ETH Zurich chemist Freideriki Michailidou is developing novel processes for the sustainable production of fragrance ingredients. As a first step, she studied the scents of rare aromatic plants that grow only on Mount Olympus in Greece.
How a product smells affects how we respond to it. So it comes as no surprise that fragrances are an integral part of more than 25 product categories - from cosmetics such as perfumes, creams and deodorants to household products like detergents and cleaners. Indeed, the global fragrance ingredience market was worth over eight billion dollars in 2021.
Of the approximately 3,000 fragrance ingredients that exist, the vast majority are not produced sustainably. They are based on fossil resources and usually rely on energy-intensive production methods, or in rare cases involve the use of materials obtained from rare plants and endangered animals.
Freideriki Michailidou believes it's about time for this to change. The 31-year-old Greek native works as a lecturer and researcher in the Laboratory of Toxicology run by ETH Zurich Professor Shana Sturla and was most recently a junior fellow at Collegium Helveticum. Michailidou wants to use the latest biochemical techniques to create new - and most importantly, sustainable - fragrances from natural and renewable raw materials.
This allows her to combine her passion for perfumes, which she makes in her free time from essential oils, with her professional scientific interest in green chemistry: "I can't and don't want to imagine a world without perfumes, but future production should be made more environmentally benign."
An early fascination for natural sciences
Freideriki Michailidou, Frida to her friends, grew up in the city of Ioannina in northern Greece. By the time she was nine, she had already developed a love for natural science, playing with her chemistry set and devouring every issue of National Geographic she could get her hands on. Her mother is a teacher and encouraged her to pursue her passion for science. "I knew from an early age that I wanted to become either a chemist or a biologist," Michailidou says.
She ultimately settled on chemistry, studying in Thessaloniki, Lyon and St. Andrews, where she researched biocatalysis in the course of writing her doctoral thesis. This is a technology that uses enzymes and living microorganisms as catalysts for chemical reactions. "In nature, enzymes facilitate a host of chemical reactions. This is an inherent property of enzymes that we can make use of in the lab," Michailidou says.
Biocatalysis was suddenly on everyone's lips back in 2018, when Frances Arnold shared the Nobel Prize in Chemistry with George Smith and Gregory Winter for her work on the directed evolution of enzymes. Many people still hope that this is what will make the chemical industry greener. One of them is Michailidou, who after working for a brief spell in industry and then as a postdoc in Münster, came to ETH Zurich as a Marie Skłodowska-Curie Fellow in 2019. Even back then, it was already Michailidou's ambition to use biocatalysis to produce new, sustainable fragrances.
Perfumes made from rare flowers
To expand the range of available fragrances, Michailidou chose an arduous path. She decided to analyse and mimic the properties of rare flowers that grow only on Greece's highest mountain, Mount Olympus, where they emit unique fragrances.
Nobody else had ever decoded the scents of these particular flowers. In addition to growing at over 2,100 metres above sea level, they are protected under conservation laws that prohibit people from picking them. "The challenge was to collect the volatile scent molecules, which normally attract bees and other pollinators, without damaging the plant," Michailidou explains.
To tackle this challenge, she scaled Mount Olympus this past summer. She took along one of the ETH Biocommunication group's headspace traps, a device equipped with a glass bell or a plastic bag, which is placed carefully over a plant. The scent molecules can then be captured and stored for subsequent analysis in the lab.
Michailidou says that her time on Mount Olympus was incredibly special: "I felt like one of those pioneering natural scientists I read about all through my childhood."
The promise of biocatalysis
Back at ETH, Michailidou decoded the molecules in the lab. Using a device that uses gas chromatography coupled to mass spectrometry, she can identify natural fragrances that have never been examined before. Only once the molecular structures of the new scents have been unlocked can she begin to chemically mimic them.
To do this, Michailidou is developing a biocatalysis technique that harnesses natural and renewable raw materials. In contrast to many synthetic catalysts, biocatalysts offer exquisite selectivity and are eco-friendlier because they work at lower temperatures and pressures and consume less energy.
"Not only do the right enzymes make producing fragrances cleaner and safer, they also speed up the whole process," Michailidou says. To find these enzymes, she uses a testing method modelled on natural evolution, but also incorporates computer-aided protein design and machine learning.
No testing on animals
There is yet another advantage to Michailidou's approach. The allergy potential of fragrance ingredients can be determined without any animal testing whatsoever. This is because they are tested in vitro in the lab using isolated skin cells.
"We've made the safety considerations part of our design process," Michailidou says. Any molecules that are toxic or that could trigger an allergic reaction are not used in the first place.
The dream of inventing perfumes
Michailidou believes that more and more biocatalytic methods will lend themselves well to industrial production processes, including applications in the pharmaceutical and food sectors. But there's still a lot of work to do because biocatalysis is currently still too expensive compared to synthetic alternatives.
Nevertheless, Michailidou has no doubt that the demand for sustainably produced fragrances is high. To substantiate this impression, she and ETH Zurich's Consumer Behaviour research group intend to find out what consumers actually think about natural perfumes and fragrances. Depending on these results, Michailidou could also see herself founding her own start-up. "That would be a dream come true," she says.
