A fungal chemistry in a flowering plant

In 1960 Albert Hofmann and Hans Tscherter, at Sandoz in Basel, analysed ololiuhqui, the seeds of Turbina corymbosa that Aztec healers had used in divination and that Richard Evans Schultes had identified botanically in 1941.^{[1, 2]} They found lysergic acid amide (ergine) and its isomer isolysergic acid amide as the main active alkaloids, with clavine alkaloids alongside.^{[2, 3]} The same family of compounds occurs in Ipomoea tricolor (also called I. violacea), the tlitliltzin of the Aztecs.^[4] Hofmann already knew these structures: they were the ergot alkaloids he had spent his career on, from which he had made LSD in 1938.

That was the surprise. Ergot alkaloids are made by fungi, chiefly the ergot fungi of grasses (Claviceps) and the grass endophytes (Epichloë).^{[5, 6]} Finding them in a dicotyledonous plant family with no obvious fungal infection suggested either that the plants had evolved the pathway independently, or that a fungus was hiding in plain sight.

The evidence that a fungus makes them

1. Fungicide removes the alkaloids (2004). Treating Ipomoea asarifolia with fungicides eliminated its ergoline alkaloids, but not its volatile oil, and the loss coincided with the disappearance of fungal hyphae on secretory glands on the upper leaf surface.^[7]
2. The fungus is identified (2006). Of 13 fungi isolated from I. asarifolia, only one, an epibiotic fungus on the leaf surface, belonged to the Clavicipitaceae, the ergot family. It could not be grown in culture and was transmitted through seed. It was the first ergot alkaloid producing clavicipitaceous fungus found on a dicot.^[8]
3. The genes are in the fungus, the alkaloids in the plant (2008). The gene for the first committed step of ergot alkaloid biosynthesis, dmaW, sits in a biosynthetic cluster in the fungus and was not detectable in the host plants. Yet the alkaloids accumulate almost entirely in the plant, not the fungus, which implies they are moved from fungus to host.^[9] Later work describes this transfer as running through the peltate glandular trichomes of the leaf.^[4]
4. A new genus (2011). Steiner and colleagues named the genus Periglandula (peri-, around; glandula, a small gland) for the fungi living on I. asarifolia and T. corymbosa. Their hyphae were never seen to penetrate the leaf, and no conidia, the asexual spores, were found.^[10]

Known species

The third species took 65 years to see. Ipomoea tricolor, the common garden morning glory, was known to contain ergot alkaloids, but no trace of a fungus had ever been found on it. In 2025 Hazel and Panaccione cultured the fungus from hyphae in emptied seed coats, sequenced its genome, and showed it was a distinct, spore-less Periglandula, which they named P. clandestina. It was most abundant in the seedling stem below the seed leaves and was absent from roots, even though the roots were rich in alkaloids.^[11]

What the alkaloids do for the plant

Seeds of symbiotic morning glories can hold ergot alkaloid concentrations up to a thousand times higher than endophyte-infected grasses.^[12] Seedlings move them selectively: in I. tricolor, lysergic acid amides were allocated to the roots while clavines stayed in the seed leaves.^[12]

A survey across the morning glory family found ergot alkaloids concentrated in four clades, each with its own alkaloid profile, more common in species with larger seeds, and rising with seed mass. The authors read this as a heritable symbiosis that spread by vertical transmission and host speciation, consistent with the defensive symbiosis hypothesis: the fungus's alkaloids protect seeds and seedlings from natural enemies.^[13] That hypothesis is well supported in grasses. In morning glories it fits the pattern, but direct tests are still few.

Three fungi, one chemistry

From fungus to pharmacology

All of these compounds share the ergoline ring system, and the lysergamides are amides of lysergic acid: ergine is the simple amide, ergometrine the amide with an amino alcohol, and LSD the diethylamide made in a laboratory. The LSD monograph follows the laboratory branch; the LSA profile covers the seed alkaloid itself.