Integrated translation and metabolism in a partially self-synthesizing biochemical network

• 成果类型: Article
• 署名作者: Giaveri, Simone; Bohra, Nitin; Diehl, Christoph; Yang, Hao Yuan; Ballinger, Martine; Paczia, Nicole; Glatter, Timo; Erb, Tobias J.
• 署名单位: Max Planck Society; Max Planck Society; Max Planck Society
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11814
• DOI: 10.1126/science.adn3856
• 发表日期: 2024-07-12
• 页码: 174-178
• 关键词: pathway; Fixation

摘要

One of the hallmarks of living organisms is their capacity for self-organization and regeneration, which requires a tight integration of metabolic and genetic networks. We sought to construct a linked metabolic and genetic network in vitro that shows such lifelike behavior outside of a cellular context and generates its own building blocks from nonliving matter. We integrated the metabolism of the crotonyl-CoA/ethyl-malonyl-CoA/hydroxybutyryl-CoA cycle with cell-free protein synthesis using recombinant elements. Our network produces the amino acid glycine from CO2 and incorporates it into target proteins following DNA-encoded instructions. By orchestrating similar to 50 enzymes we established a basic cell-free operating system in which genetically encoded inputs into a metabolic network are programmed to activate feedback loops allowing for self-integration and (partial) self-regeneration of the complete system.