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

TY - JOUR

T1 - Multi-omic based production strain improvement (MOBpsi) for bio-manufacturing of toxic chemicals

AU - Webb, Joseph P

AU - Paiva, Ana Carolina

AU - Rossoni, Luca

AU - Alstrom-Moore, Amias

AU - Springthorpe, Vicki

AU - Vaud, Sophie

AU - Yeh, Vivien

AU - Minde, David-Paul

AU - Langer, Sven

AU - Walker, Heather

AU - Hounslow, Andrea

AU - Nielsen, David R

AU - Larson, Tony

AU - Lilley, Kathryn

AU - Stephens, Gill

AU - Thomas, Gavin H

AU - Bonev, Boyan B

AU - Kelly, David J

AU - Conradie, Alex

AU - Green, Jeffrey

N1 - Copyright © 2022 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

PY - 2022/3/11

Y1 - 2022/3/11

N2 - 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.

AB - 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.

U2 - 10.1016/j.ymben.2022.03.004

DO - 10.1016/j.ymben.2022.03.004

M3 - Article

C2 - 35289291

SN - 1096-7176

VL - 72

SP - 133

EP - 149

JO - Metabolic engineering

JF - Metabolic engineering

ER -