Fungus Becomes Factory For African Sleeping Sickness Drug

By genetically modifying a fungus, researchers in Japan can produce large quantities of ascofuranone, a promising antibiotic for the treatment of African sleeping sickness.

AsianScientist (Apr. 22, 2019) – Researchers in Japan have turned a fungus into a factory for producing a natural antibiotic that can be used to treat African sleeping sickness. They published their findings in the Proceedings of the National Academy of Sciences.

African trypanosomiasis, or African sleeping sickness, affects thousands of people in remote, rural areas of sub-Saharan Africa each year. People can develop the disease by being bitten by a fly which carries a parasite. The parasite then travels through the patients’ blood stream into the nerves of patients’ brains and spinal cords, resulting in death.

In the present study, researchers led by Professor Ikuro Abe from the University of Tokyo, Japan, sought to produce an antibiotic against the parasite that causes African sleeping sickness. Rather than synthesize the antibiotic chemically, the researchers relied on the fungus Acremonium egyptiacum, which naturally produces two different types of antibiotic. One is toxic to humans, but the other—ascofuranone—was identified as a potential treatment for African sleeping sickness in 1996.

Abe’s research team identified that the fungus’s two antibiotics are both made from the same precursor molecule. After the precursor is created, two separate groups of enzymes produce the two different antibiotics.

Researchers can leave the precursor molecule and the genes responsible for the desired antibiotic completely unchanged by simply deleting the genes responsible for the other toxic antibiotic.

“The gene cluster in the fungus is unique—by performing a simple genetic deletion, we have engineered a strain of the fungus that only produces high concentrations of the desired antibiotic,” explained Abe.

In every liter of fungus that researchers grow in the lab, the engineered strain of the fungus can produce 500 milligrams of antibiotic. The researchers have applied for a patent on the engineered strain of fungus. Collaborators at the Kikkoman Corporation, best known for making soy sauce, will pursue industrial-scale growth of the genetically engineered fungus and purification of the antibiotic.

The article can be found at: Araki et al. (2019) Complete Biosynthetic Pathways of Ascofuranone and Ascochlorin in Acremonium egyptiacum.


Source: University of Tokyo; Photo: Motomichi Matsuzaki.
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