Multi-omic based production strain improvement (MOBpsi) for bio-manufacturing of toxic chemicals.
Multi-omic based production strain improvement (MOBpsi) for bio-manufacturing of toxic chemicals.
复制标题
DOI：
10.1016/j.ymben.2022.03.004
复制
发表时间：
2022-03
影响因子：
8.4
通讯作者：
Joseph P. Webb;A. C. Paiva;L. Rossoni;Amias Alstrom-Moore;V. Springthorpe;Sophie Vaud;Vivien Yeh;David P. Minde;Sven Langer;Heather J. Walker;A. Hounslow;D. Nielsen;Tony Larson;K. Lilley;G. Stephens;G. H. Thomas;B. Bonev;D. Kelly;A. Conradie;J. Green
中科院分区：
文献类型：
--
作者：
Joseph P. Webb;A. C. Paiva;L. Rossoni;Amias Alstrom-Moore;V. Springthorpe;Sophie Vaud;Vivien Yeh;David P. Minde;Sven Langer;Heather J. Walker;A. Hounslow;D. Nielsen;Tony Larson;K. Lilley;G. Stephens;G. H. Thomas;B. Bonev;D. Kelly;A. Conradie;J. Green
用于细胞工厂代谢工程的稳健系统方法仍然难以捉摸。用于预测表型反应和机制的可用模型是不完整的，特别是在化合物毒性的背景下，这可能是实现目标产品高产率的重大障碍。本研究描述了一种基于多组学的生产菌株改进 (MOBpsi) 策略，该策略的特点是对补料分批发酵进行集成时间分辨系统分析。作为案例研究，MOBpsi 被应用于提高生产商品化学品苯乙烯的大肠杆菌工厂的性能。苯乙烯可以通过由苯丙氨酸解氨酶和阿魏酸脱羧酶组成的工程途径从苯丙氨酸生物制造。苯乙烯的毒性、疏水性和挥发性给生物生产带来了挑战。先前尝试创建耐苯乙烯E。通过有针对性的基因干预来治疗粘菌菌株已取得一定的成功。 MOBpsi 的应用确定了提高性能的新潜在目标，导致两种宿主菌株（大肠杆菌 NST74ΔaaeA 和 NST74ΔaaeA cpxPo）的苯乙烯产量增加。性能最佳的重新设计底盘 NST74ΔaaeA cpxPo 产生了约 3 倍的苯乙烯，并且在补料分批发酵中表现出更高的活力。因此，本案例研究证明了 MOBpsi 作为改善有毒化学品生物制造的系统工具的实用性。
Robust systematic approaches for the metabolic engineering of cell factories remain elusive. The available models for predicting phenotypical responses and mechanisms are incomplete, particularly within the context of compound toxicity that can be a significant impediment to achieving high yields of a target product. This study describes a Multi-Omic Based Production Strain Improvement (MOBpsi) strategy that is distinguished by integrated time-resolved systems analyses of fed-batch fermentations. As a case study, MOBpsiwas applied to improve the performance of anEscherichia colicell factory producing the commodity chemical styrene. Styrene can be bio-manufactured from phenylalanineviaan engineered pathway comprised of the enzymes phenylalanine ammonia lyase and ferulic acid decarboxylase. The toxicity, hydrophobicity, and volatility of styrene combine to make bio-production challenging. Previous attempts to create styrene tolerantE. colistrains by targeted genetic interventions have met with modest success. Application of MOBpsiidentified new potential targets for improving performance, resulting in two host strains (E. coliNST74ΔaaeAand NST74ΔaaeA cpxPo) with increased styrene production. The best performing re-engineered chassis, NST74ΔaaeA cpxPo, produced ∼3 × more styrene and exhibited increased viability in fed-batch fermentations. Thus, this case study demonstrates the utility of MOBpsias a systematic tool for improving the bio-manufacturing of toxic chemicals.