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Berman et al., Sci. Adv. 12, eaeb3034 (2026) 1 April 2026

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P L A N T S C I E N C E S

Complete biosynthesis of psychedelic tryptamines from

three kingdoms in plants

Paula Berman1,2

*†, Janka Höfer 1

†, Herschel Mehlman1

, Efrat Almekias-Siegl1

, Olga Khersonsky 3

,

Younghui Dong 4

‡, Uwe Heinig4

, Liron Sulimani5

, Let Kho Hao1,2

, Shahar Cohen2

, Yoav Peleg4

,

Sagit Meir1

, Ilana Rogachev 1

, David Meiri5

, Sarel J. Fleishman3

, Asaph Aharoni1

*

Psychedelic indolethylamines with therapeutic potential are naturally produced in plants, fungi, and animals.

Here, we elucidated the complete N,N-dimethyltryptamine (DMT) biosynthetic pathway in hallucinogenic plant

species traditionally used in shamanic rituals for spiritual healing. Leveraging the similarities in their chemical

structures, we reconstructed in one plant assay the full biosynthetic pathways of five renowned natural psyche-

delics; psilocin and psilocybin found in mushrooms, DMT from plants, and bufotenin and 5-methoxy-DMT secret-

ed by the Sonoran Desert toad. We further engineered halogenated analogs of these molecules, which do not

naturally occur in plants and exhibit prospective therapeutic potential for psychiatric conditions. Blending cata-

lytic functions across the tree of life, coupled with metabolic engineering guided by rational protein design of

mutant enzymes, enabled substantially more efficient in planta production of the indolethylamine components.

This work establishes a versatile platform for concurrent biosynthesis and diversification of psychoactive indole-

thylamines, paving the way for their production in plants.

INTRODUCTION

For thousands of years, psychedelic substances have been used by

indigenous cultures as entheogens in rituals intended to induce al-

tered states of consciousness for spiritual and therapeutic purposes.

Psilocybin-containing mushrooms were central to ancient Aztec

ceremonies (1), while N,N-dimethyltryptamine (DMT), the pri-

mary psychoactive component of ayahuasca, has long been used

in traditional Amazonian rituals. This ceremonial brew combines

Psychotria viridis (a natural source of DMT) with Banisteriopsis caapi,

which provides β-carboline monoamine oxidase (MAO) inhibi-

tors that render DMT orally active (1, 2). Similarly, 5-methoxy-N,N-

dimethyltryptamine (5-MeO-DMT), found in the secretion of

the Sonoran Desert toad (Incilius alvarius) and in several plant spe-

cies, is thought to have been used ceremonially by indigenous

groups in northern Mexico (3). 5-MeO-DMT has been described

as the most potent DMT analog, being about 4- to 10-fold more po-

tent than DMT in humans and is known to induce psychedelic ex-

periences that are distinct from those of DMT (4). Knowledge of

the traditional use of these molecules has fueled contemporary

therapeutic interest in psychedelics as treatments for neuropsychiat-

ric conditions.

Recent studies have shown that classical indolethylamine psy-

chedelics promote neuroplasticity and modulate serotonergic cir-

cuits, primarily through 5-HT 2A receptor activation (5–7). These

compounds have demonstrated therapeutic potential for depression,

anxiety, posttraumatic stress disorder, and addiction (5–8), with psi-

locybin receiving Food and Drug Administration Breakthrough

Therapy designation for major depressive disorder in 2019 (6, 7).

Although widely considered hallucinogenic, psilocybin itself func-

tions as a prodrug, undergoing enzymatic dephosphorylation in the

digestive tract and liver to produce psilocin, the active compound

responsible for its psychoactive effects. DMT is produced by a broad

range of plant species and, in low abundance, by certain animals (2).

When administered via smoking or intravenous injection, it pro-

duces rapid and intense psychoactive effects that typically peak with-

in 5 min and subside within 30 min, due to rapid metabolism by

MAO enzymes in the liver. Coadministration with MAO inhibitors

can extend the half-life of DMT in vivo (2). The traditional use of

ayahuasca exemplifies how combining compounds from different

sources can enable oral activity; however, such combinations require

carefully balanced dosing to mitigate adverse effects associated with

MAO inhibition (9).

The expanding clinical interest in psychedelics as therapeutics

has sparked the need for scalable and versatile production platforms

and structural diversification (10, 11). Traditionally, the supply of

psychedelics relies on natural producers, mainly plants, fungi, and

the Sonoran Desert toad. Harvesting these organisms for their psy-

choactive compounds raises ecological and ethical concerns, being

increasingly threatened by habitat loss and overexploitation (12).

While synthetic routes for these compounds are available and, in

some cases, relatively straightforward, they still require compound-

specific reactants, can lead to unwanted intermediates and prod-

ucts, and require several processing steps (2, 13, 14). Biocatalys

My yard was infested with bur clover, horrible stuff when you have pets. Worse when your pets are poodle mixes. 

Other clover yeah they chill. 

You can play it on the original Xbox, there was a leak maybe 2020 of a prerelease / wip.

I should grab some screencaptures of the ingame, but I'm sure there are plenty out there.

My services are quite small (static website, forgejo and a couple more services) but see no performance issues.

Running 50 on one machine, four on my fileserver and another on a hacked up hp eliteone (no screen) which runs my 3d printer. Believe my immich container is a nspawn under nixos too. 

Some are a wip but the majority are in use. Mostly internal services with a couple internet facing, I've got a good backlog of work to do on some with some refactoring my nixos configs for many too 😅. 

From my Erying ES system: 

Not your traditional TVs but look and see if you can get some TVs aimed at venues / advertising. I can see an LG IPS display, 98 inch for sub 10k AUD including shipping (98UM5J-B). 

Phillips, LG, Samsung and others offer commercial panels without the rubbish that consumer panels are infected with these days. 

Yeah the LEDs were always handy to have, and the coloured notifications on the trackball (nexus 1) with a third party app was super cool at the time. My trackball after a few years got pretty dirty and didn't want to clean with chemicals in fear of damaging it. 

Currently using a Nothing (3) which is somewhat similar with the small led display on the back. 

Nexus one had the trackball, the hero had a sensor or did both? IDK it's been some years since I still had my nexus one. Maybe I'm thinking of the HTC Desire with the sensor. 

I do remember running the original version(s) of MIUI on my nexus one, ahh simpler times. 

“From the ID 2all onwards, we will have physical buttons for the five most important functions – the volume, the heating on each side of the car, the fans and the hazard light – below the screen,” 

Climate controls are one but sure, five most important functions. Honestly rip out the touch screen, implement buttons just as they had been previously then add the display; preferably with a decent HID as Mazda have done. 

I'm still driving a mk6 golf and really can't imagine not having easy access to those features. 

Ahh spotted another one! 

https://git.galing.org/kel/nixos

Mine is a mess but works for me ¯\_(ツ)_/¯ 

I'd dare say the easier method, from memory the p6 should have a charge limit in the stock firmware.

I've not an old Samsung s10+ kicking around with corrupted firmware, should really take a look at it and see if it can be up and running again. Not that I need more cores, ram, cameras or any additions to my equipment but just because.

It fassinates me that consumer hardware, and low power at that goes wasted so often. So many small form factor devices such as phones, with built in ups aren't being leveraged. But I guess that comes down to proprietary binary blobs and developer work on a per device basis.

I might have to investigate what platforms mobile nixos supports and see if it's cheap enough to dabble with.

Depends on network load, power is cheapish for me right now but much better than peak. During the day around 11am onwards energy is dirt cheap, and sometimes (rarely) dips into the negatives.

Provider offers wholesale rates plus a flat fee. There are some protections in place to shield consumers from massive bills when the rate jumps to $$/KWh