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

Abstract

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 (US)
Pages (from-to)133-149
Number of pages17
JournalMetabolic Engineering
Volume72
DOIs
StatePublished - Jul 2022
Externally publishedYes

Keywords

  • Biotechnology
  • Cell factory
  • Lipidomics
  • Proteomics
  • Styrene
  • Transcriptomics

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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