Li Hong, Xu Huimin, Graham David E, White Robert H
Department of Biochemistry (0308), Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9785-90. doi: 10.1073/pnas.1733391100. Epub 2003 Aug 8.
Proteins in the ATP-grasp superfamily of amide bond-forming ligases have evolved to function in a number of unrelated biosynthetic pathways. Previously identified homologs encoding glutathione synthetase, d-alanine:d-alanine ligase and the bacterial ribosomal protein S6:glutamate ligase have been vertically inherited within certain organismal lineages. Although members of this specificity-diverse superfamily share a common reaction mechanism, the nonoverlapping set of amino acid and peptide substrates recognized by each family provided few clues as to their evolutionary history. Two members of this family have been identified in the hyperthermophilic marine archaeon Methanococcus jannaschii and shown to catalyze the final reactions in two coenzyme biosynthetic pathways. The MJ0620 (mptN) locus encodes a tetrahydromethanopterin:alpha-l-glutamate ligase that forms tetrahydrosarcinapterin, a single carbon-carrying coenzyme. The MJ1001 (cofF) locus encodes a gamma-F420-2:alpha-l-glutamate ligase, which caps the gamma-glutamyl tail of the hydride carrier coenzyme F420. These two genes share a common ancestor with the ribosomal protein S6:glutamate ligase and a putative alpha-aminoadipate ligase, defining the first group of ATP-grasp enzymes with a shared amino acid substrate specificity. As in glutathione biosynthesis, two unrelated amino acid ligases catalyze sequential reactions in coenzyme F420 polyglutamate formation: a gamma-glutamyl ligase adds 1-3 l-glutamate residues and the ATP-grasp-type ligase described here caps the chain with a single alpha-linked l-glutamate residue. The analogous pathways for glutathione, F420, folate, and murein peptide biosyntheses illustrate convergent evolution of nonribosomal peptide biosynthesis through the recruitment of single-step amino acid ligases.
ATP抓取超家族中负责形成酰胺键的连接酶所包含的蛋白质，已经进化到能在许多不相关的生物合成途径中发挥作用。先前鉴定出的编码谷胱甘肽合成酶、D-丙氨酸：D-丙氨酸连接酶和细菌核糖体蛋白S6：谷氨酸连接酶的同源物，在某些生物谱系中是垂直遗传的。尽管这个特异性多样的超家族成员共享一种共同的反应机制，但每个家族所识别的不重叠的氨基酸和肽底物集，几乎没有提供关于它们进化历史的线索。在嗜热海洋古菌詹氏甲烷球菌中鉴定出了该家族的两个成员，并表明它们催化两种辅酶生物合成途径中的最终反应。MJ0620（mptN）基因座编码一种四氢甲烷蝶呤：α-L-谷氨酸连接酶，该酶形成四氢肌苷蝶呤，一种单碳携带辅酶。MJ1001（cofF）基因座编码一种γ-F420-2：α-L-谷氨酸连接酶，该酶封闭氢化物载体辅酶F420的γ-谷氨酰尾部。这两个基因与核糖体蛋白S6：谷氨酸连接酶和一种假定的α-氨基己二酸连接酶有共同的祖先，定义了第一组具有共享氨基酸底物特异性的ATP抓取酶。与谷胱甘肽生物合成一样，两种不相关的氨基酸连接酶催化辅酶F420聚谷氨酸形成过程中的连续反应：一种γ-谷氨酰连接酶添加1-3个L-谷氨酸残基，此处描述的ATP抓取型连接酶用一个α-连接的L-谷氨酸残基封闭该链。谷胱甘肽、F420、叶酸和胞壁肽生物合成的类似途径，说明了通过招募单步氨基酸连接酶实现非核糖体肽生物合成的趋同进化。
