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Integrated isotope-assisted metabolomics and (13)C metabolic flux analysis reveals metabolic flux redistribution for high glucoamylase production by Aspergillus niger
BACKGROUND: Aspergillus niger is widely used for enzyme production and achievement of high enzyme production depends on the comprehensive understanding of cell’s metabolic regulation mechanisms. RESULTS: In this paper, we investigate the metabolic differences and regulation mechanisms between a high...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574132/ https://www.ncbi.nlm.nih.gov/pubmed/26383080 http://dx.doi.org/10.1186/s12934-015-0329-y |
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author | Lu, Hongzhong Liu, Xiaoyun Huang, Mingzhi Xia, Jianye Chu, Ju Zhuang, Yingping Zhang, Siliang Noorman, Henk |
author_facet | Lu, Hongzhong Liu, Xiaoyun Huang, Mingzhi Xia, Jianye Chu, Ju Zhuang, Yingping Zhang, Siliang Noorman, Henk |
author_sort | Lu, Hongzhong |
collection | PubMed |
description | BACKGROUND: Aspergillus niger is widely used for enzyme production and achievement of high enzyme production depends on the comprehensive understanding of cell’s metabolic regulation mechanisms. RESULTS: In this paper, we investigate the metabolic differences and regulation mechanisms between a high glucoamylase-producing strain A. niger DS03043 and its wild-type parent strain A. niger CBS513.88 via an integrated isotope-assisted metabolomics and (13)C metabolic flux analysis approach. We found that A. niger DS03043 had higher cell growth, glucose uptake, and glucoamylase production rates but lower oxalic acid and citric acid secretion rates. In response to above phenotype changes, A. niger DS03043 was characterized by an increased carbon flux directed to the oxidative pentose phosphate pathway in contrast to reduced flux through TCA cycle, which were confirmed by consistent changes in pool sizes of metabolites. A higher ratio of ATP over AMP in the high producing strain might contribute to the increase in the PP pathway flux as glucosephosphate isomerase was inhibited at higher ATP concentrations. A. niger CBS513.88, however, was in a higher redox state due to the imbalance of NADH regeneration and consumption, resulting in the secretion of oxalic acid and citric acid, as well as the accumulation of intracellular OAA and PEP, which may in turn result in the decrease in the glucose uptake rate. CONCLUSIONS: The application of integrated metabolomics and (13)C metabolic flux analysis highlights the regulation mechanisms of energy and redox metabolism on flux redistribution in A. niger. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12934-015-0329-y) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4574132 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-45741322015-09-19 Integrated isotope-assisted metabolomics and (13)C metabolic flux analysis reveals metabolic flux redistribution for high glucoamylase production by Aspergillus niger Lu, Hongzhong Liu, Xiaoyun Huang, Mingzhi Xia, Jianye Chu, Ju Zhuang, Yingping Zhang, Siliang Noorman, Henk Microb Cell Fact Research BACKGROUND: Aspergillus niger is widely used for enzyme production and achievement of high enzyme production depends on the comprehensive understanding of cell’s metabolic regulation mechanisms. RESULTS: In this paper, we investigate the metabolic differences and regulation mechanisms between a high glucoamylase-producing strain A. niger DS03043 and its wild-type parent strain A. niger CBS513.88 via an integrated isotope-assisted metabolomics and (13)C metabolic flux analysis approach. We found that A. niger DS03043 had higher cell growth, glucose uptake, and glucoamylase production rates but lower oxalic acid and citric acid secretion rates. In response to above phenotype changes, A. niger DS03043 was characterized by an increased carbon flux directed to the oxidative pentose phosphate pathway in contrast to reduced flux through TCA cycle, which were confirmed by consistent changes in pool sizes of metabolites. A higher ratio of ATP over AMP in the high producing strain might contribute to the increase in the PP pathway flux as glucosephosphate isomerase was inhibited at higher ATP concentrations. A. niger CBS513.88, however, was in a higher redox state due to the imbalance of NADH regeneration and consumption, resulting in the secretion of oxalic acid and citric acid, as well as the accumulation of intracellular OAA and PEP, which may in turn result in the decrease in the glucose uptake rate. CONCLUSIONS: The application of integrated metabolomics and (13)C metabolic flux analysis highlights the regulation mechanisms of energy and redox metabolism on flux redistribution in A. niger. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12934-015-0329-y) contains supplementary material, which is available to authorized users. BioMed Central 2015-09-17 /pmc/articles/PMC4574132/ /pubmed/26383080 http://dx.doi.org/10.1186/s12934-015-0329-y Text en © Lu et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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 Lu, Hongzhong Liu, Xiaoyun Huang, Mingzhi Xia, Jianye Chu, Ju Zhuang, Yingping Zhang, Siliang Noorman, Henk Integrated isotope-assisted metabolomics and (13)C metabolic flux analysis reveals metabolic flux redistribution for high glucoamylase production by Aspergillus niger |
title | Integrated isotope-assisted metabolomics and (13)C metabolic flux analysis reveals metabolic flux redistribution for high glucoamylase production by Aspergillus niger |
title_full | Integrated isotope-assisted metabolomics and (13)C metabolic flux analysis reveals metabolic flux redistribution for high glucoamylase production by Aspergillus niger |
title_fullStr | Integrated isotope-assisted metabolomics and (13)C metabolic flux analysis reveals metabolic flux redistribution for high glucoamylase production by Aspergillus niger |
title_full_unstemmed | Integrated isotope-assisted metabolomics and (13)C metabolic flux analysis reveals metabolic flux redistribution for high glucoamylase production by Aspergillus niger |
title_short | Integrated isotope-assisted metabolomics and (13)C metabolic flux analysis reveals metabolic flux redistribution for high glucoamylase production by Aspergillus niger |
title_sort | integrated isotope-assisted metabolomics and (13)c metabolic flux analysis reveals metabolic flux redistribution for high glucoamylase production by aspergillus niger |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574132/ https://www.ncbi.nlm.nih.gov/pubmed/26383080 http://dx.doi.org/10.1186/s12934-015-0329-y |
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