Wolf Prize Laureate in Medicine 1986
The Medicine Prize Committee unanimously decided that the Wolf Prize in Medicine for 1986 be awarded to:
Osaka Medical College
“for the discovery of the oxygenase enzymes and elucidation of their structure and biological importance.”
Professor Osamu Hayaishi made outstanding and pioneering contributions to biomedical sciences and enzymology by his discovery of oxygenases. These enzymes are widely distributed in nature and represent a unique group of respiratory enzymes that catalyze the direct incorporation of molecular oxygen into various substrates. They play crucial roles in:
1) biosynthesis and degradation of certain amino acids,
2) metabolic disposal of synthetic compounds such as various drugs and food additives,
3) decomposition of various compounds responsible for pollution by air, water or soil microorganisms.
Prior to the discovery of oxygenases by Hayaishi in 1955, the only known mechanism of biological oxidation was the ‘dehydrogenation’ theory proposed by Wieland in 1920, namely the transfer of hydrogen atoms, or electrons. With Hayaishi´s demonstration of the biological fixation of molecular oxygen, a new concept of oxidation was introduced. The existance of ‘oxygenases’,as Hayaishi termed the enzymes which catalyze such oxygen-fixation reactions, has been confirmed in a large number of laboratories and the number of known oxygenases now exceeds several hundreds.
Hayaishi and coworkers discovered and characterized more than 20 oxygenases, crystallized four of them and made extensive studies concerning their structure and properties. Some of these enzymes, have been shown to be widely distributed in soil and air-born microorganisms and to playa vital role in the degradation of a variety of synthetic and natural compounds in nature. Thus, Hayaishi not only opened up a new area of research but also made fundamental contributions to our understanding of the structure and the reaction mechanism of the unique group of enzymes.
A number of oxygenases characterized by Hayaish1 play crucial roles in the metabolism of amino acids such as tryptophan, lysine, histidine and others. His studies on these amino acids have resulted in the elucidation of several new and physiologically important metabolic pathways, both in mammals and microorganisms. Furthermore, studies on the individual oxygenases involved have yielded basic information on the regulatory mechanism, which controls their activities. In addition to these studies, his work extends to oxygenases involved in the metabolism of other biologically important compounds, such as prostaglandins, vitamin A and carcinogenic hydrocarbons, that incite the development of malignancy.
His latest work demonstrated that interferon (a protein produced by intact animal cells when infected with viruses) induces indoleamine 2,3 dioxygenase, which degrades and depletes tryptophan, thereby inhibiting the growth of viruses and tumors. These experiments clearly demonstrated that oxygenase plays a crucial role in the interferon action, which acts to inhibit viral reproduction and to induce resistance in host cells.