A bifunctional salvage pathway for two distinct S-adenosylmethionine by-products that is widespread in bacteria, including pathogenic Escherichia coli
A bifunctional salvage pathway for two distinct S-adenosylmethionine by-products that is widespread in bacteria, including pathogenic Escherichia coli
复制标题
DOI：
10.1111/mmi.14459
复制
发表时间：
2020-02-20
影响因子：
3.6
通讯作者：
Tabita, Fred R.
中科院分区：
文献类型：
--
作者：
North, Justin A.;Wildenthal, John A.;Tabita, Fred R.
S-腺苷甲硫氨酸（SAM）是蛋白质和核苷酸甲基化、次级代谢产物合成和自由基介导的许多重要酶促反应的必需共底物。自由基SAM酶产生5 MODIFIER LETTER PRIME-脱氧腺苷，而SAM依赖性多胺、神经递质和群体感应化合物合成酶产生5 MODIFIER LETTER PRIME-甲硫基腺苷作为副产物。两者都是抑制性的，必须由所有细胞解决。本工作建立了一个双功能的氧非依赖性补救途径5 MODIFIER LETTER PRIME-脱氧腺苷和5 MODIFIER LETTER PRIME-甲硫基腺苷在红杜鹃和肠外致病性大肠杆菌。该途径的同源基因广泛存在于细菌中，特别是几个家族中的致病菌株。磷酸化酶（红色红球菌）或单独的核苷和激酶（大肠杆菌），随后是异构酶和醛缩酶，依次起作用以在需氧和厌氧生长期间将这两种浪费和抑制性化合物挽救为腺嘌呤、磷酸二羟丙酮和乙醛或（2-甲硫基）乙醛。两种SAM副产物在有氧和厌氧生长条件下以相同的亲和力代谢，表明双重目的补救途径在许多环境中起着核心作用，特别是在感染期间的人体。我们新发现的双功能氧非依赖性途径，广泛存在于细菌中，挽救了SAM依赖性酶的至少两种副产物，用于碳和硫的挽救，有助于细胞生长。
S-adenosyl-l-methionine (SAM) is a necessary cosubstrate for numerous essential enzymatic reactions including protein and nucleotide methylations, secondary metabolite synthesis and radical-mediated processes. Radical SAM enzymes produce 5MODIFIER LETTER PRIME-deoxyadenosine, and SAM-dependent enzymes for polyamine, neurotransmitter and quorum sensing compound synthesis produce 5MODIFIER LETTER PRIME-methylthioadenosine as by-products. Both are inhibitory and must be addressed by all cells. This work establishes a bifunctional oxygen-independent salvage pathway for 5MODIFIER LETTER PRIME-deoxyadenosine and 5MODIFIER LETTER PRIME-methylthioadenosine in both Rhodospirillum rubrum and Extraintestinal Pathogenic Escherichia coli. Homologous genes for this pathway are widespread in bacteria, notably pathogenic strains within several families. A phosphorylase (Rhodospirillum rubrum) or separate nucleoside and kinase (Escherichia coli) followed by an isomerase and aldolase sequentially function to salvage these two wasteful and inhibitory compounds into adenine, dihydroxyacetone phosphate and acetaldehyde or (2-methylthio)acetaldehyde during both aerobic and anaerobic growth. Both SAM by-products are metabolized with equal affinity during aerobic and anaerobic growth conditions, suggesting that the dual-purpose salvage pathway plays a central role in numerous environments, notably the human body during infection. Our newly discovered bifunctional oxygen-independent pathway, widespread in bacteria, salvages at least two by-products of SAM-dependent enzymes for carbon and sulfur salvage, contributing to cell growth.