Dong Changjiang, Huang Fanglu, Deng Hai, Schaffrath Christoph, Spencer Jonathan B, O'Hagan David, Naismith James H
Centre for Biomolecular Sciences, The University of St Andrews, Fife KY16 9ST, UK.
Nature. 2004 Feb 5;427(6974):561-5. doi: 10.1038/nature02280.
Fluorine is the thirteenth most abundant element in the earth's crust, but fluoride concentrations in surface water are low and fluorinated metabolites are extremely rare. The fluoride ion is a potent nucleophile in its desolvated state, but is tightly hydrated in water and effectively inert. Low availability and a lack of chemical reactivity have largely excluded fluoride from biochemistry: in particular, fluorine's high redox potential precludes the haloperoxidase-type mechanism used in the metabolic incorporation of chloride and bromide ions. But fluorinated chemicals are growing in industrial importance, with applications in pharmaceuticals, agrochemicals and materials products. Reactive fluorination reagents requiring specialist process technologies are needed in industry and, although biological catalysts for these processes are highly sought after, only one enzyme that can convert fluoride to organic fluorine has been described. Streptomyces cattleya can form carbon-fluorine bonds and must therefore have evolved an enzyme able to overcome the chemical challenges of using aqueous fluoride. Here we report the sequence and three-dimensional structure of the first native fluorination enzyme, 5'-fluoro-5'-deoxyadenosine synthase, from this organism. Both substrate and products have been observed bound to the enzyme, enabling us to propose a nucleophilic substitution mechanism for this biological fluorination reaction.
氟是地壳中含量第十三大的元素，但地表水中的氟化物浓度较低，且含氟代谢物极为罕见。氟离子在去溶剂化状态下是一种强亲核试剂，但在水中会紧密水合，实际上呈惰性。可用性低和缺乏化学反应活性在很大程度上使氟化物被排除在生物化学领域之外：特别是，氟的高氧化还原电位排除了用于氯离子和溴离子代谢掺入的卤过氧化物酶型机制。但含氟化学品在工业上的重要性日益增加，在制药、农用化学品和材料产品中都有应用。工业上需要使用专门工艺技术的活性氟化试剂，尽管这些工艺的生物催化剂备受追捧，但目前仅描述了一种能将氟化物转化为有机氟的酶。卡特利链霉菌能够形成碳 - 氟键，因此必定进化出了一种能够克服使用水性氟化物的化学挑战的酶。在此，我们报道了来自该生物体的首个天然氟化酶5'-氟-5'-脱氧腺苷合酶的序列和三维结构。已观察到底物和产物都与该酶结合，这使我们能够提出这种生物氟化反应的亲核取代机制。
