Stereospecific 2'-amination and 2'-chlorination of adenosine by Actinomadura in the biosynthesis of 2'-amino-2'-deoxyadenosine and 2'-chloro-2'-deoxycoformycin.
Stereospecific 2'-amination and 2'-chlorination of adenosine by Actinomadura in the biosynthesis of 2'-amino-2'-deoxyadenosine and 2'-chloro-2'-deoxycoformycin.
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DOI：
10.1016/0003-9861(89)90040-4
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发表时间：
1989-04
影响因子：
3.9
通讯作者：
R. Suhadolnik;S. Pornbanlualap;D. Baker;K. Tiwari;A. Hebbler
中科院分区：
文献类型：
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作者：
R. Suhadolnik;S. Pornbanlualap;D. Baker;K. Tiwari;A. Hebbler
2′-氨基-2 ′-脱氧腺苷和2′-氯-2 ′-脱氧柯福霉素（2′-CldCF）是马杜拉放线菌产生的两种核苷类抗生素。这两种核苷类抗生素的生物合成已被研究通过添加[U-14 C]腺苷与或不与未标记的腺嘌呤到培养物的Actinomadura。通过这种实验方法，有可能证明腺苷是2′-氨基-2 ′-脱氧腺苷和2′-CldCF生物合成的直接前体。这些结论基于以下观察结果：14 C在2′-氨基-2 ′-脱氧腺苷和2′-CldCF的无糖酸和戊呋喃糖基部分中的百分比分布与14 C在[U-14 C]腺苷的腺嘌呤和核糖基部分中的分布相似（即，48：52）添加到马杜拉放线菌的培养物中。实验上，14 C在（i）腺嘌呤：2 '-氨基-2'-脱氧腺苷的2-氨基-2-脱氧-β-d-呋喃核糖中的百分比分布为51：49;（ii）8-（R）-3，6，7，8-四氢咪唑并[4，5-d]-[1，3-二氮杂卓-8-o 1]：2 '-CldCF的2-氯-2-脱氧-β-d-呋喃核糖为45：55;和（iii）腺嘌呤：从马杜拉放线菌RNA中分离的腺苷的核糖42：58。通过将75 μmol未标记的腺嘌呤与[U-14 C]腺苷一起加入到产生核苷的马杜拉放线菌培养物中，进一步证明腺苷是生物合成2′-氨基-2 ′-脱氧腺苷和2′-CldCF的直接前体。14 C在苷元与2 '-氨基-2'-脱氧腺苷和2 '-CldCF糖部分的百分比分布分别为46：54和47：53;从马杜拉放射瘤RNA中分离的腺苷的腺嘌呤和核糖部分的14 C百分比分布为51：49。这些数据表明腺苷核糖基C-2′上的羟基被2′-氨基或2′-氯取代，形成2′-氨基-2 ′-脱氧腺苷或2′-CldCF，保留C-2′的立体构型。最后，马杜拉放线菌可利用培养基中的无机氯化物，如向培养基中加入[36 Cl]氯化物后分离出[36 Cl]2′-CldCF所示。讨论了C-2′羟基的区域选择性修饰以及氨基和氯基团的立体选择性插入的机理。
2′-Amino-2′-deoxyadenosine and 2′-chloro-2′-deoxycoformycin (2′-CldCF) are two nucleoside antibiotics produced byActinomadura. The biosynthesis of these two nucleoside antibiotics has been studied by the addition of [U-14C]adenosine with or without unlabeled adenine to cultures ofActinomadura. By this experimental approach, it is possible to demonstrate that adenosine is the direct precursor for the biosynthesis of 2′-amino-2′-deoxyadenosine and 2′-CldCF. These conclusions are based on the observation that the percentage distribution of14C in the aglyconic and pentofuranosyl moieties of 2′-amino-2′-deoxyadenosine and 2′-CldCF were similar to the distribution of14C in the adenine and ribosyl moieties of the [U-14C]adenosine (i.e., 48:52) added to cultures ofActinomadura. Experimentally, the percentage distribution of14C in the (i) adenine: 2-amino-2-deoxy-β-d-ribofuranose of 2′-amino-2′-deoxyadenosine is 51:49; (ii) 8-(R)-3,6,7,8-tetrahydroimidazo[4,5-d]-[1,3-diazepin-8-o1]:2-chloro-2-deoxy-β-d-ribofuranose of 2′-CldCF is 45:55; and (iii) adenine:ribose of the adenosine isolated from the RNA ofActinomadurais 42:58. Further proof that adenosine is the direct precursor for the biosynthesis 2′-amino-2′-deoxyadenosine and 2′-CldCF was demonstrated by the addition of 75 μmol of unlabeled adenine together with [U-14C]adenosine to nucleoside-producing cultures ofActinomadura. The percentage distribution of14C in the aglycon and the sugar moieties of 2′-amino-2′-deoxyadenosine and 2′-CldCF were 46:54 and 47:53, respectively; the percentage distribution of14C in the adenine and ribose moieties of the adenosine isolated from the RNA ofActinomadurawas 51:49. These data show that the hydroxyl on C-2′ of the ribosyl moiety of adenosine undergoes a replacement by a 2′-amino or a 2′-chloro group to form 2′-amino-2′-deoxyadenosine or 2′-CldCF with retention of stereconfiguration at C-2′. Finally,Actinomaduracan utilize inorganic chloride from the medium as demonstrated by the isolation of [36Cl]2′-CldCF following the addition of [36Cl]chloride to the culture medium. Mechanisms for the regioselective modification of the C-2′ hydroxyl group and stereospecific insertion of the amino and chloro groups are discussed.