NASA Astrobiology Biogeocatalysis Research Center, Department of Chemistry and Biochemistry, Montana State University, Bozeman, Montana 59717, USA.
J Comput Chem. 2011 Nov 30;32(15):3194-206. doi: 10.1002/jcc.21901. Epub 2011 Aug 26.
The biosynthesis of the active site of the [FeFe]-hydrogenases (H-cluster) remains a tantalizing puzzle due to its unprecedented and complex ligand environment. It contains a [2Fe] cluster (2Fe) bearing cyanide and carbon monoxide ligands attached to low-valence Fe ions and an abiological dithiolate ligand (SCH(2)XCH(2)S)(2-) that bridges the two iron centers. Various experimentally testable hypotheses have already been put forward regarding the precursor molecule and the biosynthetic mechanism that leads to the formation of the dithiolate ligand. In this work, we report a density functional theory-based theoretical evaluation of these hypotheses. We find preference for a mechanistically simple and energetically favorable pathway that includes known radical-SAM (S-adenosylmethionine) catalyzed reactions. We modeled this pathway using a long alkyl chain precursor molecule that leads to the formation of pronanadithiolate (X = CH(2)). However, the same pathway can be readily adopted for the biosynthesis of the dithiomethylamine (X = NH) or the dithiomethylether (X = O) analog, provided that the proper precursor molecule is available.
由于其前所未有的复杂配体环境，[FeFe]-氢化酶（H 簇）活性部位的生物合成仍然是一个诱人的难题。它包含一个带有氰化物和一氧化碳配体的[2Fe]簇(2Fe)，这些配体附着在低价态的 Fe 离子上，还有一个非生物的二硫代羧酸配体(SCH(2)XCH(2)S)(2-)，它桥接两个铁中心。关于前体分子和导致二硫代羧酸配体形成的生物合成机制，已经提出了各种可通过实验检验的假设。在这项工作中，我们报告了基于密度泛函理论的这些假设的理论评估。我们发现，一种机制简单且能量有利的途径具有优势，该途径包括已知的自由基-SAM（S-腺苷甲硫氨酸）催化反应。我们使用长烷基链前体分子模拟了这条途径，该前体分子导致 pronanadithiolate（X = CH(2)）的形成。然而，如果有合适的前体分子，同样的途径可以很容易地被用于生物合成二硫甲基胺（X = NH）或二硫甲基醚（X = O）类似物。
