National Key Laboratory of Crop Genetic Improvement, Center for Bioinformatics, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
J Biomol Struct Dyn. 2012;30(5):542-5. doi: 10.1080/07391102.2012.687520. Epub 2012 Jun 25.
Cysteine (Cys) has unique chemical properties of catalysis, metal chelation, and protein stabilization. While Cys biosynthesis is assumed to be very ancient, the actual time of origin of these metabolic pathways remains unknown. Here, we use the molecular clocks of protein folds and fold superfamilies to time the origin of Cys biosynthesis. We find that the tRNA-dependent biosynthetic pathway appeared ~3.5 billion years ago while the tRNA-independent counterpart emerged ~500 million years later. A deep analysis of the origins of Cys biosynthesis in the context of emerging biochemistry uncovers some intriguing features of the planetary environment of early Earth. Results suggest that iron-sulfur (Fe-S) proteins that use cysteinyl sulfur to bind iron atoms were not the first to arise in evolution. Instead, their origin coincides with the appearance of the first Cys biosynthetic pathway. It is therefore likely that Cys did not play an important role in the make up of primordial protein molecules and that Fe-S clusters were not part of active sites at the beginning of biological history.
半胱氨酸（Cys）具有催化、金属螯合和蛋白质稳定等独特的化学性质。虽然 Cys 的生物合成被认为非常古老，但这些代谢途径的实际起源时间仍不清楚。在这里，我们使用蛋白质折叠和折叠超家族的分子钟来确定 Cys 生物合成的起源时间。我们发现，依赖 tRNA 的生物合成途径出现在约 35 亿年前，而不依赖 tRNA 的对应途径则出现在约 5 亿年后。在新兴生物化学的背景下对半胱氨酸生物合成起源的深入分析揭示了早期地球行星环境的一些有趣特征。结果表明，使用半胱氨酸硫基结合铁原子的铁硫（Fe-S）蛋白并不是进化中最早出现的。相反，它们的起源与第一个 Cys 生物合成途径的出现相吻合。因此，Cys 可能在原始蛋白质分子的组成中没有发挥重要作用，而且 Fe-S 簇在生物历史的早期也不是活性位点的一部分。
