Yeast metabolic chassis designs for diverse biotechnological products.
Yeast metabolic chassis designs for diverse biotechnological products.
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DOI：
10.1038/srep29694
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发表时间：
2016-07-19
影响因子：
4.6
通讯作者：
Patil KR
中科院分区：
文献类型：
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作者：
Jouhten P;Boruta T;Andrejev S;Pereira F;Rocha I;Patil KR
已通过实验证明微生物生产途径的工业上重要的分子的多样性正在迅速增加。然而，经济上可行的生产细胞的开发是落后的，因为它需要宿主代谢的大量工程。因此，高度寻求适合于生产一系列分子的底盘菌株，但仍然难以捉摸。在这里，我们提出了一个基因组规模的代谢建模方法来设计底盘菌株酿酒酵母-一种广泛使用的微生物细胞工厂。对于涵盖广泛生物化学和应用的29种产品，我们确定了模块化代谢工程策略，用于将碳通量重新导向所需的产品。我们发现具有共同目标的不同产品系列构成了相应底盘单元的基础。设计策略包括通过前体和辅因子要求的相似性对产物进行分组的过表达靶点，以及导致非直观产物组的生长产物偶联的基因缺失策略。我们的结果揭示了在广泛使用的细胞工厂中生产各种产品所需的通量重新路由的范围和性质，并提供了构建预优化底盘菌株的蓝图。
The diversity of industrially important molecules for which microbial production routes have been experimentally demonstrated is rapidly increasing. The development of economically viable producer cells is, however, lagging behind, as it requires substantial engineering of the host metabolism. A chassis strain suitable for production of a range of molecules is therefore highly sought after but remains elusive. Here, we propose a genome-scale metabolic modeling approach to design chassis strains of Saccharomyces cerevisiae – a widely used microbial cell factory. For a group of 29 products covering a broad range of biochemistry and applications, we identified modular metabolic engineering strategies for re-routing carbon flux towards the desired product. We find distinct product families with shared targets forming the basis for the corresponding chassis cells. The design strategies include overexpression targets that group products by similarity in precursor and cofactor requirements, as well as gene deletion strategies for growth-product coupling that lead to non-intuitive product groups. Our results reveal the extent and the nature of flux re-routing necessary for producing a diverse range of products in a widely used cell factory and provide blueprints for constructing pre-optimized chassis strains.