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Combination of Plant Metabolic Modules Yields Synthetic Synergies

The great potential of pharmacologically active secondary plant metabolites is often limited by low yield and availability of the producing plant. Chemical synthesis of these complex compounds is often too expensive. Plant cell fermentation offers an alternative strategy to overcome these limitation...

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Autores principales: Rajabi, Fatemeh, Heene, Ernst, Maisch, Jan, Nick, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5231347/
https://www.ncbi.nlm.nih.gov/pubmed/28081182
http://dx.doi.org/10.1371/journal.pone.0169778
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author Rajabi, Fatemeh
Heene, Ernst
Maisch, Jan
Nick, Peter
author_facet Rajabi, Fatemeh
Heene, Ernst
Maisch, Jan
Nick, Peter
author_sort Rajabi, Fatemeh
collection PubMed
description The great potential of pharmacologically active secondary plant metabolites is often limited by low yield and availability of the producing plant. Chemical synthesis of these complex compounds is often too expensive. Plant cell fermentation offers an alternative strategy to overcome these limitations. However, production in batch cell cultures remains often inefficient. One reason might be the fact that different cell types have to interact for metabolite maturation, which is poorly mimicked in suspension cell lines. Using alkaloid metabolism of tobacco, we explore an alternative strategy, where the metabolic interactions of different cell types in a plant tissue are technically mimicked based on different plant-cell based metabolic modules. In this study, we simulate the interaction found between the nicotine secreting cells of the root and the nicotine-converting cells of the senescent leaf, generating the target compound nornicotine in the model cell line tobacco BY-2. When the nicotine demethylase NtomCYP82E4 was overexpressed in tobacco BY-2 cells, nornicotine synthesis was triggered, but only to a minor extent. However, we show here that we can improve the production of nornicotine in this cell line by feeding the precursor, nicotine. Engineering of another cell line overexpressing the key enzyme NtabMPO1 allows to stimulate accumulation and secretion of this precursor. We show that the nornicotine production of NtomCYP82E4 cells can be significantly stimulated by feeding conditioned medium from NtabMPO1 overexpressors without any negative effect on the physiology of the cells. Co-cultivation of NtomCYP82E4 with NtabMPO1 stimulated nornicotine accumulation even further, demonstrating that the physical presence of cells was superior to just feeding the conditioned medium collected from the same cells. These results provide a proof of concept that combination of different metabolic modules can improve the productivity for target compounds in plant cell fermentation.
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spelling pubmed-52313472017-01-31 Combination of Plant Metabolic Modules Yields Synthetic Synergies Rajabi, Fatemeh Heene, Ernst Maisch, Jan Nick, Peter PLoS One Research Article The great potential of pharmacologically active secondary plant metabolites is often limited by low yield and availability of the producing plant. Chemical synthesis of these complex compounds is often too expensive. Plant cell fermentation offers an alternative strategy to overcome these limitations. However, production in batch cell cultures remains often inefficient. One reason might be the fact that different cell types have to interact for metabolite maturation, which is poorly mimicked in suspension cell lines. Using alkaloid metabolism of tobacco, we explore an alternative strategy, where the metabolic interactions of different cell types in a plant tissue are technically mimicked based on different plant-cell based metabolic modules. In this study, we simulate the interaction found between the nicotine secreting cells of the root and the nicotine-converting cells of the senescent leaf, generating the target compound nornicotine in the model cell line tobacco BY-2. When the nicotine demethylase NtomCYP82E4 was overexpressed in tobacco BY-2 cells, nornicotine synthesis was triggered, but only to a minor extent. However, we show here that we can improve the production of nornicotine in this cell line by feeding the precursor, nicotine. Engineering of another cell line overexpressing the key enzyme NtabMPO1 allows to stimulate accumulation and secretion of this precursor. We show that the nornicotine production of NtomCYP82E4 cells can be significantly stimulated by feeding conditioned medium from NtabMPO1 overexpressors without any negative effect on the physiology of the cells. Co-cultivation of NtomCYP82E4 with NtabMPO1 stimulated nornicotine accumulation even further, demonstrating that the physical presence of cells was superior to just feeding the conditioned medium collected from the same cells. These results provide a proof of concept that combination of different metabolic modules can improve the productivity for target compounds in plant cell fermentation. Public Library of Science 2017-01-12 /pmc/articles/PMC5231347/ /pubmed/28081182 http://dx.doi.org/10.1371/journal.pone.0169778 Text en © 2017 Rajabi et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Rajabi, Fatemeh
Heene, Ernst
Maisch, Jan
Nick, Peter
Combination of Plant Metabolic Modules Yields Synthetic Synergies
title Combination of Plant Metabolic Modules Yields Synthetic Synergies
title_full Combination of Plant Metabolic Modules Yields Synthetic Synergies
title_fullStr Combination of Plant Metabolic Modules Yields Synthetic Synergies
title_full_unstemmed Combination of Plant Metabolic Modules Yields Synthetic Synergies
title_short Combination of Plant Metabolic Modules Yields Synthetic Synergies
title_sort combination of plant metabolic modules yields synthetic synergies
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5231347/
https://www.ncbi.nlm.nih.gov/pubmed/28081182
http://dx.doi.org/10.1371/journal.pone.0169778
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