New combination of methods shortens search for bioactive compounds

Cyanobacteria from Caribbean coral reefs produce a group of natural substances that effectively inhibit digestive enzymes. This was discovered by an international research collaboration led by Marburg-based pharmacist Professor Dr. Raphael Reher and Tübingen-based biochemist Dr. Daniel Petras, using a newly developed combination of methods to systematically identify the large number of potential active pharmaceutical agents from complex environmental samples. The team reports its findings in the scientific journal Nature Communications.

Microorganisms produce numerous metabolites whose usefulness for human purposes remains to be discovered. To determine the mode of action of such substances and their molecular structure, they must first be obtained in pure form. "Together with the complete structural elucidation, this process usually takes months to years," explains senior author Daniel Petras, who heads a Junior Research Group at the Cluster of Excellence "Controlling Microbes to Fight Infections" (CMFI) at the University of Tübingen. "This time-consuming process represents a significant bottleneck for the systematic search for new cures from natural products," adds first author Raphael Reher, who recently began teaching pharmaceutical biology and biotechnology at Marburg's Department of Pharmacy.

To accelerate the identification of pharmaceutically promising substances, the scientists involved combined several advanced methods. In this way, the team succeeded in combining two goals: On the one hand, the effective separation of molecules leads to sorting apart the components of the crude extract; on the other hand, the interactions of binding partners can be traced.

To this end, the research group made particular use of a novel approach in mass spectrometry: Whereas in mass spectrometry proteins are usually decomposed into their constituent parts, native mass spectrometry is concerned precisely with preserving the spatial structure of the protein, because this is what determines its function.

Petras and Reher developed the experimental setup while they were still postdoctoral fellows together at the University of California San Diego in the United States.  "The project is a good example of how complex cross-border research collaboration should work," Petras points out. "I'm very proud of our international team collaborated across disciplines, such as natural products research, analytical chemistry and informatics, to make the study possible."

"The fact that we have now been able to establish and further develop the technology here, thanks to the excellent infrastructure and new collaborations in Tübingen and Marburg, is an important point. This has led to the successful completion of the study and will be the basis for our future research," adds Reher.