Horticultural Sciences Department, University of Florida, Gainesville, FL, 32611, USA.
Department of Chemistry, University of Florida, Gainesville, FL, 32611, USA.
Nat Commun. 2018 Aug 6;9(1):3105. doi: 10.1038/s41467-018-05589-4.
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-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)酶的有毒副产物。5-脱氧核糖的降解命运尚不清楚。在这里,我们在细菌中定义了 5-脱氧核糖的补救途径,包括磷酸化、异构化和醛缩裂解步骤。对细菌基因组的分析揭示了广泛存在的、未分配的三基因簇,指定了一个假定的激酶、异构酶和糖磷酸醛缩酶。我们表明,苏云金芽孢杆菌簇中编码的酶在体外一起作用,将 5-脱氧核糖依次转化为 5-脱氧核糖 1-磷酸、5-脱氧核糖 1-磷酸、二羟丙酮磷酸和乙醛。删除异构酶会减少 5-脱氧核糖 1-磷酸池的大小,并且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性酶。这项工作定义了 5-脱氧核糖的补救途径,5-脱氧核糖是一种近乎普遍存在的代谢物。