In the lab instead of from the whale intestine: Fragrance Ambrein produced naturally for the first time

Ambergris - also called amber, ambrox or ambergris - is considered the rarest and most expensive animal fragrance; depending on the quality, up to 50,000€ per kg. Because of its special aroma, described as aphrodisiac, woody and balsamic, and its ability to make fragrances last longer, it is hotly sought after by the perfume industry. "Ambrein serves as the main source of ambergris. This triterpene alcohol is formed as a metabolic product in the intestines of less than five percent of sperm whales," explains Harald Pichler, acib researcher and professor at the Institute of Molecular Biotechnology at Graz University of Technology. 

This mostly gray, wax-like substance presumably enters the sea through vomiting from the "shallows" of mammals, where it often drifts for decades before being washed ashore as flotsam. It is only through contact with salt water, sunlight and air that the odorous substances ambrox and ambrinol, which are responsible for the balanced fragrance, are formed from ambrein by oxidation. Due to the natural limitation of ambergris, the high industrial demand and the Washington Convention on International Trade in Endangered Species (WA), which prohibits trade in sperm whale products, ambergris has been produced synthetically since the late 1930s. 

Previous synthesis inefficient, expensive and environmentally harmful

Most chemical synthesis routes use plant-derived diterpenoids as starting materials, such as sclareol from S. sclarea, also called clary sage. This method has two disadvantages: First, the correct synthesis of these complex molecules has been extremely expensive and laborious. "Many individual, complex measures are necessary to achieve only about 4% yield. In addition, most production steps require the controversial use of environmentally harmful chemicals and high conversion temperatures as well as pressures," explains Sandra Moser, who is researching the topic in her dissertation. On the other hand, synthetic fragrances lack the natural, complex and rich scent mixture - which is why natural ambergris is still often used in high-quality perfumes. 

Naturally efficient

The Austrian Centre of Industrial Biotechnology (acib), in collaboration with the Graz University of Technology and industrial partner ACS International, has for the first time developed an entirely natural biosynthetic pathway that is one step ahead of conventional industrial production: "We have found a way to biosynthesize amrein, the natural precursor of ambergris, through a new metabolic pathway in yeast. Pichia pastoristo produce. This means that for the first time we can reproduce the entire fragrance spectrum, as occurs naturally in the sperm whale, by biosynthetic means," says Pichler. And we can do it cheaply, in previously unimagined quality and in larger quantities: "We can achieve a sevenfold higher yield from a simple carbon source such as glycerol or sugar with the help of an optimized enzyme, compared to previous enzymatic processes," Moser is pleased to report. 

The patent-pending innovation will be brought to industrial scale and thus market relevance in the near future. It is not yet possible to estimate when this will be. When it does, however, the process would have the potential to initiate an environmentally friendly turnaround in global perfume production and even add "olfactory complexity" to everyday products.

www.acib.at