Key enzymes for synthesizing natural products

Plants, fungi and bacteria produce natural products that function as defenses against predators and competitors. In medicine, these compounds have applications such as antibiotics, cancer drugs and cholesterol reducers. The team working with Associate Professor Robin Teufel and Dr. Britta Frensch from the Institute of Biology II of the Faculty of Biology at the University of Fribourg and researchers from ETH Zürich in Switzerland were able to shed light on the key role of three enzymes involved in the synthesis of a class of natural products. The researchers published their findings in Nature Communications.

Actinobacteria produce many natural products, such as those known as aromatic polyketides. The Freiburg researchers examined how actinobacteria, aided by enzymes, were able to synthesize these bioactive substances from simple molecular components. Teufel and his team were able to highlight the key roles played by three enzymes in the biosynthesis of rubromycins, which are among the most structurally complex aromatic polyketides.

The researchers found that the enzymes radically restructure a precursor chemical molecule. This process allows them to create the carbon skeleton of rubromycins, which is the key to the various pharmacological effects of these compounds. Using chemical and biochemical methods, the researchers were able to take a closer look at the functions of the enzymes and identify several previously unknown intermediates in rubromycin biosynthesis.

Teufel explains, "We have made important discoveries about how these enzymes control the formation of complex natural products in microorganisms. These findings could play a central role in the application of bioengineering to make new types of bioactive rubromycin-polyketides."