Unique O-ribosylation in the biosynthesis of butirosin
Unique O-ribosylation in the biosynthesis of butirosin
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DOI：
10.1016/j.bmc.2007.04.040
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发表时间：
2007-07-01
影响因子：
3.5
通讯作者：
Eguchi, Tadashi
中科院分区：
文献类型：
--
作者：
Kudo, Fumitaka;Fujii, Takuya;Eguchi, Tadashi
利用比较遗传学的方法，从环状芽孢杆菌SANK72073的丁松素生物合成基因簇(BTR)中鉴定出一个或多个BtrA、BtrL、BtrP和BtrV蛋白参与O-核糖基化过程，导致核糖化反应的关键中间体核糖素的形成以及相关的抗生素生物合成途径。对重组表达蛋白的功能分析表明，BtrL和BtrP均负责新胺的核糖化，核糖供体为5-磷酸核糖-L-二磷酸。进一步的详细分析表明，这一过程是通过两个离散的步骤进行的：BtrL首先催化新胺的磷酸核糖离子生成5“-磷酸核糖菌素，然后由BtrP催化去磷酸化生成核糖霉素。据我们所知，这是首次报道氨基糖苷类生物合成基因簇中的糖基转移酶的功能特征。(C)2007 Elsevier Ltd.保留所有权利。
Using a comparative genetics approach, one or more of the BtrA, BtrL, BtrP, and BtrV proteins encoded in the butirosin biosynthetic gene cluster (btr) from Bacillus circulans SANK72073 were identified as being responsible for an O-ribosylation process leading to the formation of ribostamycin, a key intermediate in this, and related antibiotic biosynthetic pathways. Functional analysis of the recombinantly expressed proteins revealed that both BtrL and BtrP were responsible for the ribosylation of neamine, using 5-phosphoribosyl-l-diphosphate (PRPP) as the ribosyl donor. Further detailed analysis indicated that this process occurs via two discrete steps: with BtrL first catalyzing the phosphoribosylaion of neamine to form 5"-phosphoribostamycin, followed by a BtrP-catalyzed dephosphorylation to generate ribostamycin. To the best of our knowledge, this is the first time that the functional characterization of a glycosyltransferase from an aminoglycoside biosynthetic gene cluster has been reported. (c) 2007 Elsevier Ltd. All rights reserved.