Researchers develop new-to-nature fragrances

Environment and sustainability 22. nov 2022 2 min Professor Sotirios Kampranis Written by Kristian Sjøgren

Researchers have developed fragrances that no one has smelled before by manipulating yeasts to produce entirely new building blocks for life. The new building blocks are named after Danish artists and architects and can also be used to develop new types of medicine.

Life requires very few building blocks.

Proteins comprise 20 amino acids, DNA four nucleotides and fatty acids acetyl-coenzyme A.

The five-carbon isoprene unit is the building block for isoprenoids, which include hormones and membrane lipids such as cholesterol.

Isoprenoids have therefore always comprised a specific number of carbon atoms that is divisible by five, but researchers have now developed 10 new isoprenoid building blocks with 16 carbon atoms.

The researchers used these isoprenoid building blocks to create new biochemical molecules in the laboratory with new-to-nature fragrances.

The isoprenoids have many other potential uses than fragrances.

“Because the isoprenoids are so important to life, they can be developed into medicine and other products. Cortisol is an isoprenoid with anti-inflammatory properties, and paclitaxel, which is used in chemotherapy, is also an isoprenoid. Developing new types of isoprenoids opens the door to many interesting possibilities for making new types of medicine that are better or are unique,” explains a researcher involved in developing isoprenoids, Sotirios Kampranis, Professor of Biochemical Engineering at the Department of Plant and Environmental Sciences, University of Copenhagen.

The research has been published in Nature Communications.

Developing new building blocks for life

The researchers used a very special enzyme only present in certain bacteria that adds one extra carbon atom to 15-carbon isoprenoids and turns them into 16-carbon isoprenoids. The problem is that the enzyme can only incorporate the carbon in one specific place on an isoprenoid with 15 carbon atoms – three of the basic building blocks with five carbon atoms each.

The researchers therefore made mutants of the enzyme and incorporated the genetic code for the mutants into the DNA of a yeast, so that the mutant enzymes would place the extra carbon atom in different places on isoprenoids with 15 carbon atoms.

The researchers then manipulated the entire metabolism of the yeast so that it makes the new isoprenoids with 16 carbon atoms.

In the laboratory, the researchers made 10 new-to-nature isoprenoid building blocks. The isoprenoids have different shapes and structures and can act as Lego blocks in constructing many new types of biological molecules.

The researchers used these 10 building blocks to synthesise 28 new isoprenoids called non-canonical terpenes.

Sotirios Kampranis says that the various isoprenoids are all named after well-known artists and architects from Denmark. Blixenyl diphosphate is named after author Karen Blixen, hammershoyl diphosphate after painter Vilhelm Hammershøi, ancheryl diphosphate after painters Anna and Michael Ancher and jacobsenyl diphosphate after architect Arne Jacobsen.

“It was our privilege to name these new molecules, so we decided to name them after Danish artists and architects,” says Sotirios Kampranis.

Discovered four new fragrances

The researchers discovered that some of the newly developed isoprenoids had fragrant properties and established a panel of three trained odour assessors to characterise these new fragrances.

Four of the isoprenoids had a unique fragrance. One smelled like old beer, and another smelled like burnt roses. Blixenyl alcohol smelled woody.

Sotirios Kampranis says that the fragrance industry can immediately use the new isoprenoids.

“Fragrance experts are always looking for new fragrances that they can blend into perfumes and other products. They will determine whether they can create industrially useful fragrances with these new building blocks that cannot be created in any other way,” explains Sotirios Kampranis.

Further into the future, Sotirios Kampranis also thinks the isoprenoids have pharmaceutical potential.

“We can envision using these isoprenoids to produce new versions of existing medicines that are more effective or have fewer side-effects or to develop new types of medicine. Isoprenoids play an important role in biological functions, so new substances can be created and tested for, for example, anti-inflammatory or hormonal effects, but only the future will reveal this,” concludes Sotirios Kampranis.

Expanding the terpene biosynthetic code with non-canonical 16 carbon atom building blocks” has been published in Nature Communications. The Novo Nordisk Foundation awarded a grant to Sotirios Kampranis in 2016 for the project Transforming Yeast Organelles into Microfactories for the Compartmentalization of Complex Biosynthetic Pathways and an Ascending Investigator Grant in 2019 for the project Biotechnological Production of Structurally Complex Plant High-value Compounds.

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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