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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 .   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)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.

microbial cell factories

Integrated isotope-assisted metabolomics and 13C metabolic flux analysis reveals metabolic flux redistribution for high glucoamylase production by Aspergillus niger