Thursday, July 02, 2026

  

The broader a fungus’s diet, the better it kills insects and helps plants



University of Maryland






UMD entomologists have discovered that a single underlying trait—metabolic breadth, or the range of nutrients a fungus can use—links its ability to kill insects, partner with plants and thrive in different ecological roles. Rather than trading one lifestyle for another, some fungi become better at all of them.

Many fungi lead triple lives—acting as deadly insect pathogens, decomposers in the soil and helpful partners living inside and transferring insect-derived nitrogen to plant roots. Scientists have long wondered what allows a single species to pull off these very different roles.

A new study offers a surprisingly simple answer: metabolic flexibility—the ability to use many different food sources. Working with the insect-killing fungus Metarhizium robertsii, University of Maryland entomologists found that strains capable of using a wider range of nutrients were both faster and deadlier at killing insects and more effective at colonizing plant roots. The findings were published July 1, 2026, in the Proceedings of the National Academy of Sciences.

"We expected to see a trade-off—that becoming a better plant partner would come at the cost of being a good killer or vice versa," said the study’s senior author Raymond St. Leger, a Distinguished University Professor of Entomology at UMD. "Instead, the two abilities rise and fall together, and what links them is the fungus's underlying nutritional flexibility." 

Different strains, different lives

The researchers combined genome-based analysis of eight M. robertsii strains spanning the species' evolutionary tree with laboratory tests measuring virulence, plant-root colonization, toxin activity and growth on 95 different nutrients. They chose to study M. robertsii because it’s already used worldwide as a natural biological control agent against insect pests and is increasingly being explored for its ability to promote crop growth. 

St. Leger and entomology postdoctoral associate Huiyu Sheng (Ph.D. ’24, entomology) found that the strains split into two distinct groups. The fungal strains that diverged early (at least 6 million years ago) behaved like “sleepers.” They kill insects slowly but pour resources into multiplying inside the host and producing huge numbers of spores, allowing them to survive until they encounter another host. Fungal strains that diverged more recently behave like "creepers." They germinate quickly on both insect skin and plant roots, kill rapidly, often deploy paralyzing toxins and grow as creeping threads from insect cadavers onto nearby roots, rather than forming spores.

The key difference between these two fungal strategies was metabolic breadth—the range of nutrients each strain could feed on. Fungi that could grow on a wider menu of sugars, amino acids and organic acids consistently proved better at both infecting insects and colonizing plant roots.

New thinking, new applications

The new study’s results reframe some insect-killing fungi as broadly "environmentally competent" organisms—whose ability to attack insects and partner with plants comes from the same nutritional toolkit. The team’s findings provide a useful model for understanding how microbes evolve the capacity to switch ecological roles.

"Instead of forcing fungi to choose between being insect killers or plant partners, evolution appears to have favored strains that are simply better at making use of whatever resources they encounter," St. Leger said. "Their versatility begins with metabolism."

The research also has practical implications for agriculture and could help researchers select fungal strains tailored for different agricultural goals. Broadly metabolizing strains of fungi could provide rapid suppression of insect pests while colonizing crop roots and promoting plant growth in the field. In contrast, fungal strains that produce large numbers of spores may be better suited for longer-term pest control.

“What we’ve learned could help growers use fungal pathogens more effectively,” St. Leger said.

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The paper, "Metabolic breadth links insect pathogenicity and plant association in Metarhizium robertsii," by Huiyu Sheng and Raymond J. St. Leger, was published in Proceedings of the National Academy of Sciences on July 1, 2026.

Research reported in this release was supported 100% by the U.S. Department of Agriculture’s National Institute of Food and Agriculture and Agricultural Research Service Biotechnology Risk Assessment Grants Program under grant number 2022-33522-38272 and the U.S. National Science Foundation’s Plant Biotic Interactions Program under grant number DEB-1911777. The content is solely the responsibility of the authors and does not necessarily reflect the official views of the USDA or the NSF.

About the College of Computer, Mathematical, and Natural Sciences

The College of Computer, Mathematical, and Natural Sciences at the University of Maryland educates more than 10,000 future scientific leaders in its undergraduate and graduate programs each year. The college's 10 departments and seven interdisciplinary research centers foster scientific discovery with annual sponsored research funding exceeding $250 million.

Unearthing new cancer treatments from fungi



Penn Engineers led by Xue ‘Sherry’ Gao have developed a gene-editing tool built specifically for fungi, unlocking a hidden library of molecules—including some with early anti-cancer promise—from one of biology’s most overlooked kingdoms.




University of Pennsylvania

Fungal sample 

image: 

Three fungal colonies in a single dish. Cultures like these yielded eight molecules new to science, three of them with early anti-cancer activity.

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Credit: Eric Sucar / University of Pennsylvania




Researchers have spent decades—and billions of dollars—sequencing animal and crop genomes, but fungi have historically been the forgotten middle child of genomics, only noticed when they’re ruining bread or colonizing toes.

“This neglect is kind of remarkable considering how fungi have shaped modern medicine,” says chemical and biomolecular engineer Xue “Sherry” Gao. “From the serendipitous discovery of penicillin to cholesterol-lowering statins, we owe many recent breakthroughs in longevity to fungal chemistry. But despite this, the vast majority of the fungal kingdom remains a black box.”

A main driver for this mystery is that when grown in sterile lab conditions, fungi turn off the drug-producing gene pathways they synthesize in the wild to fight off bacteria.

“To turn those silent pathways back on, we needed a powerful way to precisely manipulate fungal genome, such as editing their master regulatory genes, but traditional tools weren’t up to the task,” Gao says.

Now, Gao and her team at the School of Engineering and Applied Science have developed a novel genome editing tool, called fPE7max, to navigate the complex genetic architecture of thread-like molds known as filamentous fungi—think Aspergillus, or the Penicillium that gave the world penicillin—and finally unlock the secrets of this overlooked kingdom.

Their findings are published in Nature Biotechnology.

“We isolated 18 distinct complex molecules, eight of which possessed chemical structures entirely new to science,” says first author Chunxiao Sun, a postdoctoral researcher in the Gao Lab. “Of these uncovered molecules, three exhibited promising anti-cancer properties. These molecules can serve as lead compounds for disease treatment, providing a vital new pipeline for drug discovery.”

Sun says that one novel molecule showed selective toxicity against human breast, hepatic, and leukemia cancer cells.

Rewriting the genomics textbook for fungi

Over the last decade, CRISPR-Cas9 has been the headline-grabbing gene-splicing tool. But Gao explains that in filamentous fungi, which are rich sources of antibacterial compounds, it can be a blunt instrument, resulting in unintended mutations.

A newer technology called prime editing avoids double-strand breaks entirely, allowing for precise control over DNA sequences. But adapting prime editing for the fungal kingdom was a challenge.

First, the team had to ensure their genetic instructions actually survived the trip through the cell. Prime editing relies on a guide RNA—a molecular instruction manual that tells the tool where to go and what new code to write. But when researchers try to make massive edits, these instruction manuals can get unreasonably long, making them fragile and prone to degrading before the editing job is done.

Their workaround was integrating a special protein—fLa—into their tool. fLa acts as a sturdy, protective binder that shields the fragile RNA instructions, allowing fPE7max to handle the massive DNA insertions and deletions that cause other tools to break down.

Second, the team had to stop the fungal cells from spotting the researchers’ new edits, flagging them as errors, and reverting the DNA back to its original sequence. To outsmart that, the team incorporated a specialized protein that mutes the fungus’s natural repair system just long enough for the new genetic code to permanently take hold.

Ancient organisms, new science

The resulting platform, fPE7max, achieves editing efficiency approaching 90%. And by using fPE7max to flip the switch on these silent fungal gene clusters, the team uncovered previously unknown compounds.

To test their new tool, the researchers targeted the regulatory sequences of a master gene called laeA, which controls a vast network of biosynthetic pathways. By using fPE7max to precisely edit out the molecular roadblocks that naturally keep this gene’s translation repressed, they successfully awakened silent gene clusters across several different fungal species, finding molecules with promising anti-cancer properties.

“It’s a compelling proof-of-concept demonstrating that the next generation of life-saving therapeutics might already exist in nature,” Gao adds.

Looking ahead, the team plans to deploy fPE7max across a much wider array of fungal species to continue hunting for novel natural products. The researchers hope to move away from the treasure-hunt approach of searching for wild fungi that might produce useful drugs and into an era of systematic optimization.

Xue “Sherry” Gao is the Presidential Penn Compact Associate Professor in the Department of Chemical and Biomolecular Engineering, the Department of Bioengineering, and the Center for Precision Engineering for Health at the University of Pennsylvania.

Chunxiao Sun is a postdoctoral researcher in the Gao Lab at Penn Engineering.

Other authors include Chris Keum, Qiuyue Nie, Yihui Shen, and Naomi Straub of Penn Engineering.

This research was supported by the National Institutes of Health (NIH grant R35GM138207) and startup funds provided by the University of Pennsylvania.

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