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

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

doi:10.1016/j.ymben.2022.03.004

Cited by 8 publications

(4 citation statements)

References 79 publications

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“…While not always accompanied by an immediate demonstration of an increased bioproductivity, recent studies often explore the multidisciplinary integration of metabolomics and other technologies to better understand biological systems and generate suggestions for strain improvement. In a recent study, Webb et al (2022) developed an approach involving the multi-omics integration of metabolomics, transcriptomics, proteomics, and lipidomics to identify potential targets for strain improvement and successfully demonstrated a 3-fold increase in styrene bioproduction. In another study, Zhang et al (2022) utilized a combination of metabolomics, genomics, and protein structure simulation to identify F6PPK in the “bifidus” pathway as a vital enzyme to confer osmotic stress tolerance in engineered Bifidobacterium bifidum .…”

Section: Recent Advances and Future Outlookmentioning

confidence: 99%

Metabolomics-driven strain improvement: A mini review

Iman

Herawati²,

Fukusaki³

et al. 2022

Front. Mol. Biosci.

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In recent years, mass spectrometry-based metabolomics has been established as a powerful and versatile technique for studying cellular metabolism by comprehensive analysis of metabolites in the cell. Although there are many scientific reports on the use of metabolomics for the elucidation of mechanism and physiological changes occurring in the cell, there are surprisingly very few reports on its use for the identification of rate-limiting steps in a synthetic biological system that can lead to the actual improvement of the host organism. In this mini review, we discuss different strategies for improving strain performance using metabolomics data and compare the application of metabolomics-driven strain improvement techniques in different host microorganisms. Finally, we highlight several success stories on the use of metabolomics-driven strain improvement strategies, which led to significant bioproductivity improvements.

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Section: Recent Advances and Future Outlookmentioning

confidence: 99%

Metabolomics-driven strain improvement: A mini review

Iman

Herawati²,

Fukusaki³

et al. 2022

Front. Mol. Biosci.

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“…Metabolic engineering allows rewiring of cellular metabolism to increase product titers by enhancing precursor supply 3 , 4 , tackling co-factor limitations 5 – 7 , interrupting competitive pathways 8 , 9 , preventing buildup of toxic intermediates 10 and improving heterologous pathway flux 11 . Over the past years, several tools and strategies have been developed to facilitate yield optimization, including chassis strain improvement 12 – 14 , directed mutagenesis 15 – 17 , synthetic compartmentalization 18 , 19 and pathway gene expression optimization 20 .…”

Section: Introductionmentioning

confidence: 99%

Combinatorial optimization of gene expression through recombinase-mediated promoter and terminator shuffling in yeast

Cautereels,

Smets,

Bircham

et al. 2024

Nat Commun

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Microbes are increasingly employed as cell factories to produce biomolecules. This often involves the expression of complex heterologous biosynthesis pathways in host strains. Achieving maximal product yields and avoiding build-up of (toxic) intermediates requires balanced expression of every pathway gene. However, despite progress in metabolic modeling, the optimization of gene expression still heavily relies on trial-and-error. Here, we report an approach for in vivo, multiplexed Gene Expression Modification by LoxPsym-Cre Recombination (GEMbLeR). GEMbLeR exploits orthogonal LoxPsym sites to independently shuffle promoter and terminator modules at distinct genomic loci. This approach facilitates creation of large strain libraries, in which expression of every pathway gene ranges over 120-fold and each strain harbors a unique expression profile. When applied to the biosynthetic pathway of astaxanthin, an industrially relevant antioxidant, a single round of GEMbLeR improved pathway flux and doubled production titers. Together, this shows that GEMbLeR allows rapid and efficient gene expression optimization in heterologous biosynthetic pathways, offering possibilities for enhancing the performance of microbial cell factories.

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“…Microbial styrene production has been widely studied by several research groups [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. Using E. coli as the host strain, endogenous l-phenylalanine (Phe) is converted to styrene via trans -cinnamic acid (Cin) by the endogenous sequential reactions of L-phenylalanine ammonia lyase (PAL) and ferulic acid decarboxylase (FDC).…”

Section: Introductionmentioning

confidence: 99%

Styrene Production in Genetically Engineered Escherichia coli in a Two-Phase Culture

Noda,

Fujiwara,

Mori

et al. 2024

BioTech

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Styrene is an important industrial chemical. Although several studies have reported microbial styrene production, the amount of styrene produced in batch cultures can be increased. In this study, styrene was produced using genetically engineered Escherichia coli. First, we evaluated five types of phenylalanine ammonia lyases (PALs) from Arabidopsis thaliana (AtPAL) and Brachypodium distachyon (BdPAL) for their ability to produce trans-cinnamic acid (Cin), a styrene precursor. AtPAL2-expressing E. coli produced approximately 700 mg/L of Cin and we found that BdPALs could convert Cin into styrene. To assess styrene production, we constructed an E. coli strain that co-expressed AtPAL2 and ferulic acid decarboxylase from Saccharomyces cerevisiae. After a biphasic culture with oleyl alcohol, styrene production and yield from glucose were 3.1 g/L and 26.7% (mol/mol), respectively, which, to the best of our knowledge, are the highest values obtained in batch cultivation. Thus, this strain can be applied to the large–scale industrial production of styrene.

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

Cited by 8 publications

References 79 publications

Metabolomics-driven strain improvement: A mini review

Metabolomics-driven strain improvement: A mini review

Combinatorial optimization of gene expression through recombinase-mediated promoter and terminator shuffling in yeast

Styrene Production in Genetically Engineered Escherichia coli in a Two-Phase Culture

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