Salvage of the 5-deoxyribose byproduct of radical SAM enzymes.

Salvage of the 5-deoxyribose byproduct of radical SAM enzymes.
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DOI:
10.1038/s41467-018-05589-4
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发表时间:
2018-08-06
影响因子:
16.6
通讯作者:
Hanson AD
Hanson AD
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Beaudoin GAW;Li Q;Folz J;Fiehn O;Goodsell JL;Angerhofer A;Bruner SD;Hanson AD

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5-脱氧核糖由5′-脱氧腺苷形成,5 ′-脱氧腺苷是自由基S-腺苷甲硫氨酸(SAM)酶的毒性副产物。5-脱氧核糖的降解命运未知。在这里,我们定义了5-脱氧核糖在细菌中的补救途径,包括磷酸化,异构化和羟醛裂解步骤。细菌基因组的分析揭示了广泛的,未分配的三个基因簇指定一个假定的激酶,异构酶,和糖磷酸醛缩酶。我们表明,由苏云金芽孢杆菌集群编码的酶,在体外共同作用,将5-脱氧核糖依次转化为5-脱氧核糖1-磷酸,5-脱氧核酮糖1-磷酸,和二羟丙酮磷酸加乙醛。删除异构酶会降低5-脱氧核酮糖1-磷酸池的大小,删除异构酶或醛缩酶会增加对5-脱氧核糖的敏感性。醛缩酶的底物偏好在家族成员中是独特的,X射线结构揭示了一种不寻常的锰依赖酶。这项工作定义了5-脱氧核糖(一种几乎通用的代谢物)的补救途径。5-脱氧核糖由5′-脱氧腺苷形成,5 ′-脱氧腺苷是自由基S-腺苷甲硫氨酸酶的毒性副产物。在这里,作者确定和生化特性的5-脱氧核糖,由三种酶组成的细菌补救途径,并解决了关键的醛缩酶的晶体结构。
5-Deoxyribose is formed from 5′-deoxyadenosine, a toxic byproduct of radical S-adenosylmethionine (SAM) enzymes. The degradative fate of 5-deoxyribose is unknown. Here, we define a salvage pathway for 5-deoxyribose in bacteria, consisting of phosphorylation, isomerization, and aldol cleavage steps. Analysis of bacterial genomes uncovers widespread, unassigned three-gene clusters specifying a putative kinase, isomerase, and sugar phosphate aldolase. We show that the enzymes encoded by the Bacillus thuringiensis cluster, acting together in vitro, convert 5-deoxyribose successively to 5-deoxyribose 1-phosphate, 5-deoxyribulose 1-phosphate, and dihydroxyacetone phosphate plus acetaldehyde. Deleting the isomerase decreases the 5-deoxyribulose 1-phosphate pool size, and deleting either the isomerase or the aldolase increases susceptibility to 5-deoxyribose. The substrate preference of the aldolase is unique among family members, and the X-ray structure reveals an unusual manganese-dependent enzyme. This work defines a salvage pathway for 5-deoxyribose, a near-universal metabolite. 5-Deoxyribose is formed from 5′-deoxyadenosine, a toxic byproduct of radical S-adenosylmethionine enzymes. Here, the authors identify and biochemically characterize a bacterial salvage pathway for 5-deoxyribose, consisting of three enzymes, and solve the crystal structure of the key aldolase.
DOI: 10.1007/bf00325702
发表时间: 1987-12-01
期刊: MOLECULAR AND GENERAL GENETICS
影响因子: --
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