Chapter 18 - Biological Fluorination in Streptomyces cattleya: The Fluorinase

Abstract

This chapter reviews the recent developments on research into bacterial C-F bond forming enzyme. The fluorinase enzyme was isolated from Streptomyces cattleya in 2002 and shown to catalyze the conversion of fluoride ion and S-adenosyl-L-methionine (SAM) to 5'-fluoro-5'-deoxyadenosine (5'-FDA) and L-methionine. Subsequently, the enzyme has been the subject of cloning, crystallization mechanism and substrate specificity studies. S. cattleya is the producing organism for the b-lactam antibiotic, thienamycin 3, and during the efforts by Merck to improve the production titre of this antibiotic, they discovered a novel antibiotic activity when a particular soya protein was used in the fermentation nutrient. It subsequently transpired that the soya protein had significant levels of fluoride ion and that the novel antibiotic activity was due to 4-fluorothreonine (4-FT) 2 production. Positron emission tomography (PET) is an important non-invasive diagnostic method in the clinic for imaging tumors. The two most widely used positron emitting isotopes in PET are 11C (t1/2—11 min) and 18F (t1/2—110 min). Enzymes have not been used in PET ligand syntheses due to the virtual absence of appropriate enzymes to utilize the common sources of these isotopes. Fluoride ion is the preferred starting point because [18F]-fluoride is generated directly by the cyclotron in very high specific radioactivity (typically GBqs). Due to the relatively short half lives of the isotopes, syntheses methods for PET should ideally be rapid and incorporate isotope of high specific radioactivity.