François-Xavier Lehr, Bruno Pavletić, Timo Glatter, Thomas Heimerl, Ralf Moeller, Henrike Niederholtmeyer
{"title":"在模拟微重力条件下,在无细胞反应中产生的噬菌体 T7 的组装能力增强。","authors":"François-Xavier Lehr, Bruno Pavletić, Timo Glatter, Thomas Heimerl, Ralf Moeller, Henrike Niederholtmeyer","doi":"10.1038/s41526-024-00378-4","DOIUrl":null,"url":null,"abstract":"<p><p>On-demand biomanufacturing has the potential to improve healthcare and self-sufficiency during space missions. Cell-free transcription and translation reactions combined with DNA blueprints can produce promising therapeutics like bacteriophages and virus-like particles. However, how space conditions affect the synthesis and self-assembly of such complex multi-protein structures is unknown. Here, we characterize the cell-free production of infectious bacteriophage T7 virions under simulated microgravity. Rotation in a 2D-clinostat increased the number of infectious particles compared to static controls. Quantitative analyses by mass spectrometry, immuno-dot-blot and real-time PCR showed no significant differences in protein and DNA contents, suggesting enhanced self-assembly of T7 phages in simulated microgravity. While the effects of genuine space conditions on the cell-free synthesis and assembly of bacteriophages remain to be investigated, our findings support the vision of a cell-free synthesis-enabled \"astropharmacy\".</p>","PeriodicalId":54263,"journal":{"name":"npj Microgravity","volume":null,"pages":null},"PeriodicalIF":4.4000,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10943216/pdf/","citationCount":"0","resultStr":"{\"title\":\"Enhanced assembly of bacteriophage T7 produced in cell-free reactions under simulated microgravity.\",\"authors\":\"François-Xavier Lehr, Bruno Pavletić, Timo Glatter, Thomas Heimerl, Ralf Moeller, Henrike Niederholtmeyer\",\"doi\":\"10.1038/s41526-024-00378-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>On-demand biomanufacturing has the potential to improve healthcare and self-sufficiency during space missions. Cell-free transcription and translation reactions combined with DNA blueprints can produce promising therapeutics like bacteriophages and virus-like particles. However, how space conditions affect the synthesis and self-assembly of such complex multi-protein structures is unknown. Here, we characterize the cell-free production of infectious bacteriophage T7 virions under simulated microgravity. Rotation in a 2D-clinostat increased the number of infectious particles compared to static controls. Quantitative analyses by mass spectrometry, immuno-dot-blot and real-time PCR showed no significant differences in protein and DNA contents, suggesting enhanced self-assembly of T7 phages in simulated microgravity. While the effects of genuine space conditions on the cell-free synthesis and assembly of bacteriophages remain to be investigated, our findings support the vision of a cell-free synthesis-enabled \\\"astropharmacy\\\".</p>\",\"PeriodicalId\":54263,\"journal\":{\"name\":\"npj Microgravity\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2024-03-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10943216/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"npj Microgravity\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1038/s41526-024-00378-4\",\"RegionNum\":1,\"RegionCategory\":\"物理与天体物理\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"npj Microgravity","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1038/s41526-024-00378-4","RegionNum":1,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
摘要
按需生物制造有可能改善太空任务中的医疗保健和自给自足。无细胞转录和翻译反应与 DNA 蓝图相结合,可以生产出噬菌体和类病毒颗粒等前景广阔的治疗药物。然而,太空条件如何影响这种复杂的多蛋白结构的合成和自我组装尚不清楚。在这里,我们描述了在模拟微重力条件下无细胞生产传染性噬菌体 T7 病毒的过程。与静态对照组相比,在二维-抑制剂中旋转增加了感染性颗粒的数量。质谱仪、免疫点印迹和实时聚合酶链反应的定量分析显示,蛋白质和DNA含量没有显著差异,这表明在模拟微重力条件下,T7噬菌体的自组装能力增强了。虽然真正的太空条件对无细胞合成和组装噬菌体的影响还有待研究,但我们的研究结果支持了无细胞合成 "天体药剂学 "的愿景。
Enhanced assembly of bacteriophage T7 produced in cell-free reactions under simulated microgravity.
On-demand biomanufacturing has the potential to improve healthcare and self-sufficiency during space missions. Cell-free transcription and translation reactions combined with DNA blueprints can produce promising therapeutics like bacteriophages and virus-like particles. However, how space conditions affect the synthesis and self-assembly of such complex multi-protein structures is unknown. Here, we characterize the cell-free production of infectious bacteriophage T7 virions under simulated microgravity. Rotation in a 2D-clinostat increased the number of infectious particles compared to static controls. Quantitative analyses by mass spectrometry, immuno-dot-blot and real-time PCR showed no significant differences in protein and DNA contents, suggesting enhanced self-assembly of T7 phages in simulated microgravity. While the effects of genuine space conditions on the cell-free synthesis and assembly of bacteriophages remain to be investigated, our findings support the vision of a cell-free synthesis-enabled "astropharmacy".
npj MicrogravityPhysics and Astronomy-Physics and Astronomy (miscellaneous)
CiteScore
7.30
自引率
7.80%
发文量
50
审稿时长
9 weeks
期刊介绍:
A new open access, online-only, multidisciplinary research journal, npj Microgravity is dedicated to publishing the most important scientific advances in the life sciences, physical sciences, and engineering fields that are facilitated by spaceflight and analogue platforms.