Zombie fungus: how does this not so fun guy synthesise a cancer drug?

11 February 2020

Researchers are studying zombie fungus in efforts to reduce the price of an anti-cancer drug.

Cordycepin is a metabolite produced by members of the Cordyceps genus, more commonly known as ‘zombie fungus’. As well as being an important metabolite in the infection process, cordycepin has anti-cancer properties. Previously the process for biosynthesis of the compound was unknown, despite the increasing number of research studies on cordycepin for various health disorders. Ahmad Supamin, a postgraduate student at Shizuoka University in Japan, has been studying how the fungus species Cordyceps militaris can synthesise cordycepin.

Usually, oxygen is vital for fungal survival, however C. militaris are able to survive in the hypoxic, low oxygen environments of the insects they infect. Normally fungi respond to hypoxic conditions by activating genes that will help the fungus survive, but Ahmad found that C. militaris produces a higher amount of cordycepin in hypoxic conditions, suggesting that a lack of oxygen might induce cordycepin production.

Zombie fungus are famous for growing inside insects and taking over their bodies. By using cordycepin and other inhibiting agents, C. militaris can take over the insect, completely controlling its behaviour. Once the fungus has taken over the body of the insect and depleted it of its nutrients, it needs to continue its life cycle. The fungus grows a stem out of the insect’s body, which becomes the fruiting body and eventually releasing spores which will go on to infect more individuals.

Before now, the effect of cordycepin on insects was unreported, however it is now thought that the compound binds to the insect’s adenosine receptor. Adenosine is an important chemical found in many living systems and is important in many biochemical processes and the regulation of blood flow to organs.

Cordycepin has demonstrated multiple physiological functions that could help with cancer treatment, including preventing the spread, or metastasis of cancer. Unfortunately, cordycepin is expensive to produce. Ahmad hopes that this research will lead to the development of a more economically viable way of producing cordycepin for medicinal use, saying “hopefully the results of this study will contribute to overcoming those problems.”

It is evident that the hypoxic environment the fungus experiences in the insect is important for the production of cordycepin and now Ahmad says he is “trying to connect each piece of the puzzle” by looking at other metabolites produced by the fungus and use genome editing tools.

Ahmad Supamin will present his research as part of the Thriving under stress: manipulation of cellular responses by viruses session at the Microbiology Society’s Annual Conference in Edinburgh this year. His poster, titled ‘Intercorrelation Mechanism of Hypoxia and Cordycepin Biosynthesis in Zombie Fungus’ will be available to view on Thursday 2 April and Friday 3 April, with presentations taking place on Thursday evening between 18:30–20:00.