ビール酵母の注文(Order for brewer`s yeast)

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細胞内タンパク質産生のためのすべてのt-RNA遺伝子を結合した人工染色体 An artificial chromosome combines all t-RNA genes for cellular protein production

2023-11-10 マックス・プランク研究所

◆マンチェスター生物工学研究所主導の研究で、マックス・プランク地球微生物研究所のチームが合成生物学を用いて、醸酵酵母に自然に存在しないtRNAネオクロモソームを成功裏に生成。
◆これは国際的な合成酵母ゲノムプロジェクト(Sc2.0)の一環で、ベーカーズイーストの16染色体を合成し、完全に合成された細胞を構築する目標を達成。合成染色体は株の強度向上や細胞増殖促進に寄与し、新染色体は自然にない情報の格納や新しい株の創出に可能性を提供。
◆国際チームは6.5本の染色体を組み合わせて機能する細胞も成功させ、Sc2.0プロジェクトは異分野の専門家が協力して進行中。これにより基礎研究の進展と将来のバイオテクノロジーへの応用が期待されています。

<関連情報>

酵母におけるtRNAネオクロモソームの設計、構築、および機能的特性評価 Design, construction, and functional characterization of a tRNA neochromosome in yeast

Daniel Schindler,Roy S.K. Walker,Shuangying Jiang,Aaron N. Brooks,Yun Wang,Carolin A. Müller,Charlotte Cockram,Yisha Luo,Alicia García,Daniel Schraivogel,Julien Mozziconacci,Noah Pena,Mahdi Assari,María del Carmen Sánchez Olmos,Yu Zhao,Alba Ballerini,Benjamin A. Blount,Jitong Cai,Lois Ogunlana,Wei Liu,Katarina Jönsson,Dariusz Abramczyk,Eva Garcia-Ruiz,Tomasz W. Turowski,Reem Swidah,Tom Ellis,Tao Pan,Francisco Antequera,Yue Shen,Conrad A. Nieduszynski,Romain Koszul,Junbiao Dai,Lars M. Steinmetz,Jef D. Boeke,Yizhi Cai
Cell  Published:November 08, 2023
DOI:https://doi.org/10.1016/j.cell.2023.10.015

Highlights

•Designed, built, and characterized a neochromosome with 275 tRNA genes in yeast
•Additional tRNA genes burden the host cell, causing deletions or increased ploidy
•Chemical tRNA neochromosome extraction enables transplantation into new yeast strains
•Functional analysis reveals insights into tRNA and chromosomal biology

Summary

Here, we report the design, construction, and characterization of a tRNA neochromosome, a designer chromosome that functions as an additional, de novo counterpart to the native complement of Saccharomyces cerevisiae. Intending to address one of the central design principles of the Sc2.0 project, the ∼190-kb tRNA neochromosome houses all 275 relocated nuclear tRNA genes. To maximize stability, the design incorporates orthogonal genetic elements from non-S. cerevisiae yeast species. Furthermore, the presence of 283 rox recombination sites enables an orthogonal tRNA SCRaMbLE system. Following construction in yeast, we obtained evidence of a potent selective force, manifesting as a spontaneous doubling in cell ploidy. Furthermore, tRNA sequencing, transcriptomics, proteomics, nucleosome mapping, replication profiling, FISH, and Hi-C were undertaken to investigate questions of tRNA neochromosome behavior and function. Its construction demonstrates the remarkable tractability of the yeast model and opens up opportunities to directly test hypotheses surrounding these essential non-coding RNAs.

Graphical abstract

Figure thumbnail fx1

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細胞遺伝子工学
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