Biological systems are a rich reservoir of chemistry. In the process of “bioprospecting”, researchers tap into nature’s vast chemical space and identify small-molecule natural products that can be developed into products which benefit society. Many such compounds have been identified in recent years and had key impacts on a range of industries, from pharmaceutical to cosmetic. 

Increasingly, natural product researchers have been turning to the ocean as a rich yet relatively untapped source of interesting compounds. However, the journey from identifying to commercializing a natural product is complex and requires expertise in several domains of chemistry and the life sciences.  

To accelerate the development of marine natural products, EU-OPENSCREEN is collaborating with 12 partners across four European Research Infrastructures in the EU-funded Horizon Europe project “EUREMAP” (Grant ID 101131663) to establish a complete pipeline for marine bioprospecting. This pipeline, which is currently under development, will be available to natural product researchers across Europe and the world.  

The Helmholtz Centre for Infection Research (HZI), an EU-OPENSCREEN partner site and EUREMAP collaborator, recently published a drug discovery study which was made possible by a portion of the nascent EUREMAP pipeline – representing an early success for EUREMAP and EU-OPENSCREEN's contribution to the marine bioprospecting.  

This project built on natural product researchers from the Technical University of Braunschweig and the Scripps Institution of Oceanography in San Diego, California, who discovered an interesting class of volatile compounds produced by the marine bacteria Salinispora arenicola. These compounds, known as salinilactones, have a unique structure and seemed to inhibit the growth of bacteria and other organisms. However, the exact mechanisms of these effects were unknown.  

To better understand how salinilactones affect biological systems, the TU Braunschweig team collaborated with Prof. Dr Mark Brönstrup at the HZI Department of Chemical Biology, whose group specializes in characterizing novel compounds. Through a suite of advanced chemoproteomics, mass spectrometry, and enzyme assays, they found that salinilactones inhibit protein disufide isomerases (PDIs) and thioredoxin (TRX1) with high selectivity. Both proteins are implicated in diseases such as cancer, pointing to salinilactones as a promising new therapeutic direction for these diseases. This study is also one of the first to pinpoint a molecular target for a volatile marine natural product, indicating a bright future for investigation into similar compounds.  

Further, this project was a successful initial demonstration of the EUREMAP pipeline’s value for marine natural product development. “The EUREMAP pipeline is ideally suited to identify more novel and unusual marine compounds with interesting bioactivities,” Mark shared with us. “We hope that we can apply our expertise to decipher how these compound work and why they are so active.” 

EU-OPENSCREEN is supporting the EUREMAP pipeline through five affiliated partners offering a range of services to synthesize and study marine natural products: 

• Helmholtz Centre for Infection Research (HZI; Braunschweig, DE) 

• Fundacion MEDINA (Granada, ES) 

• National Research Council of Italy (CNR; Naples, IT) 

• Arctic University of Norway (UiT; Tromsø, NO) 

• SINTEF (Trondheim, NO) 

Learn more about the EUREMAP project at https://euremap.eu. 

Read the full study on volatile salinilactones as inhibitors of protein disulfide isomerases: 

K. Jerye, H. Lüken, A. Steffen, C. Schlawis, L. Jänsch, S. Schulz, M. Brönstrup 

Activity-Based Protein Profiling Identifies Protein Disulfide-Isomerases as Target Proteins of the Volatile Salinilactones 

Adv. Sci. 2024, 11, 2309515. https://doi.org/10.1002/advs.202309515