Mass Spec Roundup: Iridoids, Isoforms, and Carbon Currents

Full Circle: Long-Sought Enzyme Found in Iridoid Production

In a study published in Nature Plants, researchers at the Max Planck Institute for Chemical Ecology have identified the long-sought cyclase enzyme that catalyzes the final step in iridoid biosynthesis – the cyclization of precursors into nepetalactol, the core scaffold shared by all iridoids.

Led by Sarah O’Connor, the team combined single-cell transcriptomics, functional expression assays, and mass spectrometry–based metabolite analysis to pinpoint and confirm the enzyme’s role. By leveraging a new single-cell expression dataset from Carapichea ipecacuanha (ipecac), provided by Robin Buell’s group at the University of Georgia, the team could narrow hundreds of genetic candidates to a select few. Expression of these candidates in plants and bacteria revealed that one gene consistently produced nepetalactol, a result confirmed through LC–MS analysis of the reaction products.

“To our surprise, the enzyme we found belongs to a completely unexpected class – one known for catalyzing entirely different reactions,” said Maite Colinas, first author of the study. “We were able to show that this enzyme catalyzes the reaction we investigated and that the expected substance, nepetalactol, is formed.”

The discovery completes the iridoid biosynthetic pathway after decades of research, confirming that cyclization is enzymatically driven rather than spontaneous. The team now aims to investigate how this novel enzymatic function evolved and the detailed mechanism of cyclization – questions that could illuminate new principles of enzyme evolution.

Stress-Induced Changes in Brain Glycosylation Linked to Depression

Chronic stress alters sugar chemistry in the brain’s emotion centers, triggering depression-like behaviors, according to new research from the Institute for Basic Science (IBS).

Using high-resolution mass spectrometry to map O-glycan patterns across nine mouse brain regions, researchers found that stress sharply reduced sialylation – a sugar modification that stabilizes proteins – in the prefrontal cortex. The change was linked to decreased activity of St3gal1, a key glycosyltransferase enzyme, and to downstream disruptions in synaptic proteins that regulate inhibitory neurons.

Suppressing St3gal1 in healthy mice was enough to induce depressive behaviors, while boosting its expression reversed symptoms in stressed animals. The team concluded that these sugar-chain changes destabilize synaptic structures such as neurexin 2, weakening neural circuits that maintain emotional balance.

“This study demonstrates that abnormal glycosylation in the brain is directly connected to the onset of depression,” said research fellow Boyoung Lee. “It provides an important foothold for identifying new diagnostic markers and therapeutic targets beyond neurotransmitters.”

“Depression imposes a major social burden, yet current treatments remain limited,” added Director C. Justin Lee. “This achievement could extend not only to depression therapy but also to other mental illnesses such as PTSD and schizophrenia, paving the way for broader therapeutic strategies.”

Mapping Carbon Currents Along the Yangtze

A high-resolution molecular survey has revealed how dissolved organic matter (DOM) evolves along the upper Yangtze River – from glacial headwaters to the Three Gorges – shedding light on how Asia’s longest river shapes the global carbon cycle.

The team from Peking University analyzed DOM across a 3,500-kilometer transect using ultra-high-resolution Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS), fluorescence spectroscopy, and lignin phenol markers. The findings, published in Carbon Research, capture a striking molecular transformation driven by glaciers, grasslands, fire, and sunlight.

At the river’s source on the Tibetan Plateau, DOM was rich in nitrogen- and sulfur-containing molecules and labile carbohydrates – signatures of glacial melt and grassland input. As the river flowed eastward, wildfire-derived aromatic compounds appeared midstream before degrading under sunlight. Downstream, lignin-like, recalcitrant molecules accumulated from forested and agricultural runoff, peaking near the Three Gorges Dam.

“This challenges the old assumption that river DOM is mostly tree-derived,” said corresponding author Dongqiang Zhu. “In the headwaters, it’s the grasslands that feed the river’s carbon load.”

Next, the researchers plan to extend their molecular mapping to seasonal and vertical variations in the Yangtze system and to compare DOM transformations in other major Asian rivers, aiming to refine global carbon transport models.

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