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Generation of aroE overexpression mutant of Bacillus megaterium for the production of shikimic acid

BACKGROUND: Shikimic acid, the sole chemical building block for the antiviral drug oseltamivir (Tamiflu®), is one of the potent pharmaceutical intermediates with three chiral centers. Here we report a metabolically engineered recombinant Bacillus megaterium strain with aroE (shikimate dehydrogenase)...

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Autores principales: Ghosh, Saptarshi, Banerjee, Uttam Chand
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490670/
https://www.ncbi.nlm.nih.gov/pubmed/25981549
http://dx.doi.org/10.1186/s12934-015-0251-3
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author Ghosh, Saptarshi
Banerjee, Uttam Chand
author_facet Ghosh, Saptarshi
Banerjee, Uttam Chand
author_sort Ghosh, Saptarshi
collection PubMed
description BACKGROUND: Shikimic acid, the sole chemical building block for the antiviral drug oseltamivir (Tamiflu®), is one of the potent pharmaceutical intermediates with three chiral centers. Here we report a metabolically engineered recombinant Bacillus megaterium strain with aroE (shikimate dehydrogenase) overexpression for the production of shikimic acid. RESULTS: In a 7 L bioreactor, 4.2 g/L shikimic acid was obtained using the recombinant strain over 0.53 g/L with the wild type. The enhancement of total shikimate dehydrogenase activity was 2.13-fold higher than the wild type. Maximum yield of shikimic acid (12.54 g/L) was obtained with fructose as carbon source. It was isolated from the fermentation broth using amberlite IRA-400 resin and 89 % purity of the product was achieved. CONCLUSION: This will add up a new organism in the armory for the fermentation based production which is better over plant based extraction and chemical synthesis of shikimic acid. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12934-015-0251-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-44906702015-07-04 Generation of aroE overexpression mutant of Bacillus megaterium for the production of shikimic acid Ghosh, Saptarshi Banerjee, Uttam Chand Microb Cell Fact Research BACKGROUND: Shikimic acid, the sole chemical building block for the antiviral drug oseltamivir (Tamiflu®), is one of the potent pharmaceutical intermediates with three chiral centers. Here we report a metabolically engineered recombinant Bacillus megaterium strain with aroE (shikimate dehydrogenase) overexpression for the production of shikimic acid. RESULTS: In a 7 L bioreactor, 4.2 g/L shikimic acid was obtained using the recombinant strain over 0.53 g/L with the wild type. The enhancement of total shikimate dehydrogenase activity was 2.13-fold higher than the wild type. Maximum yield of shikimic acid (12.54 g/L) was obtained with fructose as carbon source. It was isolated from the fermentation broth using amberlite IRA-400 resin and 89 % purity of the product was achieved. CONCLUSION: This will add up a new organism in the armory for the fermentation based production which is better over plant based extraction and chemical synthesis of shikimic acid. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12934-015-0251-3) contains supplementary material, which is available to authorized users. BioMed Central 2015-05-17 /pmc/articles/PMC4490670/ /pubmed/25981549 http://dx.doi.org/10.1186/s12934-015-0251-3 Text en © Ghosh and Banerjee; licensee BioMed Central. 2015 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 work is properly credited. 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 Research
Ghosh, Saptarshi
Banerjee, Uttam Chand
Generation of aroE overexpression mutant of Bacillus megaterium for the production of shikimic acid
title Generation of aroE overexpression mutant of Bacillus megaterium for the production of shikimic acid
title_full Generation of aroE overexpression mutant of Bacillus megaterium for the production of shikimic acid
title_fullStr Generation of aroE overexpression mutant of Bacillus megaterium for the production of shikimic acid
title_full_unstemmed Generation of aroE overexpression mutant of Bacillus megaterium for the production of shikimic acid
title_short Generation of aroE overexpression mutant of Bacillus megaterium for the production of shikimic acid
title_sort generation of aroe overexpression mutant of bacillus megaterium for the production of shikimic acid
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490670/
https://www.ncbi.nlm.nih.gov/pubmed/25981549
http://dx.doi.org/10.1186/s12934-015-0251-3
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