Synthesis at the Interface of Chemistry and Biology

化学与生物学交叉点的合成

• 批准号: 10406629
• 负责人: PETER G SCHULTZ
• 金额: $ 47.94万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10406629
• 关键词: Amino Acids; Back; Bacteria; Bacterial DNA; Biology; Cell Wall; Chemistry; DNA; Evolution; Generations; Genes; Genetic Code; Genome; Life; Metabolic; Mitochondria; Organism; RNA; Ribonucleotides; System; endosymbiont; protein folding; synthetic biology; tool

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.

项目总结/摘要 该提案探讨了合成生物学的三个主要方面-所有相关主题下， 生命的进化：通过创造具有扩展的生物体来展望进化 遗传密码，并通过探索线粒体的进化来回顾进化， 定义的“合成”内共生体系统，并通过探索一种可能的机制， 通过细菌的产生和表征从RNA到DNA世界的过渡 嵌合DNA-RNA基因组。具体地说，我们将在基因组中编码D-氨基酸。 细菌，并创建和应用遗传编码的工具来研究蛋白质折叠/解折叠上的一个 我们将开始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，以及探索那些因素， 有助于该嵌合系统的稳定性;并创建双正交复制系统 并利用它来探索这些因素，使大量的 核糖核苷酸转化为细菌DNA。