Responses of Synechocystis sp. PCC 6803 to heterologous biosynthetic pathways

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Responses of Synechocystis sp. PCC 6803 to heterologous biosynthetic pathways. / Vavitsas, Konstantinos; Rue, Emil Østergaard; Stefánsdóttir, Lára Kristín; Gnanasekaran, Thiyagarajan; Blennow, Andreas; Crocoll, Christoph; Gudmundsson, Steinn; Jensen, Poul Erik.

I: Microbial Cell Factories, Bind 16, Nr. 1, 140, 2017.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Vavitsas, K, Rue, EØ, Stefánsdóttir, LK, Gnanasekaran, T, Blennow, A, Crocoll, C, Gudmundsson, S & Jensen, PE 2017, 'Responses of Synechocystis sp. PCC 6803 to heterologous biosynthetic pathways', Microbial Cell Factories, bind 16, nr. 1, 140. https://doi.org/10.1186/s12934-017-0757-y

APA

Vavitsas, K., Rue, E. Ø., Stefánsdóttir, L. K., Gnanasekaran, T., Blennow, A., Crocoll, C., Gudmundsson, S., & Jensen, P. E. (2017). Responses of Synechocystis sp. PCC 6803 to heterologous biosynthetic pathways. Microbial Cell Factories, 16(1), [140]. https://doi.org/10.1186/s12934-017-0757-y

Vancouver

Vavitsas K, Rue EØ, Stefánsdóttir LK, Gnanasekaran T, Blennow A, Crocoll C o.a. Responses of Synechocystis sp. PCC 6803 to heterologous biosynthetic pathways. Microbial Cell Factories. 2017;16(1). 140. https://doi.org/10.1186/s12934-017-0757-y

Author

Vavitsas, Konstantinos ; Rue, Emil Østergaard ; Stefánsdóttir, Lára Kristín ; Gnanasekaran, Thiyagarajan ; Blennow, Andreas ; Crocoll, Christoph ; Gudmundsson, Steinn ; Jensen, Poul Erik. / Responses of Synechocystis sp. PCC 6803 to heterologous biosynthetic pathways. I: Microbial Cell Factories. 2017 ; Bind 16, Nr. 1.

Bibtex

@article{02000bcb2506480dbba8362e29a0e1a8,
title = "Responses of Synechocystis sp. PCC 6803 to heterologous biosynthetic pathways",
abstract = "BACKGROUND: There are an increasing number of studies regarding genetic manipulation of cyanobacteria to produce commercially interesting compounds. The majority of these works study the expression and optimization of a selected heterologous pathway, largely ignoring the wholeness and complexity of cellular metabolism. Regulation and response mechanisms are largely unknown, and even the metabolic pathways themselves are not fully elucidated. This poses a clear limitation in exploiting the rich biosynthetic potential of cyanobacteria.RESULTS: In this work, we focused on the production of two different compounds, the cyanogenic glucoside dhurrin and the diterpenoid 13R-manoyl oxide in Synechocystis PCC 6803. We used genome-scale metabolic modelling to study fluxes in individual reactions and pathways, and we determined the concentrations of key metabolites, such as amino acids, carotenoids, and chlorophylls. This allowed us to identify metabolic crosstalk between the native and the introduced metabolic pathways. Most results and simulations highlight the metabolic robustness of cyanobacteria, suggesting that the host organism tends to keep metabolic fluxes and metabolite concentrations steady, counteracting the effects of the heterologous pathway. However, the amino acid concentrations of the dhurrin-producing strain show an unexpected profile, where the perturbation levels were high in seemingly unrelated metabolites.CONCLUSIONS: There is a wealth of information that can be derived by combining targeted metabolite identification and computer modelling as a frame of understanding. Here we present an example of how strain engineering approaches can be coupled to 'traditional' metabolic engineering with systems biology, resulting in novel and more efficient manipulation strategies.",
keywords = "Journal Article",
author = "Konstantinos Vavitsas and Rue, {Emil {\O}stergaard} and Stef{\'a}nsd{\'o}ttir, {L{\'a}ra Krist{\'i}n} and Thiyagarajan Gnanasekaran and Andreas Blennow and Christoph Crocoll and Steinn Gudmundsson and Jensen, {Poul Erik}",
year = "2017",
doi = "10.1186/s12934-017-0757-y",
language = "English",
volume = "16",
journal = "Microbial Cell Factories",
issn = "1475-2859",
publisher = "BioMed Central",
number = "1",

}

RIS

TY - JOUR

T1 - Responses of Synechocystis sp. PCC 6803 to heterologous biosynthetic pathways

AU - Vavitsas, Konstantinos

AU - Rue, Emil Østergaard

AU - Stefánsdóttir, Lára Kristín

AU - Gnanasekaran, Thiyagarajan

AU - Blennow, Andreas

AU - Crocoll, Christoph

AU - Gudmundsson, Steinn

AU - Jensen, Poul Erik

PY - 2017

Y1 - 2017

N2 - BACKGROUND: There are an increasing number of studies regarding genetic manipulation of cyanobacteria to produce commercially interesting compounds. The majority of these works study the expression and optimization of a selected heterologous pathway, largely ignoring the wholeness and complexity of cellular metabolism. Regulation and response mechanisms are largely unknown, and even the metabolic pathways themselves are not fully elucidated. This poses a clear limitation in exploiting the rich biosynthetic potential of cyanobacteria.RESULTS: In this work, we focused on the production of two different compounds, the cyanogenic glucoside dhurrin and the diterpenoid 13R-manoyl oxide in Synechocystis PCC 6803. We used genome-scale metabolic modelling to study fluxes in individual reactions and pathways, and we determined the concentrations of key metabolites, such as amino acids, carotenoids, and chlorophylls. This allowed us to identify metabolic crosstalk between the native and the introduced metabolic pathways. Most results and simulations highlight the metabolic robustness of cyanobacteria, suggesting that the host organism tends to keep metabolic fluxes and metabolite concentrations steady, counteracting the effects of the heterologous pathway. However, the amino acid concentrations of the dhurrin-producing strain show an unexpected profile, where the perturbation levels were high in seemingly unrelated metabolites.CONCLUSIONS: There is a wealth of information that can be derived by combining targeted metabolite identification and computer modelling as a frame of understanding. Here we present an example of how strain engineering approaches can be coupled to 'traditional' metabolic engineering with systems biology, resulting in novel and more efficient manipulation strategies.

AB - BACKGROUND: There are an increasing number of studies regarding genetic manipulation of cyanobacteria to produce commercially interesting compounds. The majority of these works study the expression and optimization of a selected heterologous pathway, largely ignoring the wholeness and complexity of cellular metabolism. Regulation and response mechanisms are largely unknown, and even the metabolic pathways themselves are not fully elucidated. This poses a clear limitation in exploiting the rich biosynthetic potential of cyanobacteria.RESULTS: In this work, we focused on the production of two different compounds, the cyanogenic glucoside dhurrin and the diterpenoid 13R-manoyl oxide in Synechocystis PCC 6803. We used genome-scale metabolic modelling to study fluxes in individual reactions and pathways, and we determined the concentrations of key metabolites, such as amino acids, carotenoids, and chlorophylls. This allowed us to identify metabolic crosstalk between the native and the introduced metabolic pathways. Most results and simulations highlight the metabolic robustness of cyanobacteria, suggesting that the host organism tends to keep metabolic fluxes and metabolite concentrations steady, counteracting the effects of the heterologous pathway. However, the amino acid concentrations of the dhurrin-producing strain show an unexpected profile, where the perturbation levels were high in seemingly unrelated metabolites.CONCLUSIONS: There is a wealth of information that can be derived by combining targeted metabolite identification and computer modelling as a frame of understanding. Here we present an example of how strain engineering approaches can be coupled to 'traditional' metabolic engineering with systems biology, resulting in novel and more efficient manipulation strategies.

KW - Journal Article

U2 - 10.1186/s12934-017-0757-y

DO - 10.1186/s12934-017-0757-y

M3 - Journal article

C2 - 28806958

VL - 16

JO - Microbial Cell Factories

JF - Microbial Cell Factories

SN - 1475-2859

IS - 1

M1 - 140

ER -

ID: 182506938