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An Fe 2+ ‐ and α‐Ketoglutarate‐Dependent Halogenase Acts on Nucleotide Substrates
Author(s) -
Zhao Chunhua,
Yan Shan,
Li Qin,
Zhu Hucheng,
Zhong Zhiyu,
Ye Ying,
Deng Zixin,
Zhang Yonghui
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201914994
Subject(s) - nucleotide , nucleoside , chemistry , deoxyadenosine , chlorine , stereochemistry , biosynthesis , biochemistry , nucleic acid , phosphate , adenosine monophosphate , dna , organic chemistry , enzyme , gene
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 2+ ‐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 2+ ‐α‐ketoglutarate‐dependent halogenase that converts nucleotides into chlorinated analogues.