Synthesis at the Interface of Chemistry and Biology

项目摘要/摘要 这项提案探讨了合成生物学的三个主要方面-所有这些都在相关的主题下 生命的进化：通过创造具有扩展的有机体来展望进化 遗传密码，以及通过探索井中线粒体的进化来回顾进化- 定义了“合成的”内共生菌系统，并通过探索一种可能的机制 通过细菌的产生和特征从RNA世界过渡到DNA世界 有嵌合的DNA-RNA基因组。具体地说，我们将在基因上编码D-氨基酸 细菌，并创建和应用一种遗传编码工具来研究蛋白质在 亚微秒的时间尺度；我们将开始通过以下方式最小化我们的细菌内共生体基因组 删除代谢和细胞壁生物合成基因，以及探索这些因素 有助于该嵌合系统的稳定；并创建双正交复制系统 并用它来探索那些允许大量 将核糖核苷酸转化为细菌DNA。

Project Summary/Abstract This proposal explores three major aspects of synthetic biology- all under the related theme of the evolution of life: a look forward into evolution by creating organisms with an expanded genetic code, and a look back into evolution by exploring the evolution of mitochondria in a well- defined “synthetic” endosymbiont system, and by exploring one possible mechanism for the transition from the RNA to DNA world through the generation and characterization of bacteria with chimeric DNA-RNA genomes. Specifically, we will genetically encode D-amino acids in bacteria and create and apply a genetically encoded tool to study protein folding/unfolding on a sub-microsecond timescale; we will begin to minimize our bacterial endosymbiont genome by deleting metabolic and cell wall biosynthetic genes, as well as exploring those factors that contribute to the stability of this chimeric system; and create a biorthogonal replication system and use it to explore those factors that allow the incorporation of large numbers of ribonucleotides into bacterial DNA.