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. e successfully synthesized celastrol, a potent anti-obesity compound naturally occurring in the roots of the Thunder God vine (Tripterygium wilfordii), also known as “Seven Steps to Death” for its toxicity.
Synthetic biology represents the cutting-edge fusion of engineering and biology, with the goal of creating novel biological systems, molecules, and traits within living cells. This precise research domain is the focus of the Greek scientist’s work.
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. By transferring the genes and enzymes responsible for celastrol production from the plant into a non-toxic yeast strain, they successfully generated nearly pure celastrol, devoid of any 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.
“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 Kampranis Lab integrates fundamental biochemistry research with advanced protein engineering of biosynthetic enzymes and metabolic engineering of microorganisms suited for industrial applications. Their ultimate aim is to deliver sustainable solutions contributing to a more environmentally friendly 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 illustrates the versatility of yeast, a staple in the biotech industry, demonstrating its capacity for 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. More specifically, Dr. Kampranis’ research team has crafted 10 innovative isoprenoids, or terpenoids, serving as versatile building blocks akin to Legos. These breakthroughs open pathways to synthesizing a plethora of novel biological molecules with diverse shapes and structures.“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.
Upon discovering that certain newly developed isoprenoids possessed aromatic qualities, the researchers enlisted the expertise of odor specialists for characterization. Among them, four isoprenoids stood out for their distinct aromas, with one reminiscent of aged beer and another akin to a charred rose. Dr. Sotirios Kambranis is confident in the direct applicability of these novel isoprenoids 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 paclitaxel (taxol), used in chemotherapy, is another. 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
The majority of flavoring ingredients employed in today’s industries are isoprenoids. For instance, the familiar scents of basil, lavender, or mint primarily stem from typical isoprenoid molecules containing 10 or 15 carbon atoms. “We’ve spearheaded a groundbreaking reimagination of natural perfume manufacturing that could entirely eliminate the necessity for harvested aromatic compounds. Our overarching goal is to cater to the global market’s demand for a fragrance for every need,” remarks Professor Kampranis.
ofessor Kampranis and his colleagues at the University of Copenhagen are dedicated to forging a brighter future for our planet. Their collaborative endeavor focuses on sustainably producing aromatic compounds in yeast, thereby obviating the necessity to extract aromas from plants or resort to environmentally harmful and energy-intensive synthesis methods. This vision materialized in 2021 with the establishment of the University of Copenhagen spin-off company “Evodia”, where Professor Kampranis serves as co-founder and Head of R&D.
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.
Boost4Bio is privileged to have Dr. Kampranis as a member of its Scientific Advisory Board. His expertise and dedication are a great inspiration in our efforts to promote bioinnovation and bioentrepreneurship by establishing excellence in biomolecular engineering and synthetic biology.
For more insights into his work, delve into his recently published interview.