ArticleMicrobial cell factories2015
Integrated isotope-assisted metabolomics and (13)C metabolic flux analysis reveals metabolic flux redistribution for high glucoamylase production by Aspergillus niger.
Article in Microbial cell factories, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 45 citations in OpenAlex.
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- Mechanistic insight for improving butenyl-spinosyn production through combined ARTP/UV mutagenesis and ribosome engineering inFrontiers in bioengineering and biotechnology · 2023Article
- Impact of overexpressing NADH kinase on glucoamylase production in Aspergillus niger.Journal of industrial microbiology & biotechnology · 2022Article
- Linear programming based gene expression model (LPM-GEM) predicts the carbon source for Bacillus subtilis.BMC bioinformatics · 2022Article
- Assessing the intracellular primary metabolic profile ofFrontiers in fungal biology · 2022Article
- Integration of enzyme constraints in a genome-scale metabolic model of Aspergillus niger improves phenotype predictions.Microbial cell factories · 2021Article
- Engineering cofactor metabolism for improved protein and glucoamylase production in Aspergillus niger.Microbial cell factories · 2020Article
- Systems metabolic engineering for citric acid production by Aspergillus niger in the post-genomic era.Microbial cell factories · 2019Review
- Functional exploration of co-expression networks identifies a nexus for modulating protein and citric acid titres inFungal biology and biotechnology · 2019Article
- Transcriptomic and fluxomic changes in Streptomyces lividans producing heterologous protein.Microbial cell factories · 2018Article
- Multi-omics integrative analysis with genome-scale metabolic model simulation reveals global cellular adaptation of Aspergillus niger under industrial enzyme production condition.Scientific reports · 2018Article
- Targeted redox and energy cofactor metabolomics inBiotechnology for biofuels · 2017Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
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Abstract
backgroundAspergillus niger is widely used for enzyme production and achievement of high enzyme production depends on the comprehensive understanding of cell's metabolic regulation mechanisms.
resultsIn 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.
conclusionsThe 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. Graphical abstract An integrated isotope-assisted metabolomics and (13)C metabolic flux analysis was was firstly systematically performed in A. niger. In response to enzyme production, the metabolic flux in A. niger DS03043 (high-producing) was redistributed, characterized by an increased carbon flux directed to the oxidative pentose phosphate pathway as well as an increased pool size of pentose. The consistency in (13)C metabolic flux analysis and metabolites quantification indicated that an imbalance of NADH formation and consumption led to the accumulation and secretion of organic acids in A. niger CBS513.88 (wild-type).
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