Home » Spider bite leads to new active ingredients – scinexx

Spider bite leads to new active ingredients – scinexx

A spider’s bite caused severe inflammation and cost the forearm of an Australian. But this tragic course of infection led an international team of researchers to new active substances, the so-called necroximes. The substances are formed by bacteria that live inside fungi. Scientists isolated her from the patient’s infected forearm tissue. The highly effective cell toxins can provide clues for the development of new cancer drugs. The researchers published their results in the journal Angewandte Chemie.

Numerous wild animals in Australia are particularly poisonous, including many spiders. A team led by Christian Hertweck from the Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute – (Leibniz-HKI) in Jena, together with Australian colleagues, got to the bottom of an unusual case: In the 1980s, a spider bit one Australian finger. A mixed infection developed in the forearm, which doctors could only stop by amputation. At that time, research colleagues isolated the fungus Rhizopus microsporus from the dead – necrotic – tissue. Hertweck and his colleagues discovered that bacteria in turn live inside the cell of this fungus. According to the analysis by the Jena researchers, they are the ones who produce an entire poison cocktail. Part of this mixture, the so-called rhizoxins, was discovered at Leibniz-HKI a few years ago. Now new molecules with a completely different structure have been added, which are called necroximes. They belong to the substance class of benzolactone enamides. Even the smallest amounts of these necroximes cause human cells to die.

The team also examined how the bacteria make these unusual connections. To do this, the researchers analyzed the genome of the bacteria. Using bioinformatic analyzes, they decoded a large number of biosynthetic genes. They encode a kind of molecular assembly line on which the necroximes are formed. Small molecular building blocks are assembled and modified using a biochemical program. Each individual domain of the enzymatic assembly line is responsible for a special reaction step until the finished molecule is finally released. Since necroximes and related substances have a toxic effect on human cells, they can be used as medicines for cancer. However, chemists often have to adjust the molecular structure to improve the pharmacological properties and to minimize undesirable effects. The enzymes of biosynthesis are a suitable tool provided by nature for the scientists. By decoding the responsible genes, natural product researchers are now able to specifically reprogram the biosynthesis of active ingredients. They also found similar genetic codes in the genomes of numerous other bacteria, which they identified as drug producers.

For Christian Hertweck, who also holds a chair at the Friedrich Schiller University in Jena, natural partnerships are a source of scientific inspiration: “The complex coexistence of different organisms – here bacteria, fungus and spider – is largely controlled by chemical substances. With the Necroximen, we have discovered new toxic natural substances that could possibly also be useful for humans. ”The Jena researchers are pursuing this approach in their own research area. Hertweck and many colleagues in the Collaborative Research Center ChemBioSys are dedicated to chemical language in organism communities. In the Cluster of Excellence Balance of the Microverse, the scientists are also investigating the molecular interplay of microorganisms with other organisms and the environment. Such findings are of medical interest, but can also help to understand and influence environmental processes. (Angewandte Chemie International Edition, 2020; doi: 10.1002 / anie.201916007)

Source: Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute (HKI)

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