10.10.2022 - Fungi: New mechanism for production of active substances discovered

Fungi produce thousands of active ingredients and bioactive substances, such as antibiotics or cytotoxins. Researchers are feverishly trying to decipher how this works in detail, because this knowledge can be groundbreaking for the development of pharmaceuticals or for improving food safety. A large international cooperation of the BOKU Institute of Microbial Genetics at the DAGZ in Tulln has now discovered a new mechanism that controls the production of bioactive substances.

Many active substances that fungi produce for different reasons have been used by humans. A famous example is penicillin - an active substance that fungi produce to fight off bacteria. "However, we do not yet know exactly when, for what reasons and how fungi produce these bioactive substances," explains Joseph Strauss from the Institute of Microbial Genetics (IMiG) at BOKU Vienna.

It costs fungi a lot of energy to produce bioactive substances. A sophisticated genetic regulation system therefore ensures that they are only produced when the fungus really needs them. If, for example, a starvation signal occurs because the fungus falls on a surface where it cannot utilise much, it reacts by producing defensive substances, since it is obvious that there are many competitors in the environment. Understanding how fungi translate environmental signals, such as the lack of nutrients, into the correct genetic circuits in the cell and start producing defence substances, for example, has been a research focus at the BOKU Institute of Microbial Genetics for many years. Strauss and his team, together with international research partners, have now discovered a new mechanism that controls this production.

The path between membrane and nucleus was a black box

"We already knew a lot about what happens on the outside of the membrane and also about what happens in the cell nucleus, but the signalling pathway in between was unclear," Strauss explains. Four protein partners, the so-called KERS chromatin complex (KdmB-EcoA-RpdA-SntB chromatin complex), are essential for signal transmission from the membrane to the nucleus. "Until now, this pathway has been like a black box," says Strauss, "a black box that we've been able to open and now better understand how this signalling cascade works." The team was able to prove that the fungal cell uses the proteins that actually control the large-scale structure of chromosomes very specifically to target and activate biosynthesis genes that are needed for the bioactive substances. "In addition, these so-called "chromatin regulators" also control different developmental stages of fungi, which in turn influences their ecology and spread as pathogens," explains Strauss. These new findings therefore help to better understand the function of these molecules in nature, as well as to improve the production of biopharmaceuticals. Even our food and feed are affected, because contamination with toxins is based on the same principles of gene regulation. In addition, the results will feed directly into the ongoing screening programmes of the BiMM research platform (www.bimm-research.at), which aims to find new bioactive compounds for medicinal and agro-forestry applications.

The study was published in the journal Nucleic Acids Research:
​​​​​​​pubmed.ncbi.nlm.nih.gov/36095118/

Contact:
Joseph Strauss, Univ.Prof. Dr.
University of Natural Resources and Applied Life Sciences
Institute of Microbial Genetics (IMiG)
E-mail: joseph.strauss(at)boku.ac.at 
Tel.: +43 1 47654 94420