Application of genome-scale models of metabolism and expression to the simulation and design of recombinant organisms DOI Creative Commons
Omid Oftadeh, Vassily Hatzimanikatis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 15, 2023

Abstract The production of recombinant proteins in a host using synthetic constructs such as plasmids comes at the cost detrimental effects reduced growth, energetic inefficiencies, and other stress responses, collectively known metabolic stress. Increasing number copies foreign gene increases load but expression protein. Thus, there is trade-off between biomass product yield response to changes heterologous copy number. This work proposes computational method, rETFL (recombinant Expression Thermodynamic Flux), for analyzing predicting responses organisms introduction constructs. an extension ETFL formulations designed reconstruct models metabolism (ME-models). We have illustrated capabilities method four studies (i) capture growth reduction plasmid-containing E. coli protein production; (ii) explore plasmid varied; (iii) predict emergence overflow agreement with experimental data; (iv) investigate individual pathways enzymes affected by presence plasmid. anticipate that will serve comprehensive platform integrating available omics data making context-specific predictions can help optimize systems biopharmaceutical therapy.

Language: Английский

Co-utilization of saccharides in mixtures: Moving toward a new understanding of carbon metabolism in Streptococcus thermophilus DOI

C. Gasser,

P. Garault,

Christian Chervaux

et al.

Food Microbiology, Journal Year: 2022, Volume and Issue: 107, P. 104080 - 104080

Published: June 11, 2022

Language: Английский

Citations

8
Emergent Lag Phase in Flux-Regulation Models of Bacterial Growth DOI Creative Commons
Fiona Bate, Yumechris Amekan, Dmitri O. Pushkin

et al.

Bulletin of Mathematical Biology, Journal Year: 2023, Volume and Issue: 85(9)

Published: Aug. 14, 2023

Lag phase is observed in bacterial growth during a sudden change conditions: inhibited whilst cells adapt to the environment. Bi-phasic, or diauxic commonly exhibited by many species. In presence of two sugars, initially grow consuming preferred sugar then undergo lag before resuming on second. Biomass increase characterised curve: exponential followed period no second growth. Recent literature lacks complete dynamic description, artificially modelling and employing non-physical representations precursor pools. Here, we formulate rational mechanistic model based flux-regulation/proteome partitioning with finite pool that reveals core mechanisms compact form. Unlike earlier systems, characteristic dynamics emerge as part solution, including phase. Focussing Escherichia coli glucose-lactose mixture show results accurately reproduce experiments. We for single strain E. coli, leads optimised biomass yields. However, intriguingly, competing strains not always best strategy. Our description can be generalised multiple different microorganisms investigate competition between species/strains.

Language: Английский

Citations

4
Carbon source priority and availability limit bidirectional electron transfer in freshwater mixed culture electrochemically active bacterial biofilms DOI Creative Commons

Karina Michalska,

Robert K. Brown, Uwe Schröder

et al.

Bioresources and Bioprocessing, Journal Year: 2023, Volume and Issue: 10(1)

Published: Sept. 20, 2023

Abstract This study investigated, if a mixed electroactive bacterial (EAB) culture cultivated heterotrophically at positive applied potential could be adapted from oxidative to reductive or bidirectional extracellular electron transfer (EET). To this end, periodic reversal regime between − 0.5 and 0.2 V vs. Ag/AgCl was applied. yielded biofilm detachment mediated electroautotrophic EET in combination with carbonate, i.e., dissolved CO 2 , as the sole carbon source, whereby emerged (S1) contained previously unknown EAB. Using acetate (S2) well mixture of carbonate (S3) main sources primarily alternating electrogenic organoheterotropic metabolism higher maximum oxidation current densities recorded for media, exceeding on average 1 mA cm −2 . More frequent polarization resulted increase by about 50% S2-BES 80% S3-BES, comparison half-batch polarization. The EAB cultures developed accordingly, S1 represented mostly aerobes (84.8%) being very different composition S2 S3, dominated anaerobes (96.9 96.5%, respectively). S3 biofilms remained attached electrodes. There only minor evidence fully reversible EET. In conclusion three triplicates fed organic and/or inorganic demonstrated two forms diauxie: Firstly, S1-BES showed preference electrode donor via Secondly, S3-BES c-source, long available, switching reduction, when depleted. Graphical

Language: Английский

Citations

4
Using resource constraints derived from genomic and proteomic data in metabolic network models DOI Creative Commons
Kobe De Becker, Niccolò Totis, Kristel Bernaerts

et al.

Current Opinion in Systems Biology, Journal Year: 2021, Volume and Issue: 29, P. 100400 - 100400

Published: Oct. 22, 2021

The increasing amount of available high-content data in genomics, proteomics, and metabolomics has significantly improved the predictive power model accuracy genome-scale metabolic network models recent years. We review constraint-based modeling approaches that incorporate genomics proteomics to form resource allocation models. Different build related enzyme-constrained are discussed evaluated with respect differences regarding features. In addition, an overview required construct, simulate validate for different is given, together a list relevant databases.

Language: Английский

Citations

10
Application of genome-scale models of metabolism and expression to the simulation and design of recombinant organisms DOI Creative Commons
Omid Oftadeh, Vassily Hatzimanikatis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 15, 2023

Abstract The production of recombinant proteins in a host using synthetic constructs such as plasmids comes at the cost detrimental effects reduced growth, energetic inefficiencies, and other stress responses, collectively known metabolic stress. Increasing number copies foreign gene increases load but expression protein. Thus, there is trade-off between biomass product yield response to changes heterologous copy number. This work proposes computational method, rETFL (recombinant Expression Thermodynamic Flux), for analyzing predicting responses organisms introduction constructs. an extension ETFL formulations designed reconstruct models metabolism (ME-models). We have illustrated capabilities method four studies (i) capture growth reduction plasmid-containing E. coli protein production; (ii) explore plasmid varied; (iii) predict emergence overflow agreement with experimental data; (iv) investigate individual pathways enzymes affected by presence plasmid. anticipate that will serve comprehensive platform integrating available omics data making context-specific predictions can help optimize systems biopharmaceutical therapy.

Language: Английский

Citations

3