Destruxins are cyclic hexadepsipeptides, ring-shaped molecules assembled from amino acids and hydroxy acids, that more than forty known analogs call home. They are the chemical weapons that Metarhizium fungi deploy against insect hosts, disrupting immune cells and muscle function, and they also mediate the fungus’s interactions with plants. Beyond agriculture, destruxins have attracted attention in medical research for antiviral, antimicrobial, anticancer, antiangiogenic, and immunosuppressive properties. Yet the environmental triggers that switch their biosynthesis on or off have remained murky, with reports in the literature sometimes contradicting one another.

The research team, led by Pamela Vrabl at the University of Innsbruck’s Institute of Microbiology, hypothesized that light might act not as a simple trigger but as a modulator whose effects depend on the nutritional state of the culture. This idea rests on a growing body of evidence from other fungi, including Aspergillus nidulans and Penicillium species, where the same wavelength can either boost or suppress secondary metabolite production depending on the medium. To test this in Metarhizium, the team grew the production strain M. brunneum BIPESCO 5 in 4.5-liter stirred-tank bioreactors under two radically different diets: a nutrient-rich Sabouraud medium with 4 percent glucose, and a defined minimal medium in which nitrogen was the limiting nutrient.

Each medium was subjected to five illumination regimes: complete darkness, red light centered at 660 nanometers, green light at 528 nanometers, and blue light at 455 nanometers, all delivered at an intensity of 1.4 milliwatts per square centimeter, plus ultraviolet-A irradiation at 340 and 375 nanometers at 1.1 milliwatts per square centimeter. LED panels were mounted in front of the glass bioreactor vessels and shrouded in light-tight fabric to prevent cross-contamination between treatments. Irradiance was verified with calibrated photodiode power sensors and spectrometers, ensuring that differences in output could not be attributed to sloppy light measurement.

Across 21 independent bioreactor batch cultivations, each run for 90 hours with triplicate sampling at ten time points, the fungus followed the classic growth pattern of filamentous fungi under carbon excess: a lag phase, exponential growth terminated by depletion of the first essential nutrient, a prolonged deceleration phase, and finally stationary phase. In the nutrient-rich medium, phosphate ran out first; in the minimal medium, ammonium did. Destruxin production began only after exponential growth had ended, consistent with the general principle that secondary metabolites accumulate once primary growth stalls.

The first major result concerned nutrition alone. Cultures grown under nitrogen limitation produced roughly twice as much destruxin A and B in absolute terms as those in the rich medium—up to 42.9 milligrams per liter of destruxin A and 22.7 milligrams per liter of destruxin B in darkness, compared with 19.1 and 8.6 milligrams per liter respectively in the rich medium. When normalized to fungal dry mass, the gap widened dramatically: nitrogen-limited cultures produced up to five times more destruxin A and nearly seven times more destruxin B per gram of biomass than their well-fed counterparts. This aligns with the long-standing observation that reduced nitrogen availability tends to elevate secondary metabolite levels in fungi, although the authors note that the regulatory role of nitrogen in destruxin biosynthesis remains incompletely understood and that published reports on the topic vary considerably.

The second and more striking result was that light did matter—but its direction flipped with the diet. In the nutrient-rich medium, shorter wavelengths enhanced production: cultures exposed to ultraviolet-A, blue, or green light produced significantly more destruxin A than those kept in darkness or under red light, and biomass-normalized destruxin B also rose significantly with shorter wavelengths. In the nitrogen-limited medium, the same short-wavelength treatments had the opposite effect, significantly reducing destruxin A and B levels relative to darkness and red light. Red light, by contrast, behaved much like darkness in both media. Destruxin E, the third analog measured, showed no significant light response in either medium, though its concentrations fluctuated wildly between replicate cultures—possibly because the molecule hydrolyzes into a related form called destruxin E-diol.

Perhaps the most telling detail lay in the ratios. Although light exposure swung the absolute concentrations of destruxins A and B up and down, the ratio between the two remained essentially constant within each medium—roughly 70:30 in the rich medium and 60:40 under nitrogen limitation—regardless of wavelength. Statistical analysis confirmed strong positive correlations between the two metabolites across all light treatments, with Pearson correlation coefficients reaching 0.94 in the minimal medium and 0.97 when data from both media were pooled. This pattern suggests that the biosynthetic pathway for destruxins A and B, whose genes are known to be clustered in the Metarhizium genome, is governed primarily by nutritional status, while light modulates the total flux running through it rather than rerouting it toward one product or the other.

The findings place destruxin regulation alongside a broader phenomenon in fungal physiology: nutrient-dependent light responses, in which the same photic signal produces different metabolic outcomes depending on carbon and nitrogen availability. Similar crosstalk has been documented for sterigmatocystin production in Aspergillus nidulans, where changing the carbon source could reverse whether light or darkness favored toxin synthesis, and for the antibiotic xanthoepocin in Penicillium ochrochloron. For Metarhizium, whose ecological repertoire spans insect pathogen, soil saprotroph, and plant-associated endophyte, such flexibility makes evolutionary sense: the fungus encounters everything from absolute darkness underground to green-light-dominated leaf surfaces and full sun, and its chemistry presumably adapts accordingly.

For biotechnologists, the practical implications are immediate. Destruxin yields in fermentation could potentially be increased by co-optimizing nutrient formulation and illumination regime rather than treating light as an afterthought, and shifting the product profile toward a preferred analog might become feasible by tuning the two variables in concert. The authors caution that mechanistic and scale-up studies will be needed before such strategies reach the production floor, and they emphasize that rigorous standardization of both cultivation and light conditions—wavelength and intensity alike—will be essential for untangling the molecular machinery underneath. What the study establishes beyond doubt is that destruxin biosynthesis is not a simple on/off switch but a finely tuned adaptive system, one that listens to both the menu and the light before deciding what to make.

Subject of Research: Nutrient-dependent effects of light wavelength on destruxin biosynthesis in the entomopathogenic fungus Metarhizium brunneum

Article Title: Nutrient-dependent influence of red, green, blue, and UV-A light on the production of destruxin A, B, and E in Metarhizium brunneum bioreactor batch cultures

Article References: Schobert, J., Erckert, S. A., Schinagl, C. W., Schöbel, H., Strasser, H., & Vrabl, P. (2026). Nutrient-dependent influence of red, green, blue, and UV-A light on the production of destruxin A, B, and E in Metarhizium brunneum bioreactor batch cultures. Frontiers in Photobiology, 4, Article 1753405. https://doi.org/10.3389/fphbi.2026.1753405

Image Credits: AI Generated

DOI: 10.3389/fphbi.2026.1753405

Keywords: Metarhizium brunneum, destruxins, fungal photobiology, secondary metabolism, bioreactor cultivation, nitrogen limitation, light wavelength, entomopathogenic fungi, biological pest control, UV-A irradiation, biotechnology, fungal physiology