In an article recently published by the journal Scientific ReportsIranian researchers and a team from Laval University announce that they have discovered a species of microscopic fungus that produces morphine and codeine. This fungus would be part of the microbiota of a species of poppy, the bract poppy, which grows naturally in Türkiye and Iran.
“More and more research shows that plants contain fungi or bacteria, called endophytes, with which they live in symbiosis. These endophytes are in a way the microbiota of plants,” explains one of the authors of the study, Roger Levesque, professor at the Faculty of Medicine and researcher at the Institute of Integrative and Systems Biology (IBIS) of the Laval University.
For a long time, scientists believed that fungi that lived in plants were latent pathogenic organisms. In the last quarter of a century, studies have instead shown that endophytes and their host maintain relationships that are beneficial to both parties. “The host plant protects the fungus and provides it with essential elements for its survival. For its part, the fungus produces molecules which promote the growth of the plant, which increase its resilience to stress or which participate in its defense against pathogens or insects,” summarizes Professor Levesque.
Three IBIS members joined forces with Iranian researchers to study the endophytes of four poppy species that live in the wild in Iran. Remember that the poppy family includes species that produce alkaloids such as morphine, codeine, papaverine and thebaine, which are used medicinally.
Their work made it possible to isolate six strains of fungi which produce morphine and other opiates such as codeine. This is the first study to report the production of such molecules by endophytes.
The mushroom Pithoascus kurdistanesis photographed under a microscope at two stages of its life cycle.
-One of these fungi, isolated from the bract poppy, is a new species named Pithoascus kurdistanesis. The poppy produces thebaine, but it does not produce morphine or codeine. “Endophytes have co-evolved with their host for hundreds of millions of years, which explains why they are not eliminated,” explains Professor Levesque. Natural selection may have favored endophytes that synthesize molecules similar to those that promote the growth and survival of their host. It is also possible that this similarity results from an exchange of genes between an endophyte and its host.
In order to establish whether it was possible to cultivate P. kurdistanesis In vitro, the research team placed this mushroom in a medium containing potato carbohydrates in solution. “The results were conclusive,” reports Roger Levesque. We obtained 23 mg of morphine and 3 mg of codeine per gram of mushroom produced. This is a performance that can be described as very good,” he believes.
The research team then sequenced the complete genome of P. kurdistanesis. “We have identified the genes in the fungus that are responsible for the production of morphine. The next step is to integrate these genes into bacteria that can be easily grown in bioreactors. We will then have a complete and efficient system which could be used for the production of morphine for medical purposes.”
— Roger Levesque
The first author of the study published in Scientific Reportsa journal of the Nature Research group, is the research professional Sima Mohammadi, member of Roger Levesque’s team. The other signatories are Roger Levesque, Antony Vincent, professor at the Faculty of Agricultural and Food Sciences at Laval University, and their Iranian colleagues Bahman Bahramnejad, Jafar Abdollahzadeh, Samaneh Bashiri, Mohammad Majdi and Jalal Soltani .
