The identification of 5′-fluoro-5-deoxyinosine as a shunt product in cell free extracts of Streptomyces cattleya

• Published in: Bioorganic chemistry Vol. 33; no. 5; pp. 393 - 401
• Main Authors: Cobb, Steven L., Deng, Hai, Hamilton, John T.G., McGlinchey, Ryan P., O’Hagan, David, Schaffrath, Christoph
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2005
• Subjects: 4-Fluorothreonine; 5′-Fluoro-5′-deoxyadenosine; 5′-Fluoro′-deoxyinosine; Biotransformation; Cattleya; Cell-Free System; Dimethyl Sulfoxide; Fluorinase; Fluoroacetate; Fluorometabolite; Inosine - analogs & derivatives; Inosine - analysis; Magnetic Resonance Spectroscopy; Streptomyces; Streptomyces - chemistry; Streptomyces cattleya; Fluorinase; 5′-Fluoro-5′-deoxyadenosine; 5′-Fluoro′-deoxyinosine; Fluoroacetate; Fluorometabolite; 4-Fluorothreonine
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2005.07.002

5′-Fluoro-5′-deoxyinosine (5′-FDI) is identified as an adventitious side product that accumulates in cell free incubations of SAM and fluoride ion in Streptomyces cattleya. 5′-FDI was identified by a combination of isotopic labelling studies and co-synthesis studies as well as enzymatic degradation. Although it is an efficiently generated end product of the cell free incubations, 5′-FDI is not a biosynthetic intermediate and it does not accumulate as a fluorometabolite with fluoroacetate and 4-fluorothreonine in whole cell incubations of S. cattleya. Clearly the purine deaminase which converts 5′-fluoro-5′-deoxyadenosine (5′-FDA) to 5′-FDI in the cell free extract does not come into contact with 5′-FDA in whole cells, suggesting some level of compartmentalisation in cells of S. cattleya. The biotransformation of 5′-FDI from fluoride ion extends the range of organofluorine products, beyond biosynthetic intermediates, that can be generated by this system, for applications such as enzymatic labelling with fluorine-18 for positron emission tomography applications.