Program in Biomolecular Science and Engineering, University of California, Santa Barbara, CA, USA.
Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA, USA.
Nat Commun. 2024 Sep 12;15(1):7980. doi: 10.1038/s41467-024-52362-x.
Modern life is essentially homochiral, containing D-sugars in nucleic acid backbones and L-amino acids in proteins. Since coded proteins are theorized to have developed from a prebiotic RNA World, the homochirality of L-amino acids observed in all known life presumably resulted from chiral transfer from a homochiral D-RNA World. This transfer would have been mediated by aminoacyl-RNAs defining the genetic code. Previous work on aminoacyl transfer using tRNA mimics has suggested that aminoacylation using D-RNA may be inherently biased toward reactivity with L-amino acids, implying a deterministic path from a D-RNA World to L-proteins. Using a model system of self-aminoacylating D-ribozymes and epimerizable activated amino acid analogs, we test the chiral selectivity of 15 ribozymes derived from an exhaustive search of sequence space. All of the ribozymes exhibit detectable selectivity, and a substantial fraction react preferentially to produce the D-enantiomer of the product. Furthermore, chiral preference is conserved within sequence families. These results are consistent with the transfer of chiral information from RNA to proteins but do not support an intrinsic bias of D-RNA for L-amino acids. Different aminoacylation structures result in different directions of chiral selectivity, such that L-proteins need not emerge from a D-RNA World.
现代生活本质上是手性的,包含核酸骨架中的 D-糖和蛋白质中的 L-氨基酸。由于编码蛋白质被理论化为从前生物 RNA 世界发展而来,因此在所有已知生命中观察到的 L-氨基酸的手性可能是由于手性从手性 D-RNA 世界转移而来。这种转移将由定义遗传密码的氨酰-RNA 介导。以前使用 tRNA 模拟物进行的氨酰基转移研究表明,使用 D-RNA 的氨酰化可能固有地偏向于与 L-氨基酸反应,这意味着从 D-RNA 世界到 L-蛋白质存在确定的途径。使用自我氨酰化 D-核酶和可外消旋的活化氨基酸类似物的模型系统,我们测试了来自序列空间穷尽搜索的 15 个核酶的手性选择性。所有核酶都表现出可检测的选择性,并且相当一部分反应优先产生产物的 D-对映体。此外,手性偏好在序列家族内得到保留。这些结果与从 RNA 向蛋白质传递手性信息一致,但不支持 D-RNA 对 L-氨基酸的固有偏见。不同的氨酰化结构导致不同的手性选择性方向,因此 L-蛋白质不一定来自 D-RNA 世界。