Abstract

Sulfur is an essential element for a variety of cellular constituents in all living organisms and adds considerable functionality to a wide range of biomolecules. The pathways for incorporating sulfur into central metabolites of the cell such as cysteine, methionine, cystathionine, and homocysteine have long been established. Furthermore, the importance of persulfide intermediates during the biosynthesis of thionucleotide-containing tRNAs, iron-sulfur clusters, thiamin diphosphate, and the molybdenum cofactor are well known. This review briefly surveys these topics while emphasizing more recent aspects of sulfur metabolism that involve unconventional biosynthetic pathways. Sacrificial sulfur transfers from protein cysteinyl side chains to precursors of thiamin and the nickel-pincer nucleotide (NPN) cofactor are described. Newer aspects of synthesis for lipoic acid, biotin, and other compounds are summarized, focusing on the requisite iron-sulfur cluster destruction. Sulfur transfers by using a noncore sulfide ligand bound to a [4Fe-4S] cluster are highlighted for generating certain thioamides and for alternative biosynthetic pathways of thionucleotides and the NPN cofactor. Thioamide formation by activating an amide oxygen atom via phosphorylation also is illustrated. The discussion of these topics stresses the chemical reaction mechanisms of the transformations and generally avoids comments on the gene/protein nomenclature or the sources of the enzymes. This work sets the stage for future efforts to decipher the diverse mechanisms of sulfur incorporation into biological molecules.

摘要

硫是所有生物体中多种细胞成分的必需元素，并为多种生物分子增加了相当多的功能。将硫掺入细胞中心代谢物（如半胱氨酸、蛋氨酸、胱硫醚和同型半胱氨酸）的途径早已建立。此外，过硫化物中间体在含硫核苷酸的 tRNA、铁硫簇、二磷酸硫胺素和钼辅因子的生物合成过程中的重要性是众所周知的。本综述简要调查了这些主题，同时强调了涉及非常规生物合成途径的硫代谢的最新方面。描述了从蛋白质半胱氨酰侧链到硫胺素前体和镍钳核苷酸 (NPN) 辅因子的牺牲硫转移。总结了硫辛酸、生物素和其他化合物合成的新方面，重点是必要的铁硫簇破坏。通过使用与 [4Fe-4S] 簇结合的非核心硫化物配体进行的硫转移被强调用于生成某些硫代酰胺以及硫代核苷酸和 NPN 辅因子的替代生物合成途径。还说明了通过磷酸化激活酰胺氧原子形成硫代酰胺。这些主题的讨论强调转化的化学反应机制，通常避免对基因/蛋白质命名法或酶来源的评论。这项工作为未来破译硫掺入生物分子的多种机制奠定了基础。