A toolbox for creating new drugs

ETH microbiologists led by Markus Künzler have discovered a remarkable enzyme in a fungus. They now want to use it to develop new drugs. 

Fungi appear to offer a truly inexhaustible reservoir of new substances. One such fungus is the jack-o'-lantern mushroom (Omphalotus olearius), which is found throughout the Mediterranean region and has a fruiting body that glows in the dark.

But it's not this special effect that has medical researchers interested; it's an enzyme recently discovered by ETH researchers led by the microbiologist Markus Künzler.

This enzyme, OphA, forms a key part of a metabolic pathway that keeps pests away from the jack-o'-lantern mushroom. "Fungi protect themselves from predators and competitors using a cocktail of toxins, many of which are proteins or peptides," says Künzler.

The jack-o'-lantern mushroom uses the OphA enzyme to provide the backbone of one of these peptides with additional methyl groups. Only upon this chemical alteration and subsequent cyclisation does the peptide, omphalotin A, function as a toxin. The mushroom uses it to ward off pests such as roundworms.

Fungal peptides also serve as drugs in medicine. One of the most well-known is cyclosporin A, which has been used in organ transplants, autoimmune diseases and cancer medicine for almost 40 years.

This peptide carries methyl groups on its backbone as omphalotin A. The ring shape and the methyl groups are responsible for cyclosporin A's advantageous pharmacological characteristics, in particular its oral availability – a factor which is at present a significant obstacle for peptide-based drugs.