![]() ![]() The occasion of his 80th Nobel anniversary allows the opportunity to celebrate his seminal contributions and reappraise the connection between terpenoid biochemistry and the existence of life on Earth. Ruzicka became increasingly interested in the possible link between the biogenetic isoprene rule and the question of life’s origin ( Eschenmoser 1990). In the same way as terpene chemistry is built on a common molecular plan involving isoprene, so too is terpenoid biology. The fundamental significance of the biogenetic isoprene rule to biology, immediately evident at the time, continues to become increasingly apparent. He also advanced a biochemical extension of the rule that became the basis of present day understanding of terpene biosynthesis, known as the ‘biogenetic isoprene rule’ ( Ruzicka 1953, 1959). The clue seemingly lies in their core chemical structure: they are all composed of multiples of a 5-carbon unit called isoprene (2-methyl 1,3-butadiene, isopentene), one of the most common organic chemicals on Earth ( Sharkey & Yeh 2001).Ģ019 marks the eightieth anniversary of the 1939 Nobel Prize in Chemistry awarded to Leopold Ruzicka (Ružička the French transcription ‘Rougitchka’ may assist in pronunciation), a Croatian national who worked extensively in Switzerland, for research that established the importance of the ‘isoprene rule’ in the elucidation of terpene chemical structures, including the classification of cholesterol and sex steroids as triterpenoids. Why so many structurally related compounds with such diverse functions should exist is yet to be explained. ![]() ![]() The terpenome (the compendium of all known terpenoids) is so vast that it accounts for nearly one-third of all compounds currently characterized in the ‘ Dictionary of Natural Products’ ( ) ( Christianson 2017). 2013): involvement so fundamental that as ancient lipids they may represent (along with DNA, RNA, and protein according to the central dogma), a fourth molecular strand of terrestrial life. Fossilized terpenes have been discovered in geological deposits billions of years old, signifying involvement in the very beginnings of life on Earth ( Ourisson & Albrecht 1992, Melendez et al. Terpenes (including sterols, steroids, and related aromatic hydrocarbons) are present in all known life forms where they pivotally impact on individual and population survival ( Summons et al. ‘ The structural similarities of the higher terpenes raise the question as to whether these compounds may have been formed according to a uniform principle in nature’ ( Ruzicka 1966) A harmonizing feature is that all known lifeforms (including bacteria) biosynthesize triterpenoid substances that are essential for cellular membrane formation and function, from which signaling molecules such as steroid hormones and cognate receptors are likely to have evolved. We address the potential abiotic generation of isoprene, the crucial role that polyprene terpenoids played in early membranes and cellular life, and emphasize that endocrinology from microbes to plants and vertebrates is firmly grounded on Ruzicka’s pivotal insights into the structure and function of terpenes. To redress the balance, we provide a historical and evolutionary perspective. Ruzicka also had a keen interest in the origin of life, but the pivotal role of terpenoids has generally been overshadowed by nucleobases, amino acids, and sugars. In the case of triterpenes, six C 5 isoprene units combine into C 30 squalene, which is cyclized into one of the signature carbon skeletons from which myriad downstream triterpenoid structures are derived, including sterols and steroids. The number of repeat isoprene units dictates the type of terpene produced (i.e., 2, monoterpene 3, sesquiterpene 4, diterpene, etc.). The rule declares terpenoids to be enzymatically cyclized products of substrate alkene chains containing a characteristic number of linear, head-to-tail condensed, C 5 isoprene units. Arguably his crowning achievement was the ‘biogenetic isoprene rule’, which helped to unravel the complexities of terpenoid biosynthesis. The year 2019 marks the 80th anniversary of the 1939 Nobel Prize in Chemistry awarded to Leopold Ruzicka (1887–1976) for work on higher terpene molecular structures, including the first chemical synthesis of male sex hormones. ![]()
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