The fruiting bodies of bambusicolous Shiraia fungi have long been used in traditional Chinese folk medicine. Hypocrellin A (HA) is a bioactive perylenequinone from the fruiting bodies and serves as an efficient photodynamic therapy photosensitizer.

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Scientists have uncovered a molecular interplay between the host fungus Shiraia and its bacterial partners. When co-cultured without physical contact, bacterial volatile organic compounds (VOCs) of Rhodococcus sp. No. 3 – particularly dimethyl trisulfide and acetophenone – boosted fungal production of HA by 3.86-fold. 

The VOCs increased membrane permeability and reactive oxygen species (ROS) in fungal cells, activating key HA biosynthesis genes. Conversely, light-activated HA inhibited bacterial growth through ROS generation, triggering a surprising counter-response: Rhodococcus sp. No. 3 ramped up production of antioxidant carotenoids (β-carotene, astaxanthin, etc.) by 1.76-fold to shield itself. 

Feedback loop

“This VOC-induced HA stimulates bacterial carotenoid synthesis, creating a feedback loop,” explains the research team. The bacterial carotenoids demonstrated exceptional radical-scavenging capacity (67% hydroxyl radical neutralization), suggesting mutual adaptation within the fruiting body microenvironment. 

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Source: Jian Wen Wang, College of Pharmaceutical Sciences, Soochow University, Suzhou, China

A “donut” plate assay was established to assess the interactions between host Shiraia sp. S9 and the bacterial isolates from the fruiting body. Rhodococcus sp. No. 3 induced hypocrellin A (HA) biosynthesis in its fungal host through volatile-mediated elicitation, prompting Shiraia to leverage photoactivated extracellular HA for generating antibacterial reactive oxygen species that suppressed bacterial competitors. Rhodococcus countered this oxidative assault by synthesizing protective carotenoid antioxidants.Credit

The study, published in Mycology, reveals how cross-kingdom signaling regulates secondary metabolites in fungal microbiomes. This mechanism could enable dual-production of fungal HA for photodynamic cancer therapy and bacterial carotenoid antioxidants through co-culture biotechnology.