The deazapurine biosynthetic pathway revealed: in vitro enzymatic synthesis of PreQ(0) from guanosine 5'-triphosphate in four steps.
The deazapurine biosynthetic pathway revealed: in vitro enzymatic synthesis of PreQ(0) from guanosine 5'-triphosphate in four steps.
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DOI：
10.1021/bi900400e
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发表时间：
2009-05-12
期刊：
影响因子：
2.9
通讯作者：
Bandarian, Vahe
中科院分区：
文献类型：
--
作者：
McCarty, Reid M.;Somogyi, Arpad;Lin, Guangxin;Jacobsen, Neil E.;Bandarian, Vahe
含有脱氮嘌呤的次级代谢产物包含广泛的结构多样的核苷类似物，其在整个生物学中发现，包括由链霉菌属细菌物种产生的各种抗生素和高度修饰的tRNA碱基曲马核苷和古核苷。尽管早期对脱氮嘌呤作为抗生素、抗病毒剂和抗病毒剂感兴趣，但40多年来，脱氮嘌呤生产的生物合成途径在很大程度上仍然难以捉摸。在这里，我们提出了第一个在体外制备的脱氮嘌呤核苷，preQ 0，通过连续的行动，四个酶。该途径包括最近鉴定的生物合成中间体6-羧基-5，6，7，8-四氢蝶呤通过B催化的不寻常的转化转化为新的中间体7-羧基-7-脱氮鸟嘌呤（CDG）。subtilis QueE是自由基SAM酶超家族的成员。随后通过B将CDG上的羧酸酯部分转化为腈以产生preQ 0。subtilis QueC或S. rimosus ToyM在ATP依赖性反应中，其中氨作为氮源。这里提出的结果是一致的，与早期的放射性示踪剂研究脱氮嘌呤生物合成，并提供了一个统一的途径，生产脱氮嘌呤在自然界中。
Deazapurine-containing secondary metabolites comprise a broad range of structurally diverse nucleoside analogs found throughout biology including various antibiotics produced by species of Streptomyces bacteria and the hypermodified tRNA bases queuosine and archaeosine. Despite early interest in deazapurines as antibiotic, antiviral, and antineoplastic agents, the biosynthetic route toward deazapurine production has remained largely elusive for more than 40 years. Here we present the first in vitro preparation of the deazapurine nucleoside, preQ0, by the successive action of four enzymes. The pathway includes the conversion of the recently identified biosynthetic intermediate, 6-carboxy-5,6,7,8-tetrahydropterin, to a novel intermediate, 7-carboxy-7-deazaguanine (CDG), by an unusual transformation catalyzed by B. subtilis QueE, a member of the radical SAM enzyme superfamily. The carboxylate moiety on CDG is converted subsequently to a nitrile to yield preQ0 by either B. subtilis QueC or S. rimosus ToyM in an ATP-dependent reaction, in which ammonia serves as the nitrogen source. The results presented here are consistent with early radiotracer studies on deazapurine biosynthesis and provide a unified pathway for the production of deazapurines in nature.
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影响因子：
2.9
作者：
Cicmil, Nenad;Huang, Raven H.
通讯作者：
Huang, Raven H.
影响因子：
14.9
作者：
KASAI, H;KUCHINO, Y;NISHIMURA, S
通讯作者：
NISHIMURA, S
影响因子：
2.9
作者：
UEMATSU, T;SUHADOLN.RJ
通讯作者：
SUHADOLN.RJ
DOI：
10.1073/pnas.0408056102
发表时间：
2005-03-22
影响因子：
11.1
作者：
Van Lanen, SG;Reader, JS;Iwata-Reuyl, D
通讯作者：
Iwata-Reuyl, D
影响因子：
2.9
作者：
McCarty, Reid M.;Somogyi, Arpad;Bandarian, Vahe
通讯作者：
Bandarian, Vahe