Researchers discover bacteria producing unique molecules with surprising properties

Environment and sustainability 28. nov 2023 2 min Professor Sotirios Kampranis Written by Kristian Sjøgren

Despite 70 years of research, researchers have only now found that bacteria make thousands of molecules that should not exist in nature. A researcher says that the discovery is like finding a new spice drawer in your kitchen with completely new flavours and fragrances.

Researchers have been studying biomolecules called terpenoids for about 70 years and have established that almost all terpenoids in nature are based on backbones that contain multiples of five carbon atoms: 10, 15, 20 etc.

In biochemistry this is called the isoprene rule, which was first proposed by Nobel Laureate Leopold Ružička in 1953, and no one has questioned it since then.

A few years ago, however, a group of researchers hinted at the possibility that terpenoids with 16 carbon atoms might exist, and new research shows that this is not just conjecture but that nature has thousands of this type of terpenoids.

Since terpenoids are widely used in the perfume industry as fragrances and in the food industry as flavours and food colouring, a researcher behind the discovery compares this to finding a new spice drawer in the kitchen.

“We can use these terpenoids for producing completely new fragrances, polymers, biofuels and medicines. Knowing that they exist opens up many more opportunities to make commercially useful products in the future,” explains Sotirios Kampranis, Professor, Department of Plant and Environmental Sciences, University of Copenhagen.

The research has been published in Nature Chemical Biology.

Terpenoids have enormous potential

Terpenoids are a diverse group of specialised metabolites that are found everywhere in nature. Plants and bacteria use them to communicate with each other and to protect themselves.

Many terpenoids have fragrant properties, such as rose or menthol, but terpenoids are also used in biofuels, in food colouring such as the red colour in tomatoes, in cancer treatment such as paclitaxel and in antimalarial drugs such as artemisinin.

Many hormones are also terpenoids.

There are more than 70,000 types of terpenoids in nature, but until now researchers thought that all are based on the five-carbon isoprene building block.

“We can synthetically make terpenoids with different numbers of carbon atoms, but we did not know whether they also existed in nature,” says Sotirios Kampranis.

Genes revealed their ability to make terpenoids

To investigate the prevalence of terpenoids with a 16-carbon skeleton in nature, the researchers comprehensively reviewed all the available genetic information in bacteria – thousands of bacterial genome sequences from large databases.

The researchers looked for a sequence of genes showing that the bacteria can produce terpenoids with 16 carbon atoms.

In bacteria, genes that work together are located side by side in the genome, and the researchers searched for the gene for a methyltransferase adjacent to the gene for a terpene synthase.

Methyltransferase can change the number of carbon atoms in the terpene precursor to terpenoids, and terpene synthase makes the terpenoids.

Sotirios Kampranis explains that the methyltransferase first changes the number of carbon atoms in the substrate for forming terpenoids, and then the terpene synthase makes the terpenoid itself.

“This tells us that these bacteria can make terpenoids with 16 carbon atoms, and we found more than 700 bacterial genomes that can produce this type of terpenoid. This shows that not just one or two types of bacteria can make terpenoids with 16 carbon atoms but many can do this,” he adds.

Huge industrial potential

After identifying the 700 bacterial genomes, the researchers analysed terpenoids from 40 selected clusters of genes to map their structure. This enabled the researchers to guess what the terpenoids can be used for.

The terpenoids may be incorporated in many products with great industrial promise, and according to Sotirios Kampranis, other researchers may discover what they can be used for.

He imagines that, just as new spices would revolutionise cooking, the new terpenoids with 16 carbon atoms could turn out to revolutionise the development of medicines or new fragrances and flavours.

The researchers are also investigating some of the newly discovered terpenoids for useful properties and have now started to hunt for other types of terpenoids – such as those with 17 carbon atoms.

“The big question is what we can use all these terpenoids for. We will have to determine this in the future,” concludes Sotirios Kampranis.

I work in the area of Synthetic Biology/Metabolic Engineering, aiming to devise methods to produce high-value natural products in engineered organisms...

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