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OptDesign:在生化生产的应变工程中确定最佳设计策略。

OptDesign: Identifying Optimum Design Strategies in Strain Engineering for Biochemical Production.

机构信息

Department of Computing Science, University of Aberdeen, Aberdeen AB24 3FX, U.K.

Institute for Integrative Systems Biology, UV-CSIC, Valencia 46980, Spain.

出版信息

ACS Synth Biol. 2022 Apr 15;11(4):1531-1541. doi: 10.1021/acssynbio.1c00610. Epub 2022 Apr 7.

Abstract

Computational tools have been widely adopted for strain optimization in metabolic engineering, contributing to numerous success stories of producing industrially relevant biochemicals. However, most of these tools focus on single metabolic intervention strategies (either gene/reaction knockout or amplification alone) and rely on hypothetical optimality principles (e.g., maximization of growth) and precise gene expression (e.g., fold changes) for phenotype prediction. This paper introduces OptDesign, a new two-step strain design strategy. In the first step, OptDesign selects regulation candidates that have a noticeable flux difference between the wild type and production strains. In the second step, it computes optimal design strategies with limited manipulations (combining regulation and knockout), leading to high biochemical production. The usefulness and capabilities of OptDesign are demonstrated for the production of three biochemicals in using the latest genome-scale metabolic model iML1515, showing highly consistent results with previous studies while suggesting new manipulations to boost strain performance. The source code is available at https://github.com/chang88ye/OptDesign.

摘要

计算工具已被广泛应用于代谢工程中的菌株优化,为生产具有工业相关性的生物化学物质的众多成功案例做出了贡献。然而,这些工具大多集中在单一的代谢干预策略(单独的基因/反应敲除或扩增)上,并且依赖于假设的最优性原则(例如,最大生长)和精确的基因表达(例如,倍数变化)进行表型预测。本文介绍了 OptDesign,这是一种新的两步菌株设计策略。在第一步中,OptDesign 选择在野生型和生产菌株之间具有明显通量差异的调控候选物。在第二步中,它计算具有有限操作(结合调控和敲除)的最佳设计策略,从而实现高生物化学产量。使用最新的基因组尺度代谢模型 iML1515,在 中对三种生物化学物质的生产证明了 OptDesign 的有用性和能力,结果与先前的研究高度一致,同时还提出了新的操作来提高菌株性能。源代码可在 https://github.com/chang88ye/OptDesign 上获得。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa3/9016760/b7405e680ffe/sb1c00610_0002.jpg

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