14-ERASynBio - IESY - Inducible Evolution of Synthetic Yeast genomes

14-ERASynBio - IESY - 合成酵母基因组的诱导进化

• 批准号: BB/M005690/2
• 负责人: Yizhi Cai
• 金额: $ 10.12万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM005690%2F2
• 关键词: 14; ERASynBio; IESY; Inducible; Evolution

Induced Evolution of Synthetic Yeast genomes (IESY) will use the first synthetic eukaryote, Saccharomyces cerevisiae 2.0 (Sc2.0), as a platform for metabolic engineering and genome minimization, and more importantly for generating and understanding industrially high-value phenotypes. Synthetic chromosomes in Sc2.0 permit rapid and comprehensive genome evolution through synthetic chromosome rearrangement and modification by loxP-mediated evolution (SCRaMbLE). SCRaMbLE will be exploited here to evolve strains selected for high-value phenotypes for biofuels and biotechnology, using both chemostats and batch transfer methods in the USA and Europe. Technologies for neochromosomes and orthogonal SCRaMbLE of gene classes will be developed. Evolutionary trajectories will be analysed to relate genome structure with genome function: DNA sequencing will reveal the genome sequence, rearrangements, and copy number changes in the evolved strains; chromosome conformation capture will show how massive rearrangements affect 3D structure; and deep sequencing technologies will relate sequence and structure to gene expression and isoform abundance. Computational analysis will identify the evolutionary drivers for high fitness, with the potential for further optimization. IESY builds on resources uniquely available from the international Sc2.0 consortium and will be an international resource for efficient evolution of high-value phenotypes. This project represents a new paradigm in synthetic biology in which a genome is pre-programmed to explore combinatorial diversity space to evolve new and useful function.

合成酵母基因组诱导进化 (IESY) 将使用第一个合成真核生物酿酒酵母 2.0 (Sc2.0) 作为代谢工程和基因组最小化的平台，更重要的是用于生成和理解工业高价值表型。 Sc2.0 中的合成染色体通过 loxP 介导的进化 (SCRaMbLE) 进行合成染色体重排和修饰，允许快速、全面的基因组进化。 SCRaMbLE 将在美国和欧洲使用恒化器和批量转移方法，用于进化为生物燃料和生物技术的高价值表型选择的菌株。将开发新染色体和基因类别正交 SCRaMbLE 技术。将分析进化轨迹，将基因组结构与基因组功能联系起来：DNA测序将揭示进化菌株中的基因组序列、重排和拷贝数变化；染色体构象捕获将显示大规模重排如何影响 3D 结构；深度测序技术将序列和结构与基因表达和亚型丰度联系起来。计算分析将确定高适应度的进化驱动因素，并具有进一步优化的潜力。 IESY 以国际 Sc2.0 联盟独有的资源为基础，将成为高价值表型高效进化的国际资源。该项目代表了合成生物学的新范例，其中基因组被预先编程以探索组合多样性空间以进化新的有用的功能。

项目成果

Designing with living systems in the synthetic yeast project.

• DOI: 10.1038/s41467-018-05332-z
• 发表时间: 2018-07-27
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Szymanski E;Calvert J
• 通讯作者: Calvert J

Synthetic genomics: a new venture to dissect genome fundamentals and engineer new functions.

• DOI: 10.1016/j.cbpa.2018.04.002
• 发表时间: 2018-10
• 期刊: Current opinion in chemical biology
• 影响因子: 7.8
• 作者: Schindler D;Dai J;Cai Y
• 通讯作者: Cai Y

Genetic Constructor: An Online DNA Design Platform.

Genetic Constructor：在线 DNA 设计平台。

• DOI: 10.1021/acssynbio.7b00236
• 发表时间: 2017
• 期刊: ACS synthetic biology
• 影响因子: 4.7
• 作者: Bates M

Rapid pathway prototyping and engineering using in vitro and in vivo synthetic genome SCRaMbLE-in methods.

使用体外和体内合成基因组 SCRaMbLE-in 方法进行快速途径原型设计和工程设计

• DOI: 10.1038/s41467-018-04254-0
• 发表时间: 2018-05-22
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Liu W;Luo Z;Wang Y;Pham NT;Tuck L;Pérez-Pi I;Liu L;Shen Y;French C;Auer M;Marles-Wright J;Dai J;Cai Y
• 通讯作者: Cai Y

Leaf LIMS: A Flexible Laboratory Information Management System with a Synthetic Biology Focus.

Leaf LIMS：以合成生物学为重点的灵活实验室信息管理系统。

• DOI: 10.1021/acssynbio.7b00212
• 发表时间: 2017
• 期刊: ACS synthetic biology
• 影响因子: 4.7
• 作者: Craig T