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

Reconstructing organisms in silico: genome-scale models and their emerging applications DOI
Xin Fang, Colton J. Lloyd, Bernhard Ø. Palsson

et al.

Nature Reviews Microbiology, Journal Year: 2020, Volume and Issue: 18(12), P. 731 - 743

Published: Sept. 21, 2020

Language: Английский

Citations

233
A genome-scale metabolic model of Saccharomyces cerevisiae that integrates expression constraints and reaction thermodynamics DOI Creative Commons
Omid Oftadeh, Pierre Salvy, María Masid

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Aug. 9, 2021

Eukaryotic organisms play an important role in industrial biotechnology, from the production of fuels and commodity chemicals to therapeutic proteins. To optimize these systems, a mathematical approach can be used integrate description multiple biological networks into single model for cell analysis engineering. One most accurate models systems include Expression Thermodynamics FLux (ETFL), which efficiently integrates RNA protein synthesis with traditional genome-scale metabolic models. However, ETFL is so far only applicable E. coli. adapt this Saccharomyces cerevisiae, we developed yETFL, augmented original formulation additional considerations biomass composition, compartmentalized cellular expression system, energetic costs processes. We demonstrated ability yETFL predict maximum growth rate, essential genes, phenotype overflow metabolism. envision that presented extended wide range eukaryotic benefit academic research.

Language: Английский

Citations

72
Changes in interactions over ecological time scales influence single-cell growth dynamics in a metabolically coupled marine microbial community DOI Creative Commons
Michael Daniels, Simon van Vliet, Martin Ackermann

et al.

The ISME Journal, Journal Year: 2023, Volume and Issue: 17(3), P. 406 - 416

Published: Jan. 7, 2023

Abstract Microbial communities thrive in almost all habitats on earth. Within these communities, cells interact through the release and uptake of metabolites. These interactions can have synergistic or antagonistic effects individual community members. The collective metabolic activity microbial leads to changes their local environment. As environment over time, nature between change. We currently lack understanding how such dynamic feedbacks affect growth dynamics microbes as a whole. Here we study mediated by exchange metabolites change time within simple marine community. used microfluidic-based approach that allows us disentangle effect from they respond found two species—a degrader chitin cross-feeder consumes by-products—changes dynamically modify Cells initially positively then start compete at later stages growth. Our results demonstrate microorganisms are not static depend state environment, emphasizing importance disentangling modifications affects species interactions. This experimental shed new light interspecies scale up level processes natural environments.

Language: Английский

Citations

34
AMiGA: Software for Automated Analysis of Microbial Growth Assays DOI Creative Commons
Firas S. Midani, James Collins, Robert A. Britton

et al.

mSystems, Journal Year: 2021, Volume and Issue: 6(4)

Published: July 13, 2021

Our current understanding of microbial physiology relies on the simple method measuring populations’ sizes over time and under different conditions. Many advances have increased throughput those assays enabled study nonlab-adapted microbes diverse conditions that widely affect their growth dynamics.

Language: Английский

Citations

49
Developmental energetics: Energy expenditure, budgets and metabolism during animal embryogenesis DOI Creative Commons
Suhrid Ghosh,

Anna Körte,

Giulia Serafini

et al.

Seminars in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 138, P. 83 - 93

Published: March 19, 2022

Developing embryos are metabolically active, open systems that constantly exchange matter and energy with their environment. They function out of thermodynamic equilibrium continuously use metabolic pathways to obtain from maternal nutrients, in order fulfill the energetic requirements growth development. While an increasing number studies highlight role metabolism different developmental contexts, physicochemical basis embryogenesis, or how cellular processes act together transform a zygote into adult organism, remains unknown. As we better understanding metabolism, benefit current technology development, it is promising time revisit cost development principles may govern embryogenesis. Here, review recent advances methodology measure infer parameters developing embryos. We potential common pattern embryonic expenditure strategy across animal discuss challenges questions energetics.

Language: Английский

Citations

27
From microbiome composition to functional engineering, one step at a time DOI
Sebastian D. Burz, Senka Čaušević, Alma Dal Co

et al.

Microbiology and Molecular Biology Reviews, Journal Year: 2023, Volume and Issue: 87(4)

Published: Nov. 10, 2023

SUMMARY Communities of microorganisms (microbiota) are present in all habitats on Earth and relevant for agriculture, health, climate. Deciphering the mechanisms that determine microbiota dynamics functioning within context their respective environments or hosts (the microbiomes) is crucially important. However, sheer taxonomic, metabolic, functional, spatial complexity most microbiomes poses substantial challenges to advancing our knowledge these mechanisms. While nucleic acid sequencing technologies can chart composition with high precision, we mostly lack information about functional roles interactions each strain a given microbiome. This limits ability predict microbiome function natural and, case dysfunction dysbiosis, redirect onto stable paths. Here, will discuss systematic approach (dubbed N + 1/N−1 concept) enable step-by-step dissection assembly functioning, as well intervention procedures introduce eliminate one particular microbial at time. The N+1/N−1 concept informed by invasion events selects culturable, genetically accessible microbes well-annotated genomes proliferation decline defined synthetic and/or complex microbiota. enables harnessing classical microbiological diversity approaches, omics tools mathematical modeling decipher underlying outcomes. Application this further provides stepping stones benchmarks structure analyses more strategies.

Language: Английский

Citations

15
Biodiversity is enhanced by sequential resource utilization and environmental fluctuations via emergent temporal niches DOI Creative Commons
Blox Bloxham, Hyunseok Lee, Jeff Gore

et al.

PLoS Computational Biology, Journal Year: 2024, Volume and Issue: 20(5), P. e1012049 - e1012049

Published: May 13, 2024

How natural communities maintain their remarkable biodiversity and which species survive in complex are central questions ecology. Resource competition models successfully explain many phenomena but typically predict only as resources can coexist. Here, we demonstrate that sequential resource utilization, or diauxie, with periodic growth cycles support more than resources. We explore how modify own environments by sequentially depleting to form sequences of temporal niches, intermediately depleted environments. Biodiversity is enhanced when community-driven environmental fluctuations modulate the depletion order produce different niches on each cycle. Community-driven under constant conditions rare, exploring them illuminates niche structure emerges from utilization. With fluctuations, find most have stably coexisting survivors accurately predicted same following a distinct optimal strategy. Our results thus present new niche-based approach understanding highly diverse fluctuating communities.

Language: Английский

Citations

5
Genome-scale models of metabolism and expression predict the metabolic burden of recombinant protein expression DOI Creative Commons
Omid Oftadeh, Vassily Hatzimanikatis

Metabolic Engineering, Journal Year: 2024, Volume and Issue: 84, P. 109 - 116

Published: June 15, 2024

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 burden. 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

5
Advances in constraint-based models: methods for improved predictive power based on resource allocation constraints DOI Creative Commons
Eduard J. Kerkhoven

Current Opinion in Microbiology, Journal Year: 2022, Volume and Issue: 68, P. 102168 - 102168

Published: June 9, 2022

The concept of metabolic models with resource allocation constraints has been around for over a decade and clear advantages even when implementation is relatively rudimentary. Nonetheless, the number organisms which such model reconstructed low. Various approaches exist, from coarse-grained consideration enzyme usage to fine-grained description protein translation. These are reviewed here, particular focus on user-friendly solutions that can introduce any organism. availability kcat data major hurdle, where recent advances might help fill in numerous gaps exist this data, especially nonmodel organisms.

Language: Английский

Citations

20
Chemodiversity controls microbial assimilation of soil organic carbon: A theoretical model DOI
Jacob Weverka, Holly V. Moeller, Joshua P. Schimel

et al.

Soil Biology and Biochemistry, Journal Year: 2023, Volume and Issue: 187, P. 109161 - 109161

Published: Aug. 25, 2023

Language: Английский

Citations

11