CFSA:作为应变设计指南的通量取样比较分析

IF 3.7 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Metabolic Engineering Communications Pub Date : 2024-06-24 DOI:10.1016/j.mec.2024.e00244
R.P. van Rosmalen , S. Moreno-Paz , Z.E. Duman-Özdamar, M. Suarez-Diez
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引用次数: 0

摘要

微生物新陈代谢的基因组尺度代谢模型已被广泛用于指导微生物细胞工厂的设计,但许多现有的菌株设计算法往往无法产生一个可逐步实施和验证的性能改进目标缩减列表。我们提出的比较通量取样分析(CFSA)是一种菌株设计方法,它基于对最大或接近最大生长和生产表型对应的完整代谢空间进行广泛比较。统计分析对这种比较进行了补充,以确定通量发生变化的反应,并建议将这些反应作为基因干预的目标,包括上调、下调和基因缺失。我们将 CFSA 应用于油菜酵母菌(Cutaneotrichosporon oleaginosus)生产脂类和柚皮苷的过程,确定了与以往研究一致的工程目标以及新的干预措施。CFSA 是一种易于使用且稳健的方法,可为生长不耦合生产提出潜在的代谢工程目标,并可应用于微生物细胞工厂的设计。
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CFSA: Comparative flux sampling analysis as a guide for strain design

Genome-scale metabolic models of microbial metabolism have extensively been used to guide the design of microbial cell factories, still, many of the available strain design algorithms often fail to produce a reduced list of targets for improved performance that can be implemented and validated in a step-wise manner. We present Comparative Flux Sampling Analysis (CFSA), a strain design method based on the extensive comparison of complete metabolic spaces corresponding to maximal or near-maximal growth and production phenotypes. The comparison is complemented by statistical analysis to identify reactions with altered flux that are suggested as targets for genetic interventions including up-regulations, down-regulations and gene deletions. We applied CFSA to the production of lipids by Cutaneotrichosporon oleaginosus and naringenin by Saccharomyces cerevisiae identifying engineering targets in agreement with previous studies as well as new interventions. CFSA is an easy-to-use, robust method that suggests potential metabolic engineering targets for growth-uncoupled production that can be applied to the design of microbial cell factories.

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来源期刊
Metabolic Engineering Communications
Metabolic Engineering Communications Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
13.30
自引率
1.90%
发文量
22
审稿时长
18 weeks
期刊介绍: Metabolic Engineering Communications, a companion title to Metabolic Engineering (MBE), is devoted to publishing original research in the areas of metabolic engineering, synthetic biology, computational biology and systems biology for problems related to metabolism and the engineering of metabolism for the production of fuels, chemicals, and pharmaceuticals. The journal will carry articles on the design, construction, and analysis of biological systems ranging from pathway components to biological complexes and genomes (including genomic, analytical and bioinformatics methods) in suitable host cells to allow them to produce novel compounds of industrial and medical interest. Demonstrations of regulatory designs and synthetic circuits that alter the performance of biochemical pathways and cellular processes will also be presented. Metabolic Engineering Communications complements MBE by publishing articles that are either shorter than those published in the full journal, or which describe key elements of larger metabolic engineering efforts.
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