Bertelsen Andreas B, Ehrmann Anja K, Bayer Carolyn, Batth Tanveer S, Olsen Jesper V, Nørholm Morten H H
The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby 2800, Denmark.
The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen N 2200, Denmark.
ACS Synth Biol. 2025 Jan 17;14(1):161-170. doi: 10.1021/acssynbio.4c00533. Epub 2024 Dec 19.
Genetic functions have evolved over long timescales and can be encoded by multiple genes dispersed in different locations in genomes, and although contemporary molecular biology enables control over single genes, more complex genetic functions remain challenging. Here, we study the restructuring and mobilization of a complex genetic function encoded by 10 genes, originally expressed from four operons and two loci on the genome. We observe subtle phenotypic differences and reduced fitness when expressed from episomal DNA and demonstrate that mutations in the transcriptional machinery are necessary for successful implementation in different bacteria. The work provides new approaches for advanced genome editing and constitutes a first step toward modularization and genome-level engineering of complex genetic functions.
遗传功能在很长的时间尺度上不断进化，可由分散在基因组不同位置的多个基因编码，尽管当代分子生物学能够控制单个基因，但更复杂的遗传功能仍然具有挑战性。在这里，我们研究了由10个基因编码的复杂遗传功能的重组和动员，这些基因最初由基因组上的四个操纵子和两个位点表达。我们观察到从游离DNA表达时存在细微的表型差异和适应性降低，并证明转录机制中的突变是在不同细菌中成功实现的必要条件。这项工作为先进的基因组编辑提供了新方法，并朝着复杂遗传功能的模块化和基因组水平工程迈出了第一步。
