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/M005690/1
• 负责人: Yizhi Cai
• 金额: $ 79.69万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM005690%2F1
• 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.

合成酵母基因组的诱导进化（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，更重要的是用于产生和理解工业上高价值的表型。Sc2.0中的合成染色体允许通过合成染色体重排和loxP介导的进化修饰（SCRaMbLE）进行快速和全面的基因组进化。SCRaMbLE将在美国和欧洲使用恒化器和批量转移方法，在这里开发用于生物燃料和生物技术的高价值表型的菌株。将开发新染色体和基因类正交SCRaMbLE技术。进化轨迹将被分析以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性的进化驱动因素，并有可能进一步优化。IESY建立在国际Sc2.0联盟独特的资源基础上，将成为高效进化高价值表型的国际资源。该项目代表了合成生物学的一种新范式，其中基因组被预先编程以探索组合多样性空间，从而进化出新的有用功能。

项目成果

YeastFab: the design and construction of standard biological parts for metabolic engineering in Saccharomyces cerevisiae.

• DOI: 10.1093/nar/gkv464
• 发表时间: 2015-07-27
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Guo Y;Dong J;Zhou T;Auxillos J;Li T;Zhang W;Wang L;Shen Y;Luo Y;Zheng Y;Lin J;Chen GQ;Wu Q;Cai Y;Dai J
• 通讯作者: Dai J

A feeling for the (micro)organism? Yeastiness, organism agnosticism and whole genome synthesis

对（微生物）有机体有感觉吗？

• DOI: 10.1080/14636778.2020.1736537
• 发表时间: 2020
• 期刊: New Genetics and Society
• 影响因子: 1.8
• 作者: Calvert J

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

Methods to Synthesize Large DNA Fragments for a Synthetic Yeast Genome.

• DOI: 10.1101/pdb.prot080978
• 发表时间: 2017-03
• 期刊: Cold Spring Harbor protocols
• 作者: Yizhi Cai;Junbiao Dai

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