biostudies-literatureUnknown16Jain A<h4>Introduction</h4>The endangered orchid <i>Dendrobium nobile</i> is the primary source of dendrobine, a neuroprotective sesquiterpene alkaloid, but unsustainable harvesting necessitates alternative production platforms, such as the endophytic fungus <i>Trichoderma longibrachiatum</i> MD33. However, the fungal dendrobine pathway and its regulatory mechanisms remain uncharacterized, limiting its biotechnological exploitation.<h4>Methods</h4>This study investigated cinnabar (HgS)-induced hormesis to elucidate the stress-mediated metabolic reprogramming of dendrobine biosynthesis through integrated transcriptomic and metabolomic profiling.<h4>Results</h4>Subtoxic HgS concentrations (1.0-4.0 μg/L) triggered ROS signaling, upregulating the mevalonate pathway, terpenoid synthases (TPS1/2), andFrontiers in microbiology1657982https://www.ebi.ac.uk/biostudies/studies/S-EPMC12634576biostudies-literatureCinnabar-induced hormesis in &lt;i&gt;Trichoderma longibrachiatum&lt;/i&gt; MD33: multi-omics elucidation of a fungal-specific dendrobine biosynthesis pathway.PMC12634576Jain ASarsaiya SGong QfalseCinnabar-induced hormesis in &lt;i&gt;Trichoderma longibrachiatum&lt;/i&gt; MD33: multi-omics elucidation of a fungal-specific dendrobine biosynthesis pathway.<h4>Introduction</h4>The endangered orchid <i>Dendrobium nobile</i> is the primary source of dendrobine, a neuroprotective sesquiterpene alkaloid, but unsustainable harvesting necessitates alternative production platforms, such as the endophytic fungus <i>Trichoderma longibrachiatum</i> MD33. However, the fungal dendrobine pathway and its regulatory mechanisms remain uncharacterized, limiting its biotechnological exploitation.<h4>Methods</h4>This study investigated cinnabar (HgS)-induced hormesis to elucidate the stress-mediated metabolic reprogramming of dendrobine biosynthesis through integrated transcriptomic and metabolomic profiling.<h4>Results</h4>Subtoxic HgS concentrations (1.0-4.0 μg/L) triggered ROS signaling, upregulating the mevalonate pathway, terpenoid synthases (TPS1/2), and2025-01-01T00:00:00Z20252026-05-19T03:23:09.854Z2026-05-19T03:12:00.481ZS-EPMC126345764127798010.3389/fmicb.2025.1657982