Biocatalytic Application of 6-Oxo Camphor Hydrolase: a New Enzyme-Catalysed Desymmetrisation Reaction

Erwin Schrödinger Fellowship J 1928 Biocatalytic Application of 6-Oxo Camphor Hydrolase Ulrike STRAUSS 26.6.2000 The aim of this project will be to investigate the potential utility of a new type of hydrolase enzyme, 6-oxo, camphor hydrolase, for the desymmetrisation of symmetrical 1,3-dicarbonyl compounds. This enzyme, which is derived from the bacterium Rhodococcus sp. NCIMB 9784 grown on (lR)-(+)-camphor, catalyses the desymmetrisation of its native substrate 6-oxo camphor to a chiral keto acid, alpha-campholinic acid, of high optical purity. The enzyme has recently been isolated and characterized by the group of Nicholas J. Turner in Edinburgh, UK. Further research is now required to investigate the factors that control both substrate recognition and chiral transformation by the enzyme. This investigation will involve the synthesis of a wide range of 1,3- dicarbonyl compounds, their presentation to the enzymatic system and the chiral analysis of the products formed. The application of any chiral intermediates generated by these new enzymatic processes to asymmetric synthesis will then be explored. Future prospects would be the investigation of the primary structure of the enzyme via gene cloning in order to initiate structure function studies that will shed light on the mechanism of action of this rare class of enzymes. In summary, this project seeks to broaden the understanding and application of enzymes in the process of molecular desymmetrisation in organic synthesis. It would also endeavour to provide new mechanistic information about a rarely studied and potentially very useful class of enzymes and their application in synthetic bioorganic chemistry for the first time.