Perturbation Experiments: Approaches for Metabolic Pathway Analysis in Bioreactors.
Perturbation Experiments: Approaches for Metabolic Pathway Analysis in Bioreactors.
复制标题
DOI：
10.1007/10_2015_326
复制
发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Michael Weiner;Julia Tröndle;C. Albermann;G. Sprenger;D. Weuster‐Botz
中科院分区：
文献类型：
--
作者：
Michael Weiner;Julia Tröndle;C. Albermann;G. Sprenger;D. Weuster‐Botz
<？xm-replace_text{标题}?摘要近几十年来，微生物细胞的靶向代谢工程已成为生物工艺设计和优化的主要工具之一。为了成功应用，详细了解相关的代谢途径及其在细胞内的调节是必要的。由于体外实验不能正确地显示过程条件和行为，因此必须在体内收集有关细胞代谢状态的过程数据。为此，需要特殊的技术和方法。因此，大多数能够在体内表征代谢途径的技术依赖于摄动实验，可分为动态和稳态方法。为了避免任何过程干扰，在连续生产过程中同时干扰细胞代谢的方法是合理的。此外，微生物生产过程的快速动态放大了并行数据生成的需求。这些观点激发了在运行的生产反应器外进行多重代谢扰动实验的并行方法的发展。提出了一种适当的体内代谢途径表征方法，并举例应用于15 l规模的微生物l -苯丙氨酸生产过程。图形抽象
<?xm-replace_text {Heading}?>AbstractIn the last decades, targeted metabolic engineering of microbial cells has become one of the major tools in bioprocess design and optimization. For successful application, a detailed knowledge is necessary about the relevant metabolic pathways and their regulation inside the cells. Since in vitro experiments cannot display process conditions and behavior properly, process data about the cells’ metabolic state have to be collected in vivo. For this purpose, special techniques and methods are necessary. Therefore, most techniques enabling in vivo characterization of metabolic pathways rely on perturbation experiments, which can be divided into dynamic and steady-state approaches. To avoid any process disturbance, approaches which enable perturbation of cell metabolism in parallel to the continuing production process are reasonable. Furthermore, the fast dynamics of microbial production processes amplifies the need of parallelized data generation. These points motivate the development of a parallelized approach for multiple metabolic perturbation experiments outside the operating production reactor. An appropriate approach for in vivo characterization of metabolic pathways is presented and applied exemplarily to a microbial L-phenylalanine production process on a 15 L-scale.Graphical Abstract