forest floor, in the soil of our backyards, and even within the confines of a cereal-filled plastic bag, a silent chemical warfare has been raging for millions of years. Fungi, some of Earth's most ancient organisms, continuously engage in biochemical combat, producing sophisticated molecular weapons to attack competitors, defend territory, and survive in hostile environments.
These chemical innovations represent one of nature's most largely untapped pharmacopeias—a fact that natural products chemist Robert Cichewicz has built his career upon. Through unconventional methods and relentless curiosity, Cichewicz and his team are revealing nature's hidden chemical treasures, discovering compounds with potential to combat drug-resistant infections, neutralize parasites, and even solve the age-old problem of skunk odor 2 9 .
Robert Cichewicz's journey to becoming a leading natural products chemist was anything but conventional. He admits, "It pains me to admit it, but as a college student, I found chemistry classes boring—full of rote memorization about reactions and reagents that seemed to have little applicability to his life" 9 .
His initial academic passion was anthropology, where he investigated the role of chili peppers in Mesoamerican culture, history, and medicine. This research sparked his fascination with plants and their chemical properties, eventually leading him to ask deeper questions about the specific compounds responsible for biological effects 9 .
When establishing his own lab, Cichewicz made a conscious decision to pursue underexplored territories in natural products chemistry. "At the time, it was not to do what others were doing," he explains. "It's still a central tenet of what we do: we look for where there are gaps in what the natural products community is looking at" 9 .
In the early 2000s, this gap appeared to be fungi, which he describes as "the wild west of natural products, where there was a lot more unknown territory" 9 .
This vision led to the creation of the Natural Products Discovery Group (NPDG) at the University of Oklahoma, which has since assembled one of the largest academic collections of fungal isolates in the world—approximately 88,000 fungal isolates derived from every major biome in the United States 2 . Each fungus is used to create extracts enriched for natural products, enabling rapid testing for applications in human health, agriculture, and novel biomaterials.
For years, natural products chemists faced a persistent challenge: convincing fungi to produce their full gamut of metabolites under laboratory conditions. Standard protocols using Erlenmeyer flasks filled with broth tended to yield the same common mycotoxins repeatedly, limiting discovery of novel compounds 7 .
In 2007, Cichewicz began searching for alternative growth media by exploring Walmart aisles and his kitchen cabinets. The breakthrough came unexpectedly with a box of stale Cheerios. "Pretty soon we were getting rich, luxuriant lawns on top of the Cheerios," Cichewicz recalls. "The fungi grew in all the crevices, leaving behind fuzzy doughnut shells where the Cheerio used to be" 7 .
Fungi growing on unconventional media can produce unique metabolites not observed in standard laboratory conditions.
| Compound Name | Source | Biological Activity | Potential Applications |
|---|---|---|---|
| Bionectriols | Bionectria ochroleuca grown on Cheerios | Prevents biofilm formation of Candida albicans, enhances amphotericin B | Treatment of fungal infections |
| Pericosine A | Fungus from Alaskan soil sample | Neutralizes thiol compounds | Skunk odor neutralization, antifungal properties |
| Persephacin | Fungus from campus plant | Broad-spectrum antifungal activity | Treatment of drug-resistant fungal eye infections |
| Xanthoquinodins | Fungal isolates | Broad-spectrum anti-infective activity | Treatment of malaria, antibacterial applications |
One of Cichewicz's most fascinating discoveries began with cancer drug discovery but took an unexpected turn. Through a citizen science project that collected soil samples from across the country, his team discovered a fungus producing a molecule with an unusual structure—a hybrid containing a shikimate (typically found in plants) connected to a polyketide (typically produced by microbes) in a previously unseen configuration 4 .
As they investigated this compound, named pericosine A, they discovered its remarkable ability to attack and neutralize various antifungal compounds and toxins. This led them to brainstorm potential applications for this neutralizing capability, eventually considering whether it might effectively neutralize thiols—the organosulfur compounds responsible for skunk spray's potent odor 4 .
Pericosine A converts skunk thiols into odorless compounds at concentrations undetectable to the human nose.
| Method | Mechanism | Effectiveness | Drawbacks |
|---|---|---|---|
| Tomato juice | Masking odor | Temporary | Messy, doesn't eliminate odor, stains surfaces |
| Baking soda/hydrogen peroxide | Oxidation | Moderate | Skin irritation, bleaching effect |
| Commercial products | Variable | Mostly ineffective | Unknown ingredients |
| Chloramine-T solutions | Chemical neutralization | Effective | Skin and eye irritation |
| Pericosine A | Chemical conversion | Highly effective | Currently not commercially available |
One of the largest academic collections of fungal isolates in the world (88,000 specimens), sourced from diverse biomes across the United States 2 .
An unconventional but highly effective growth medium for fungi that encourages production of diverse secondary metabolites 7 .
Advanced analytical technology used to separate, identify, and quantify complex mixtures of fungal metabolites 5 .
Molecular biology techniques used to identify fungal species and classify them into genetic clades 5 .
Cichewicz's research approach extends beyond traditional academic boundaries through innovative citizen science initiatives. His team's soil collection project began as a way to expand their fungi library but "went viral in 2012," generating several thousand participation requests 9 .
The citizen science work evolved into an exhibit at Science Museum Oklahoma, featuring fungal videos, artwork, displays, and educational panels. Cichewicz highlights the impact of this outreach: "As a scientist, you're lucky if you can get 14 people to read your paper, but we've had a quarter-million or more people look at that exhibit" 9 .
Thousands of participants contributing soil samples from diverse environments across the country.
As natural products research evolves, Cichewicz's team remains at the forefront of methodological innovations. They have developed tools combining genetic barcoding and metabolomics to build natural product libraries with predetermined levels of chemical coverage 5 .
Looking forward, Cichewicz recognizes the potential of emerging technologies like artificial intelligence (AI) to transform natural products discovery. AI approaches can help identify patterns in complex chemical data, predict biological activities of unknown compounds, and optimize cultivation conditions 8 .
Identifying fungal metabolites effective against malaria and trichomoniasis
Targeting Gram-negative pathogens and antibiotic-resistant Mycoplasma
Understanding natural functions of fungal metabolites in ecosystems
Developing fungal solutions for environmental cleanup
Robert Cichewicz's career demonstrates the profound impact of curiosity-driven research and willingness to explore unconventional paths. From humble beginnings as an anthropology student fascinated with chili peppers to leading one of the most innovative natural products research programs in the world, his journey exemplifies how scientific passion can yield both fundamental insights and practical applications.
"When we look down the road, if everything works out as you expect, what's the product of this going to look like? Can we envision something larger than normal? Something exciting?... You better at least have a dream, because if you aren't dreaming at the beginning, then you're certainly going to be asleep by the end" 9 .
As we face growing challenges from drug-resistant infections, parasitic diseases, and environmental contamination, the chemical weapons that fungi have evolved over millions of years may offer solutions. Through the work of researchers like Cichewicz—who combine scientific rigor with imaginative approaches—we continue to uncover nature's hidden treasures, reminding us that sometimes the most profound discoveries can come from the most unexpected places: a stale cereal box, a roadside soil sample, or the curious mind of a researcher willing to ask "what if?"