PDF(Pubmed)
Abstract：
All organisms utilize S-adenosyl-l-methionine (SAM) as a key co-substrate for the methylation of biological molecules, the synthesis of polyamines, and radical SAM reactions. When these processes occur, 5\'-deoxy-nucleosides are formed as byproducts such as S-adenosyl-l-homocysteine, 5\'-methylthioadenosine (MTA), and 5\'-deoxyadenosine (5dAdo). A prevalent pathway found in bacteria for the metabolism of MTA and 5dAdo is the dihydroxyacetone phosphate (DHAP) shunt, which converts these compounds into dihydroxyacetone phosphate and 2-methylthioacetaldehyde or acetaldehyde, respectively. Previous work in other organisms has shown that the DHAP shunt can enable methionine synthesis from MTA or serve as an MTA and 5dAdo detoxification pathway. Rather, the DHAP shunt in Escherichia coli ATCC 25922, when introduced into E. coli K-12, enables the use of 5dAdo and MTA as a carbon source for growth. When MTA is the substrate, the sulfur component is not significantly recycled back to methionine but rather accumulates as 2-methylthioethanol, which is slowly oxidized non-enzymatically under aerobic conditions. The DHAP shunt in ATCC 25922 is active under oxic and anoxic conditions. Growth using 5-deoxy-d-ribose was observed during aerobic respiration and anaerobic respiration with Trimethylamine N-oxide (TMAO), but not during fermentation or respiration with nitrate. This suggests the DHAP shunt may only be relevant for extraintestinal pathogenic E. coli lineages with the DHAP shunt that inhabit oxic or TMAO-rich extraintestinal environments. This reveals a heretofore overlooked role of the DHAP shunt in carbon and energy metabolism from ubiquitous SAM utilization byproducts and suggests a similar role may occur in other pathogenic and non-pathogenic bacteria with the DHAP shunt.
OBJECTIVE: The acquisition and utilization of organic compounds that serve as growth substrates are essential for Escherichia coli to grow and multiply. Ubiquitous enzymatic reactions involving S-adenosyl-l-methionine as a co-substrate by all organisms result in the formation of the 5\'-deoxy-nucleoside byproducts, 5\'-methylthioadenosine and 5\'-deoxyadenosine. All E. coli possess a conserved nucleosidase that cleaves these 5\'-deoxy-nucleosides into 5-deoxy-pentose sugars for adenine salvage. The DHAP shunt pathway is found in some extraintestinal pathogenic E. coli, but its function in E. coli possessing it has remained unknown. This study reveals that the DHAP shunt enables the utilization of 5\'-deoxy-nucleosides and 5-deoxy-pentose sugars as growth substrates in E. coli strains with the pathway during aerobic respiration and anaerobic respiration with TMAO, but not fermentative growth. This provides an insight into the diversity of sugar compounds accessible by E. coli with the DHAP shunt and suggests that the DHAP shunt is primarily relevant in oxic or TMAO-rich extraintestinal environments.
OBJECTIVE: The acquisition and utilization of organic compounds that serve as growth substrates are essential for Escherichia coli to grow and multiply. Ubiquitous enzymatic reactions involving S-adenosyl-l-methionine as a co-substrate by all organisms result in the formation of the 5\'-deoxy-nucleoside byproducts, 5\'-methylthioadenosine and 5\'-deoxyadenosine. All E. coli possess a conserved nucleosidase that cleaves these 5\'-deoxy-nucleosides into 5-deoxy-pentose sugars for adenine salvage. The DHAP shunt pathway is found in some extraintestinal pathogenic E. coli, but its function in E. coli possessing it has remained unknown. This study reveals that the DHAP shunt enables the utilization of 5\'-deoxy-nucleosides and 5-deoxy-pentose sugars as growth substrates in E. coli strains with the pathway during aerobic respiration and anaerobic respiration with TMAO, but not fermentative growth. This provides an insight into the diversity of sugar compounds accessible by E. coli with the DHAP shunt and suggests that the DHAP shunt is primarily relevant in oxic or TMAO-rich extraintestinal environments.
摘要：
所有生物体利用S-腺苷-1-甲硫氨酸（SAM）作为生物分子甲基化的关键共底物，多胺的合成，和激进的SAM反应。当这些过程发生时，5'-脱氧核苷作为副产物形成，如S-腺苷-1-高半胱氨酸，5'-甲硫腺苷（MTA），和5'-脱氧腺苷(5dAdo)。在细菌中发现的MTA和5dAdo代谢的普遍途径是磷酸二羟丙酮（DHAP）分流，将这些化合物转化为磷酸二羟基丙酮和2-甲硫基乙醛或乙醛，分别。先前在其他生物体中的工作表明，DHAP分流可以使MTA合成甲硫氨酸或充当MTA和5dAdo解毒途径。相反，大肠杆菌ATCC25922中的DHAP分流,当引入大肠杆菌K-12时,能够使用5dAdo和MTA作为生长的碳源。当MTA为底物时,硫成分不会明显循环回蛋氨酸，而是积累为2-甲硫基乙醇，在需氧条件下非酶缓慢氧化。ATCC25922中的DHAP分流器在有氧和缺氧条件下具有活性。在有氧呼吸和三甲胺N-氧化物（TMAO）的无氧呼吸期间，观察到使用5-脱氧-d-核糖的生长，但不是在用硝酸盐发酵或呼吸的过程中。这表明DHAP分流可能仅与在有毒或富含TMAO的肠外环境中栖息的DHAP分流的肠外致病性大肠杆菌谱系有关。这揭示了迄今为止DHAP分流在普遍存在的SAM利用副产物的碳和能量代谢中的作用，并表明在DHAP分流的其他致病性和非致病性细菌中可能会发生类似的作用。
目的：获取和利用用作生长底物的有机化合物对于大肠杆菌的生长和繁殖至关重要。涉及S-腺苷-1-甲硫氨酸作为共底物的所有生物体的普遍酶促反应导致5'-脱氧核苷副产物的形成。5'-甲硫腺苷和5'-脱氧腺苷。所有大肠杆菌都具有保守的核苷酶，可将这些5'-脱氧核苷裂解成5-脱氧戊糖以进行腺嘌呤补救。DHAP分流途径在一些肠外致病性大肠杆菌中发现，但是它在大肠杆菌中的功能仍然未知。这项研究表明，DHAP分流器能够利用5'-脱氧核苷和5-脱氧戊糖作为大肠杆菌菌株的生长底物，在有氧呼吸和无氧呼吸过程中使用TMAO，但不是发酵生长。这提供了对具有DHAP分流的大肠杆菌可获得的糖化合物的多样性的见解，并表明DHAP分流主要与富含氧或TMAO的肠外环境有关。
目的：获取和利用用作生长底物的有机化合物对于大肠杆菌的生长和繁殖至关重要。涉及S-腺苷-1-甲硫氨酸作为共底物的所有生物体的普遍酶促反应导致5'-脱氧核苷副产物的形成。5'-甲硫腺苷和5'-脱氧腺苷。所有大肠杆菌都具有保守的核苷酶，可将这些5'-脱氧核苷裂解成5-脱氧戊糖以进行腺嘌呤补救。DHAP分流途径在一些肠外致病性大肠杆菌中发现，但是它在大肠杆菌中的功能仍然未知。这项研究表明，DHAP分流器能够利用5'-脱氧核苷和5-脱氧戊糖作为大肠杆菌菌株的生长底物，在有氧呼吸和无氧呼吸过程中使用TMAO，但不是发酵生长。这提供了对具有DHAP分流的大肠杆菌可获得的糖化合物的多样性的见解，并表明DHAP分流主要与富含氧或TMAO的肠外环境有关。
