Remarkable discovery and collaborative effort have revealed a new type of triterpene, a group of organic compounds that are an important source of many drugs. Until now, it was believed that all triterpenes were derived from squalene, itself a type of triterpene. However, for the first time, researchers have witnessed biosynthesis, the formation of complex compounds from simple ones in living organisms, to triterpenes in fungi without the use of squalene. This important discovery opens up a whole new world of possibilities for pharmaceutical science.
Triterpenes are organic compounds found in abundance in animals, plants, microorganisms and even in our country. About 20,000 different triterpenes have been found and are widely used in cosmetics, dietary supplements and, most importantly, medicine, thanks to their valuable anti-inflammatory, anti-cancer, anti-diabetic and other properties. Until now, it was thought that all known triterpenes were generated from a precursor or common source, squalene.
However, as revealed in Nature, a collaborative effort between the University of Tokyo and KEK in Japan, Wuhan University in China, and Bonn University in Germany has found a new type of triterpene that does not require squalene.
“No one could have imagined this happening in nature.” This is the discovery of a new biosynthetic machine, ”said Professor Ikuro Abe of the Graduate School of Pharmaceutical Sciences at the University of Tokyo.
Often, several enzymatic reactions are needed to create complex molecular compounds, such as when our body uses squalene to create hormones and bile acids. However, in a single enzymatic reaction, a simple molecule called the C5 isoprene unit, or building block, was the trigger for building a very complex triterpene molecular structure.
The discovery was made almost by accident by the Wuhan University team, which was working on genome extraction to find new natural products. They did not necessarily look for triterpenes, but they did find new genes widely distributed in fungi. “They didn’t know the function of the genes,” Abe said. “So they did a characterization of these new genes, and one of them turned out to be the synthesis of triterpenes.” »
That’s when they asked the other teams to get involved. According to Abe, the University of Bonn team is good at chemistry, so they worked to elucidate the detailed mechanism of the enzymatic reaction, and researchers from the University of Tokyo and KEK applied their expertise in structural analysis. . He said that once you understand the structure, you can change it. “Change something here and there and see what happens.” We can understand the structure-function relationship. It’s like a puzzle, ”he explained.
“Chemistry in nature is more efficient than the chemical synthesis we use in industry.” That is why we are interested in biosynthetic processes in nature, ”said Abe. “Nature’s method is a better, cheaper and cleaner process.” We are trying to better understand how processes take place in nature so that we can recreate or redesign them in the laboratory, to obtain increasingly important and useful compounds. »
This new discovery is just the beginning. “Now that we have solved the structure of proteins, we are already manipulating biosynthetic machinery to try to produce more useful molecules, for example, for drug development,” said Abe.