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Trans-4-hydroxy-L-proline production by the cyanobacterium Synechocystis sp. PCC 6803

Cyanobacteria play an important role in photobiotechnology. Yet, one of their key central metabolic pathways, the tricarboxylic acid (TCA) cycle, has a unique architecture compared to most heterotrophs and still remains largely unexploited. The conversion of 2-oxoglutarate to succinate via succinyl-...

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Autores principales: Brandenburg, Fabian, Theodosiou, Eleni, Bertelmann, Carolin, Grund, Marcel, Klähn, Stephan, Schmid, Andreas, Krömer, Jens O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815826/
https://www.ncbi.nlm.nih.gov/pubmed/33511031
http://dx.doi.org/10.1016/j.mec.2020.e00155
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author Brandenburg, Fabian
Theodosiou, Eleni
Bertelmann, Carolin
Grund, Marcel
Klähn, Stephan
Schmid, Andreas
Krömer, Jens O.
author_facet Brandenburg, Fabian
Theodosiou, Eleni
Bertelmann, Carolin
Grund, Marcel
Klähn, Stephan
Schmid, Andreas
Krömer, Jens O.
author_sort Brandenburg, Fabian
collection PubMed
description Cyanobacteria play an important role in photobiotechnology. Yet, one of their key central metabolic pathways, the tricarboxylic acid (TCA) cycle, has a unique architecture compared to most heterotrophs and still remains largely unexploited. The conversion of 2-oxoglutarate to succinate via succinyl-CoA is absent but is by-passed by several other reactions. Overall, fluxes under photoautotrophic growth conditions through the TCA cycle are low, which has implications for the production of chemicals. In this study, we investigate the capacity of the TCA cycle of Synechocystis sp PCC 6803 for the production of trans-4-hydroxy-L-proline (Hyp), a valuable chiral building block for the pharmaceutical and cosmetic industries. For the first time, photoautotrophic Hyp production was achieved in a cyanobacterium expressing the gene for the L-proline-4-hydroxylase (P4H) from Dactylosporangium sp. strain RH1. Interestingly, while elevated intracellular Hyp concentrations could be detected in the recombinant Synechocystis strains under all tested conditions, detectable Hyp secretion into the medium was only observed when the pH of the medium exceeded 9.5 and mostly in the late phases of the cultivation. We compared the rates obtained for autotrophic Hyp production with published sugar-based production rates in E. coli. The land-use efficiency (space-time yield) of the phototrophic process is already in the same order of magnitude as the heterotrophic process considering sugar farming as well. But, the remarkable plasticity of the cyanobacterial TCA cycle promises the potential for a 23–55 fold increase in space-time yield when using Synechocystis. Altogether, these findings contribute to a better understanding of bioproduction from the TCA cycle in photoautotrophs and broaden the spectrum of chemicals produced in metabolically engineered cyanobacteria.
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spelling pubmed-78158262021-01-27 Trans-4-hydroxy-L-proline production by the cyanobacterium Synechocystis sp. PCC 6803 Brandenburg, Fabian Theodosiou, Eleni Bertelmann, Carolin Grund, Marcel Klähn, Stephan Schmid, Andreas Krömer, Jens O. Metab Eng Commun Special issue on Engineering Cyanobacteria edited by Peter Lindblad and Jens Krömer Cyanobacteria play an important role in photobiotechnology. Yet, one of their key central metabolic pathways, the tricarboxylic acid (TCA) cycle, has a unique architecture compared to most heterotrophs and still remains largely unexploited. The conversion of 2-oxoglutarate to succinate via succinyl-CoA is absent but is by-passed by several other reactions. Overall, fluxes under photoautotrophic growth conditions through the TCA cycle are low, which has implications for the production of chemicals. In this study, we investigate the capacity of the TCA cycle of Synechocystis sp PCC 6803 for the production of trans-4-hydroxy-L-proline (Hyp), a valuable chiral building block for the pharmaceutical and cosmetic industries. For the first time, photoautotrophic Hyp production was achieved in a cyanobacterium expressing the gene for the L-proline-4-hydroxylase (P4H) from Dactylosporangium sp. strain RH1. Interestingly, while elevated intracellular Hyp concentrations could be detected in the recombinant Synechocystis strains under all tested conditions, detectable Hyp secretion into the medium was only observed when the pH of the medium exceeded 9.5 and mostly in the late phases of the cultivation. We compared the rates obtained for autotrophic Hyp production with published sugar-based production rates in E. coli. The land-use efficiency (space-time yield) of the phototrophic process is already in the same order of magnitude as the heterotrophic process considering sugar farming as well. But, the remarkable plasticity of the cyanobacterial TCA cycle promises the potential for a 23–55 fold increase in space-time yield when using Synechocystis. Altogether, these findings contribute to a better understanding of bioproduction from the TCA cycle in photoautotrophs and broaden the spectrum of chemicals produced in metabolically engineered cyanobacteria. Elsevier 2020-12-31 /pmc/articles/PMC7815826/ /pubmed/33511031 http://dx.doi.org/10.1016/j.mec.2020.e00155 Text en © 2020 Published by Elsevier B.V. on behalf of International Metabolic Engineering Society. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Special issue on Engineering Cyanobacteria edited by Peter Lindblad and Jens Krömer
Brandenburg, Fabian
Theodosiou, Eleni
Bertelmann, Carolin
Grund, Marcel
Klähn, Stephan
Schmid, Andreas
Krömer, Jens O.
Trans-4-hydroxy-L-proline production by the cyanobacterium Synechocystis sp. PCC 6803
title Trans-4-hydroxy-L-proline production by the cyanobacterium Synechocystis sp. PCC 6803
title_full Trans-4-hydroxy-L-proline production by the cyanobacterium Synechocystis sp. PCC 6803
title_fullStr Trans-4-hydroxy-L-proline production by the cyanobacterium Synechocystis sp. PCC 6803
title_full_unstemmed Trans-4-hydroxy-L-proline production by the cyanobacterium Synechocystis sp. PCC 6803
title_short Trans-4-hydroxy-L-proline production by the cyanobacterium Synechocystis sp. PCC 6803
title_sort trans-4-hydroxy-l-proline production by the cyanobacterium synechocystis sp. pcc 6803
topic Special issue on Engineering Cyanobacteria edited by Peter Lindblad and Jens Krömer
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815826/
https://www.ncbi.nlm.nih.gov/pubmed/33511031
http://dx.doi.org/10.1016/j.mec.2020.e00155
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