The identification of (3R,4S)-5-fluoro-5-deoxy-d-ribulose-1-phosphate as an intermediate in fluorometabolite biosynthesis in Streptomyces cattleya

(3R,4S)-5-Fluoro-5-deoxy-d-ribulose-1-phosphate (5-FDRulP) has been identified as the third fluorinated intermediate on the biosynthetic pathway to fluoroacetate and 4-fluorothreonine in Streptomyces cattleya. 5-FDRulP is generated after formation of 5′-fluoro-5′-deoxyadenosine (5′-FDA) and then phosphorolysis of 5′-FDA to 5-fluoro-5-deoxy-d-ribose-1-phosphate (5-FDRP) by the action of a purine nucleoside phosphorylase. An isomerase mediates the conversion of 5-FDRP to 5-FDRulP. The identity of the (3R,4S) diastereoisomer of 5-FDRulP was established by comparative 19F{1H} NMR studies whereby 5-FDRulP that accumulated in a cell free extract of S. cattleya, was treated with a phytase to generate the non-phosphorylated sugar, 5-fluoro-5-deoxy-d-ribulose (5-FDRul). This S. cattleya product was compared to the product of an in-vitro biotransformation where separately 5-fluoro-5-deoxy-d-ribose and 5-fluoro-5-deoxy-d-xylose were converted to 5-fluoro-5-deoxy-d-ribulose and 5-fluoro-5-deoxy-d-xylulose respectively by the action of glucose isomerase. It was demonstrated that 5-fluoro-5-deoxy-d-ribose gave the identical diastereoisomer to that observed from 5-FDRulP.

Graphical abstract(3R, 4S)-5-Fluoro-5-deoxy-D-ribulose-1-phosphate is identified as an intermediate in the biosynthesis of fluoroacetate and 4-fluorothreonine in Streptomyces cattleya.Figure optionsDownload full-size imageDownload as PowerPoint slide