Multi-omic based production strain improvement (MOBpsi) for bio-manufacturing of toxic chemicals

Joseph P Webb, Ana Carolina Paiva, Luca Rossoni, Amias Alstrom-Moore, Vicki Springthorpe, Sophie Vaud, Vivien Yeh, David-Paul Minde, Sven Langer, Heather Walker, Andrea Hounslow, David R Nielsen, Tony Larson, Kathryn Lilley, Gill Stephens, Gavin H Thomas, Boyan B Bonev, David J Kelly, Alex Conradie, Jeffrey Green

Research output: Contribution to journalArticlepeer-review


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, MOBpsi was applied to improve the performance of an Escherichia coli cell factory producing the commodity chemical styrene. Styrene can be bio-manufactured from phenylalanine via an 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 tolerant E. coli strains by targeted genetic interventions have met with modest success. Application of MOBpsi identified new potential targets for improving performance, resulting in two host strains (E. coli NST74ΔaaeA and 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 MOBpsi as a systematic tool for improving the bio-manufacturing of toxic chemicals.

Original languageEnglish
Pages (from-to)133-149
Number of pages17
JournalMetabolic engineering
Early online date11 Mar 2022
Publication statusE-pub ahead of print - 11 Mar 2022

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