Nucleotidylation of unsaturated carbasugar in validamycin biosynthesis.
Nucleotidylation of unsaturated carbasugar in validamycin biosynthesis.
复制标题
井冈霉素生物合成中不饱和卡巴糖的核苷酸化。
DOI：
10.1039/c0ob00475h
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发表时间：
2011-01-21
影响因子：
3.2
通讯作者：
Mahmud T
中科院分区：
文献类型：
--
作者：
Yang J;Xu H;Zhang Y;Bai L;Deng Z;Mahmud T
井冈霉素A是微生物来源的C（7）N-氨基环醇家族的天然产物，被广泛用作作物保护剂和抗糖尿病药物伏格列波糖的前体。它的生物合成基因簇已被确定在几个吸水链霉菌菌株，并在簇内的一些基因进行了功能分析。在这些基因中，通过失活研究发现，编码糖核苷酸转移酶的valB对井冈霉素的生物合成至关重要，但其作用尚不清楚。为了表征ValB在井冈霉素生物合成中的作用，合成了四种卡巴糖磷酸类似物并作为ValB的底物进行测试。结果表明，ValB有效地催化井冈霉烯醇1-磷酸转化为其核苷酸二磷酸衍生物，而其他不饱和碳糖磷酸被发现不是优选的底物。ValB需要Mg（2+）、Mn（2+）或Co（2+）以获得其最佳活性，并且比基于嘧啶的NTP（CTP、dTTP和UTP）更有效地使用基于嘌呤的核苷酸三磷酸（ATP和GTP）作为核苷酸供体。ValB代表参与天然产物生物合成的不饱和碳糖核苷酸转移酶的第一个成员。它的表征不仅扩大了我们对氨基环醇衍生的天然产物生物合成的理解，而且还可能促进碳水化合物模拟物的化学酶促合成的新工具的开发。
Validamycin A is a member of microbial-derived C(7)N-aminocyclitol family of natural products that is widely used as crop protectant and the precursor of the antidiabetic drug voglibose. Its biosynthetic gene clusters have been identified in several Streptomyces hygroscopicus strains, and a number of genes within the clusters have been functionally analyzed. Of these genes, valB, which encodes a sugar nucleotidyltransferase, was found through inactivation study to be essential for validamycin biosynthesis, but its role was unclear. To characterize the role of ValB in validamycin biosynthesis, four carbasugar phosphate analogues were synthesized and tested as substrate for ValB. The results showed that ValB efficiently catalyzes the conversion of valienol 1-phosphate to its nucleotidyl diphosphate derivatives, whereas other unsaturated carbasugar phosphates were found to be not the preferred substrate. ValB requires Mg(2+), Mn(2+), or Co(2+) for its optimal activity and uses the purine-based nucleotidyltriphosphates (ATP and GTP) more efficiently than the pyrimidine-based NTPs (CTP, dTTP, and UTP) as nucleotidyl donor. ValB represents the first member of unsaturated carbasugar nucleotidyltransferases involved in natural products biosynthesis. Its characterization not only expands our understanding of aminocyclitol-derived natural products biosynthesis, but may also facilitate the development of new tools for chemoenzymatic synthesis of carbohydrate mimetics.
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影响因子：
4.8
作者：
Bejar, Clarisa Maria;Jin, Xiangshu;Preiss, Jack
通讯作者：
Preiss, Jack
影响因子：
15
作者：
Dong, HJ;Mahmud, T;Floss, HG
通讯作者：
Floss, HG
DOI：
10.1073/pnas.0337542100
发表时间：
2003-02-18
影响因子：
11.1
作者：
Gust, B;Challis, GL;Chater, KF
通讯作者：
Chater, KF
影响因子：
6.6
作者：
Mahmud, T;Lee, S;Floss, HG
通讯作者：
Floss, HG
ValC 是一种新型 C7-环醇激酶，参与抗真菌剂井冈霉素 A 的生物合成。
影响因子：
3.2
作者：
Minagawa, Kazuyuki;Zhang, Yirong;Mahmud, Taifo
通讯作者：
Mahmud, Taifo