Plant Research Reaches a New High

BY ADAM MOSES

Weizmann Institute scientists have revealed a groundbreaking production process for cannabinoids in a South African plant.

The ‘woolly umbrella’, or Helichrysum umbraculigerum, is unrelated to the cannabis plant but makes compounds found in cannabis that may have new medical uses. In a study published in Nature Plants, Weizmann Institute of researchers identified over 40 cannabinoids.

The cannabis plant makes over 100 different cannabinoids. But the woolly umbrella, a fast-growing perennial plant, is a respectable runner-up.

“We have found a major new source of cannabinoids and developed tools for their sustained production, which can help explore their enormous therapeutic potential,” commented Dr. Shirley Berman, who led the study in Prof. Asaph Aharoni’s lab at Weizmann’s Plant and Environmental Sciences Department.

Cannabinoids relieve pain, nausea, anxiety and epileptic seizures. Molecular receptors that respond to these compounds are common in humans suggesting cannabinoids that bind to them might be used to treat cancer to neurodegenerative diseases.

The woolly umbrella belongs to a different family of plants from cannabis. Relatives include sunflowers, daisies and lettuce. German scientists studied the plant over 40 years ago and found evidence it contains cannabinoids. Modern studies failed to reproduce their findings.

Now Berman and colleagues, using stateof-the-art technologies, confirmed that early report.

They used advanced analytical chemistry, including high-resolution mass spectroscopy, to identify cannabinoids it contains. Using nuclear magnetic resonance, researchers revealed the structure of over a dozen cannabinoids and related metabolites. They traced the biochemical pathway in the production of cannabinoids and determined where in the plant they are made.

The woolly umbrella manufactures cannabinoids primarily in its leaves, possibly giving it an economic advantage over cannabis, which makes compounds in the shorter-lived and harder-to-harvest flower clusters, or inflorescences.

Scientists found similarities between the woolly umbrella and cannabis. In particular, enzymes used in the cannabinoid production belong to the same families, throughout the first half of the biochemical pathway.

Six found in the woolly umbrella are identical to those in cannabis. The six do not include the two most famous ones, THC and CBD, but they do include cannabigerol, or CBG, a rising star of cannabinoid research.

It has potential therapeutic applications but lacks mood-altering effects. The acid form of CBG serves as a precursor for the production of classical cannabinoids supporting the idea the woolly umbrella could become a valuable source of plant-based cannabinoids.

“The fact that in the course of evolution two genetically unrelated plants independently developed the ability to make cannabinoids suggests that these compounds perform important ecological functions,” Aharoni noted. “More research is needed to determine what these functions are.”

His team are generating the newly discovered cannabinoid-making enzymes in tobacco plants.

Researchers used these enzymes to create finished cannabinoids in yeast, pointing to a new way of manufacturing compounds for research and the biotech industry.

The study’s findings might lead to engineering cannabinoids that don’t exist in nature. These could be designed to better bind to the human forms of the cannabinoid receptors.

The cannabinoids in the woolly umbrella might open new possibilities.

Berman noted: “The next exciting step would be to determine the properties of the more than 30 new cannabinoids we’ve discovered, and then to see what therapeutic uses they might have.”

Berman led the study with postdoctoral fellows Dr Luis Alejandro de Haro, Dr Adam Jozwiak and Dr Prashant D. Sonawane.

Prof Aharoni’s research is supported by the Laura Gurwin Flug Family Fund and Wolfson Family Charitable Trust & Wolfson Foundation. He is incumbent of the Peter J. Cohn Professorial Chair.