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Enhanced itaconic acid production in Aspergillus niger using genetic modification and medium optimization

BACKGROUND: Aspergillus niger was selected as a host for producing itaconic acid due to its versatile and tolerant character in various growth environments, and its extremely high capacity of accumulating the precursor of itaconic acid: citric acid. Expressing the CAD gene from Aspergillus terreus o...

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Autores principales: Li, An, Pfelzer, Nina, Zuijderwijk, Robbert, Punt, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472327/
https://www.ncbi.nlm.nih.gov/pubmed/22925689
http://dx.doi.org/10.1186/1472-6750-12-57
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author Li, An
Pfelzer, Nina
Zuijderwijk, Robbert
Punt, Peter
author_facet Li, An
Pfelzer, Nina
Zuijderwijk, Robbert
Punt, Peter
author_sort Li, An
collection PubMed
description BACKGROUND: Aspergillus niger was selected as a host for producing itaconic acid due to its versatile and tolerant character in various growth environments, and its extremely high capacity of accumulating the precursor of itaconic acid: citric acid. Expressing the CAD gene from Aspergillus terreus opened the metabolic pathway towards itaconic acid in A. niger. In order to increase the production level, we continued by modifying its genome and optimizing cultivation media. RESULTS: Based on the results of previous transcriptomics studies and research from other groups, two genes : gpdA encoding the glyceraldehyde −3-dehydrogenase (GPD) and hbd1 encoding a flavohemoglobin domain (HBD) were overexpressed in A. niger. Besides, new media were designed based on a reference medium for A. terreus. To analyze large numbers of cultures, we developed an approach for screening both fungal transformants and various media in 96-well micro-titer plates. The hbd1 transformants (HBD 2.2/2.5) did not improve itaconic acid titer while the gpdA transformant (GPD 4.3) decreased the itaconic acid production. Using 20 different media, copper was discovered to have a positive influence on itaconic acid production. Effects observed in the micro-titer plate screening were confirmed in controlled batch fermentation. CONCLUSIONS: The performance of gpdA and hbd1 transformants was found not to be beneficial for itaconic acid production using the tested cultivation conditions. Medium optimization showed that, copper was positively correlated with improved itaconic acid production. Interestingly, the optimal conditions for itaconic acid clearly differ from conditions optimal for citric- and oxalic acid production.
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spelling pubmed-34723272012-10-17 Enhanced itaconic acid production in Aspergillus niger using genetic modification and medium optimization Li, An Pfelzer, Nina Zuijderwijk, Robbert Punt, Peter BMC Biotechnol Research Article BACKGROUND: Aspergillus niger was selected as a host for producing itaconic acid due to its versatile and tolerant character in various growth environments, and its extremely high capacity of accumulating the precursor of itaconic acid: citric acid. Expressing the CAD gene from Aspergillus terreus opened the metabolic pathway towards itaconic acid in A. niger. In order to increase the production level, we continued by modifying its genome and optimizing cultivation media. RESULTS: Based on the results of previous transcriptomics studies and research from other groups, two genes : gpdA encoding the glyceraldehyde −3-dehydrogenase (GPD) and hbd1 encoding a flavohemoglobin domain (HBD) were overexpressed in A. niger. Besides, new media were designed based on a reference medium for A. terreus. To analyze large numbers of cultures, we developed an approach for screening both fungal transformants and various media in 96-well micro-titer plates. The hbd1 transformants (HBD 2.2/2.5) did not improve itaconic acid titer while the gpdA transformant (GPD 4.3) decreased the itaconic acid production. Using 20 different media, copper was discovered to have a positive influence on itaconic acid production. Effects observed in the micro-titer plate screening were confirmed in controlled batch fermentation. CONCLUSIONS: The performance of gpdA and hbd1 transformants was found not to be beneficial for itaconic acid production using the tested cultivation conditions. Medium optimization showed that, copper was positively correlated with improved itaconic acid production. Interestingly, the optimal conditions for itaconic acid clearly differ from conditions optimal for citric- and oxalic acid production. BioMed Central 2012-08-27 /pmc/articles/PMC3472327/ /pubmed/22925689 http://dx.doi.org/10.1186/1472-6750-12-57 Text en Copyright ©2012 Li et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Li, An
Pfelzer, Nina
Zuijderwijk, Robbert
Punt, Peter
Enhanced itaconic acid production in Aspergillus niger using genetic modification and medium optimization
title Enhanced itaconic acid production in Aspergillus niger using genetic modification and medium optimization
title_full Enhanced itaconic acid production in Aspergillus niger using genetic modification and medium optimization
title_fullStr Enhanced itaconic acid production in Aspergillus niger using genetic modification and medium optimization
title_full_unstemmed Enhanced itaconic acid production in Aspergillus niger using genetic modification and medium optimization
title_short Enhanced itaconic acid production in Aspergillus niger using genetic modification and medium optimization
title_sort enhanced itaconic acid production in aspergillus niger using genetic modification and medium optimization
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472327/
https://www.ncbi.nlm.nih.gov/pubmed/22925689
http://dx.doi.org/10.1186/1472-6750-12-57
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