Onega Mayca, McGlinchey Ryan P, Deng Hai, Hamilton John T G, O'Hagan David
School of Chemistry and Centre for Biomolecular Science, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK.
Bioorg Chem. 2007 Oct;35(5):375-85. doi: 10.1016/j.bioorg.2007.04.001. Epub 2007 Jun 14.
(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 (19)F{(1)H} 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.
(3R,4S)-5-氟-5-脱氧-D-核糖-1-磷酸（5-FDRulP）已被确定为产紫链霉菌中氟乙酸和4-氟苏氨酸生物合成途径上的第三种氟化中间体。5-FDRulP是在5'-氟-5'-脱氧腺苷（5'-FDA）形成后产生的，然后通过嘌呤核苷磷酸化酶的作用将5'-FDA磷酸解为5-氟-5-脱氧-D-核糖-1-磷酸（5-FDRP）。一种异构酶介导5-FDRP向5-FDRulP的转化。通过比较（19）F{(1)H} NMR研究确定了5-FDRulP的（3R,4S）非对映异构体的身份，即对产紫链霉菌无细胞提取物中积累的5-FDRulP用植酸酶处理以生成非磷酸化糖5-氟-5-脱氧-D-核糖（5-FDRul）。将这种产紫链霉菌产物与体外生物转化产物进行比较，在体外生物转化中，5-氟-5-脱氧-D-核糖和5-氟-5-脱氧-D-木糖分别通过葡萄糖异构酶的作用转化为5-氟-5-脱氧-D-核糖醇和5-氟-5-脱氧-D-木酮糖。结果表明，5-氟-5-脱氧-D-核糖产生的非对映异构体与从5-FDRulP中观察到的相同。
