“In Dr. Sotirios Kampranis’ laboratory in Copenhagen, a remarkable alchemy unfolds, yielding fragrances uncharted by human senses, yeast imbued with taste and scent, and a groundbreaking process, where toxicity-free, anti-obesity substances are born. This magical synthesis defies convention, representing a frontier of discovery, where science transcends into imagination.”

How does one get a useful substance in large quantitites without its typical toxicity? Dr. Sotirios Kampranis, a Professor of Biochemical Engineering in the Department of Plant and Environmental Sciences at the University of Copenhagen, achieves this feat through synthetic biology. He managed to produce celastrol, a chemical agent with strong anti-obesity action, which is naturally found within the roots of the plant “Thunder God vine” (Tripterygium wilfordii), which is also called “Seven Steps to Death” due to its toxicity.

Synthetic biology is the modern scientific combination of engineering and biology aiming to develop new biological systems, molecules, and characteristics in living cells, precisely the research field of the Greek scientist.

So, in the case of celastrol, the professor and his team mapped the pathway of 15 biochemical steps that the plant uses to form the substance and then produced celastrol synthetically in a tank with ordinary yeast used as a host organism. The scientists took the genes and enzymes involved naturally in the production of celastrol and placed them into another organism—a yeast that does not produce toxic substances. So, they got almost pure celastrol, without toxic compounds!

This was the first time this happened in the lab and led the University of Copenhagen to apply for a patent for the method published in the scientific journal Nature Chemistry, which is currently in discussions with potential partners for its commercialization.

The “key” to the green transition

“Synthetic biology, i.e., the ability to precisely modify organisms genetically to produce various bio-products we use today, turning simple biomass into valuable products, holds the key to the “green transition,” comments Dr. Kampranis.

The research team in the Kampranis Lab combines basic research in biochemistry with protein engineering of biosynthetic enzymes and metabolic engineering of industrially amenable microorganisms, to provide sustainable solutions for a greener planet.

“There is a high demand for natural perfumes and cosmetics today, but the production of many valuable bio-components is neither ‘green’ nor sustainable,” he points out and continues: “The rose, lemon and pine needle scents, but also many dyes, pesticides and biopolymers are usually produced through energy-intensive, industrial chemical processes by using petrochemicals and toxic catalysts and solvents as raw materials, or are derived from over-cultivation and over-harvesting of plants. Other bio-ingredients, such as proteins from milk, egg, or meat, require animal rearing, significant land areas and huge amounts of energy and are responsible for a large proportion of total greenhouse gas emissions. The future of our planet depends on replacing current technologies to produce these bio-components with new, sustainable and, at the same time, economical methods” he adds.

Professor Kampranis takes the example of yeast, which is widely used in the biotech industry, for the large-scale production of naturally occurring substances: “By using yeast we don’t need plant cultivation, transportations over long distances, or using chemicals and energy. If we want to make our lives more sustainable and fight climate change, this is one way to produce flavors and aromas”, he adds.

Fragrances that have never been experienced

By manipulating yeasts to produce entirely new fundamental building blocks of life, the Kampranis Lab developed fragrances that no one had ever smelled before and gave them names of Danish artists and architects, such as Blixen (from the writer Karen Blixen), Hammersen (from the painter Vilhelm Hammershøi), Ancheren (from the painters Anna and Michael Ancher) and Jacobsen (from the architect Arne Jacobsen).

Specifically, Dr Kampranis research team created 10 new isoprenoids, or terpenoids, building blocks with different shapes and structures that can act as Legos for the synthesis of many new types of biological molecules. “While isoprenoids are compounds made up of a specific number of carbon atoms that is a multiple of 5 (divisible by five), the new building blocks we developed are made up of 16 carbon atoms. With these new building blocks we created in the Lab new biochemical molecules with unprecedented aromas. And this whole process was carried out again in yeast”, describes the professor.

When the researchers discovered that some of the newly developed isoprenoids had aromatic properties, they invited odor experts to characterize them. Four of the isoprenoids had a unique aroma, one smelled like old beer and the other one like a burnt rose. Dr. Sotirios Kambranis is sure that these new isoprenoids can be used directly in perfumery.

This research was published in the journal Nature Communications in 2022.

Apart from fragrances, isoprenoids also include chemical molecules, such as hormones and cell membrane lipids, such as cholesterol. Cortisol is an isoprenoid with anti-inflammatory properties, and another example is paclitaxel (taxol), which is used in chemotherapy. The development of new types of isoprenoids opens new roads to the creation of new types of drugs that are better or even unique.

Research and…Evodia

Most of the flavoring ingredients used today in industry are isoprenoids. The basil, lavender, or mint aroma, for example, is mostly typical isoprenoid molecules with 10 or 15 carbon atoms. “We have made a pioneering reinvention of natural perfume production that can completely replace the need for harvested aromatic compounds. Our long-term ambition to supply the global market with a fragrance for everything…” says Professor Kampranis.

Professor Kampranis and his colleagues at the University of Copenhagen join efforts to create a better future for our planet by producing aromatic compounds in yeast in a sustainable way and, thus, eliminating the need to extract aromas from plants or to synthesize them through harmful and energy-intensive processes. This effort took shape in 2021 in the spin-off company of the University of Copenhagen ‘Evodia’, co-founder and R&D Head of which is Professor Kampranis.

In reference to the name “Evodia”, translated to “pleasant aroma” in Greek: “It is associated with the inspiring heritage of my Greek grandmother, who used herbs both in food and for medicinal purposes. Our goal is to create a sustainable future where everyone can enjoy great taste and smell without depleting natural resources” emphasizes Dr. Kampranis.

Professor Sotirios Kampranis, through his recent presentation at the Athens Science Festival 2024, conveyed a compelling message underscoring that synthetic biology marks the onset of a green transition.

Twin4Promis is grateful to have Dr. Kampranis on board as an advanced partner in our project. His expertise and dedication have greatly enriched our efforts.

Learn more about his work through his recently published interview (in Greek).