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Utilising datasheets for the informed automated design and build of a synthetic metabolic pathway

BACKGROUND: The automation of modular cloning methodologies permits the assembly of many genetic designs. Utilising characterised biological parts aids in the design and redesign of genetic pathways. The characterisation information held on datasheets can be used to determine whether a biological pa...

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Autores principales: Exley, Kealan, Reynolds, Christopher Robert, Suckling, Lorna, Chee, Soo Mei, Tsipa, Argyro, Freemont, Paul S., McClymont, David, Kitney, Richard Ian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339355/
https://www.ncbi.nlm.nih.gov/pubmed/30675181
http://dx.doi.org/10.1186/s13036-019-0141-z
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author Exley, Kealan
Reynolds, Christopher Robert
Suckling, Lorna
Chee, Soo Mei
Tsipa, Argyro
Freemont, Paul S.
McClymont, David
Kitney, Richard Ian
author_facet Exley, Kealan
Reynolds, Christopher Robert
Suckling, Lorna
Chee, Soo Mei
Tsipa, Argyro
Freemont, Paul S.
McClymont, David
Kitney, Richard Ian
author_sort Exley, Kealan
collection PubMed
description BACKGROUND: The automation of modular cloning methodologies permits the assembly of many genetic designs. Utilising characterised biological parts aids in the design and redesign of genetic pathways. The characterisation information held on datasheets can be used to determine whether a biological part meets the design requirements. To manage the design of genetic pathways, researchers have turned to modelling-based computer aided design software tools. RESULT: An automated workflow has been developed for the design and build of heterologous metabolic pathways. In addition, to demonstrate the powers of electronic datasheets we have developed software which can transfer part information from a datasheet to the Design of Experiment software JMP. To this end we were able to use Design of Experiment software to rationally design and test randomised samples from the design space of a lycopene pathway in E. coli. This pathway was optimised by individually modulating the promoter strength, RBS strength, and gene order targets. CONCLUSION: The use of standardised and characterised biological parts will empower a design-oriented synthetic biology for the forward engineering of heterologous expression systems. A Design of Experiment approach streamlines the design-build-test cycle to achieve optimised solutions in biodesign. Developed automated workflows provide effective transfer of information between characterised information (in the form of datasheets) and DoE software. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13036-019-0141-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-63393552019-01-23 Utilising datasheets for the informed automated design and build of a synthetic metabolic pathway Exley, Kealan Reynolds, Christopher Robert Suckling, Lorna Chee, Soo Mei Tsipa, Argyro Freemont, Paul S. McClymont, David Kitney, Richard Ian J Biol Eng Methodology BACKGROUND: The automation of modular cloning methodologies permits the assembly of many genetic designs. Utilising characterised biological parts aids in the design and redesign of genetic pathways. The characterisation information held on datasheets can be used to determine whether a biological part meets the design requirements. To manage the design of genetic pathways, researchers have turned to modelling-based computer aided design software tools. RESULT: An automated workflow has been developed for the design and build of heterologous metabolic pathways. In addition, to demonstrate the powers of electronic datasheets we have developed software which can transfer part information from a datasheet to the Design of Experiment software JMP. To this end we were able to use Design of Experiment software to rationally design and test randomised samples from the design space of a lycopene pathway in E. coli. This pathway was optimised by individually modulating the promoter strength, RBS strength, and gene order targets. CONCLUSION: The use of standardised and characterised biological parts will empower a design-oriented synthetic biology for the forward engineering of heterologous expression systems. A Design of Experiment approach streamlines the design-build-test cycle to achieve optimised solutions in biodesign. Developed automated workflows provide effective transfer of information between characterised information (in the form of datasheets) and DoE software. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13036-019-0141-z) contains supplementary material, which is available to authorized users. BioMed Central 2019-01-18 /pmc/articles/PMC6339355/ /pubmed/30675181 http://dx.doi.org/10.1186/s13036-019-0141-z Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Methodology
Exley, Kealan
Reynolds, Christopher Robert
Suckling, Lorna
Chee, Soo Mei
Tsipa, Argyro
Freemont, Paul S.
McClymont, David
Kitney, Richard Ian
Utilising datasheets for the informed automated design and build of a synthetic metabolic pathway
title Utilising datasheets for the informed automated design and build of a synthetic metabolic pathway
title_full Utilising datasheets for the informed automated design and build of a synthetic metabolic pathway
title_fullStr Utilising datasheets for the informed automated design and build of a synthetic metabolic pathway
title_full_unstemmed Utilising datasheets for the informed automated design and build of a synthetic metabolic pathway
title_short Utilising datasheets for the informed automated design and build of a synthetic metabolic pathway
title_sort utilising datasheets for the informed automated design and build of a synthetic metabolic pathway
topic Methodology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339355/
https://www.ncbi.nlm.nih.gov/pubmed/30675181
http://dx.doi.org/10.1186/s13036-019-0141-z
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