Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071, P. R. China.
Angew Chem Int Ed Engl. 2020 Jun 8;59(24):9478-9484. doi: 10.1002/anie.201914994. Epub 2020 Apr 1.
While halogenated nucleosides are used as common anticancer and antiviral drugs, naturally occurring halogenated nucleosides are rare. Adechlorin (ade) is a 2'-chloro nucleoside natural product first identified from Actinomadura sp. ATCC 39365. However, the installation of chlorine in the ade biosynthetic pathway remains elusive. Reported herein is a Fe -α-ketoglutarate halogenase AdeV that can install a chlorine atom at the C2' position of 2'-deoxyadenosine monophosphate to afford 2'-chloro-2'-deoxyadenosine monophosphate. Furthermore, 2',3'-dideoxyadenosine-5'-monophosphate and 2'-deoxyinosine-5'-monophosphate can also be converted, albeit 20-fold and 2-fold, respectively, less efficiently relative to the conversion of 2'-deoxyadenosine monophosphate. AdeV represents the first example of a Fe -α-ketoglutarate-dependent halogenase that converts nucleotides into chlorinated analogues.
虽然卤代核苷通常被用作抗癌和抗病毒药物，但天然存在的卤代核苷却很少见。阿得氯林（ade）是一种 2'-氯核苷天然产物，最初从 Actinomadura sp. ATCC 39365 中鉴定出来。然而，ade 生物合成途径中氯的安装仍然难以捉摸。本文报道了一种 Fe-α-酮戊二酸卤代酶 AdeV，它可以在 2'-脱氧腺苷单磷酸的 C2'位置安装一个氯原子，生成 2'-氯-2'-脱氧腺苷单磷酸。此外，2'，3'-二脱氧腺苷-5'-单磷酸和 2'-脱氧肌苷-5'-单磷酸也可以被转化，尽管相对于 2'-脱氧腺苷单磷酸的转化，其效率分别低 20 倍和 2 倍。AdeV 代表了第一个将核苷酸转化为氯化类似物的 Fe-α-酮戊二酸依赖性卤代酶的例子。
