The growth pattern of Cordyceps militaris on tulip silkworms. Shanghai Institute of Plant Ecology, Chinese Academy of Sciences
Cordyceps has more than 1500 species but not all of them fight cancer.
"If cordyceps found in the wild is detected as cordycepin, it must be contaminated."
On the morning of October 19, Wang Chengshu, a researcher at the Shanghai Institute of Plant Physiology and Ecology of the Chinese Academy of Sciences, told the surging news (www.thepaper.cn). In October, he just received the Asian Mycologist Award from the Asian Mycological Society.
Wang Chengshu has just received the "Asian Outstanding Mycologist Award" from the Asian Mycological Society. The Paper's reporter Wu Yuewei took a photo
At 9 p.m. on the 19th, he led the research team to publish a paper online in the international academic journal cell chemical biology, announcing that Cordyceps sinensis does not contain cordycepins, and saying that it is genetically determined.
"Because there is no cordycepin synthesis gene in Cordyceps sinensis, and there is no cicada flower," Wang Chengshu said.
The star molecule cordycepin has not completed clinical trials
For a long time, cordycepin has been a star molecule, repeatedly appearing in advertisements, and has also caused lawsuits and questions many times.
Cordycepin has long been claimed to have anti-cancer, antibacterial and other activities, but there has been a lack of sufficient clinical trial evidence. Up to now, the Food and Drug Administration has not approved cordycepin for marketing as a drug.
The history of cordycepin research dates back to 1950. In December of that year, German scientists published a paper in nature, and the first discovery of cordycepin was discovered. But for nearly 70 years, people didn't know how it was synthesized.
Cordyceps militaris The Paper reporter Wu Yuewei photographed
Cordyceps militaris contains cordycepin. Wang Chengshu's research group had an unexpected harvest when studying the synthesis path of cordycepin. They found an anti-cancer active ingredient called "pentastatin" in Cordyceps militaris. As early as 1991, "spironitatin" was marketed in the United States as an anti-leukemia drug approved by the US Food and Drug Administration (FDA). Its products are mainly produced by chemical synthesis.
Containing "spentastatin" means that Cordyceps militaris has certain anti-cancer properties. Unfortunately, Cordyceps sinensis and cicada flowers do not contain either cordycepin or "pentilstatin".
A variety of cordyceps, humans have found more than 1500 species. Courtesy of respondents
At present, humans have found more than 1,500 kinds of cordyceps, and Wang Chengshu's research group has carried out genomic research on 18 of them. They found that only Cordyceps militaris and Cordyceps Kyushu contained "pentilstatin" and cordycepin.
In addition, a mold nest aspergillus can also synthesize "pentastatin" and cordycepin. In the wild, Cordyceps sinensis may be contaminated with this mold, which contains trace amounts of cordycepin.
But you can't beat Cordyceps to death with a stick.
Wang Chengshu said they found more than two dozen gene clusters in the cordyceps genome that may synthesize the active substance, but as of now, their gene function is unknown.
7 years to discover the anti-cancer component "pentostatin" synthetic pathway
"Pentilstatin", an active anti-cancer ingredient, can be used as one of the molecular indicators to measure the quality standard of Cordyceps militaris.
Wang Chengshu said that whether the active ingredients and molecular indicators are clear is one of the challenges faced by Chinese herbal medicine when it enters the international market. In addition to the efficacy recorded in traditional Chinese herbal medicine texts, what other effects and new active ingredients there are, and the answer to this question is a gold mine.
Gene clusters in Cordyceps militaris synthesize both cordycepin (cor) and pentostatin (ptn). Shanghai Institute of Plant Ecology, Chinese Academy of Sciences
"Spentatin" and cordycepin always appear together. Further studies confirmed that "spentatin" is the umbrella of cordycepin. In the absence of "pentilstatin", cordycepin will be degraded.
Wang Chengshu revealed that as early as 2011, they sequenced the genome of Cordyceps militaris and published a related paper. But in order to figure out the synthesis route of cordycepin and the synthesis route of "spentatin", they spent nearly 7 years.
When this latest paper was published, one of the original doctoral students in the research group had graduated and was currently studying abroad.
The intake of cordycepin should not be excessive
Wang Chengshu said that from the treatment of malaria by Artemisia annua to the discovery of artemisinin; from Cordyceps militaris to the discovery of "spentatin", this is the internal strength that drug developers should cultivate.
Wang Chengshu said they have applied for patent protection for genes in the "spenstatin" and cordycepin synthesis pathways. In the future, these genes are expected to be applied to synthetic biology, using other bacteria or plants to synthesize "pentostatin" and cordycepin.
In addition, Wang Chengshu reminded that when people consume cordycepin daily, they should not overdose. The molecular structure of cordycepin is very similar to adenine nucleotides, and once phosphorylated cordycepin is incorporated during human DNA or RNA synthesis, it may cause genetic variation or loss of function. This is its anti-cancer mechanism, but it can also have a negative impact on the faster proliferating cells in the human body. In Cordyceps militaris, the researchers observed that the fungus degrades excess cordycepin.
Wang Chengshu speculated that "spentatin" and cordycepin are the "weapons" of Cordyceps militaris to adapt to the environment and can be used to fight other microorganisms in the wild environment.
The annual production of artificially cultivated Cordyceps militaris has reached more than 1000 tons. The picture shows Researcher Wang Chengshu observing Cordyceps militaris. Courtesy of respondents
They found that Cordyceps militaris had the highest amount of synthesis of "spentastatin" when it grew on silkworm pupae; when it was grown on rice, the amount of synthesis decreased; and when it was cultured in liquids, the amount of synthesis was minimal. The molecular mechanism is unclear. By culturing Cordyceps militaris on rice, the current annual production of Cordyceps militaris is about 1000 tons.
Cordyceps militaris growing on rice, photo by Wu Yuewei, a reporter of the surging news
Cordyceps is not mysterious, he said, but there are still many biological questions that are unclear. Insects are infected with fungi, and after getting fungal diseases, the remnants of their death, the fungal and insect complex, are cordyceps. In nature, in addition to Cordyceps militaris, there are also types of cordyceps such as spiders, ants, bees, locusts and so on. Of the more than 1,500 species of cordyceps that humans have discovered, in addition to the different types of insects, there are also differences in the types of infested fungi.
Cordyceps spiders Courtesy of the interviewee
Ant Cordyceps Photo courtesy of the interviewee
In addition to studying cordyceps, Wang Chengshu is also very interested in the fungus's control of insect behavior. Why do bat moth larvae have to crawl to two or three centimeters above the ground after being infected with fungi, and then grow cordyceps? Why do ants crawl to the top of a branch to die after being infected with fungi? He hopes to unlock more secrets about the wrestling between fungi and insects.