Mn(2+) and Mg(2+) synergistically enhanced lactic acid production by Lactobacillus rhamnosus FTDC 8313 via affecting different stages of the hexose monophosphate pathway

Aims: The study aimed to evaluate the effects of Mn(2+) and Mg(2+) on lactic acid production using response surface methodology and to further study their effects on interactions between the enzymes and substrates along the hexose monophosphate pathway using a molecular modelling approach.

Methods and results: A rotatable central composite design matrix for lactic acid production was generated with two independent factors namely, manganese sulfate and magnesium sulfate. The second-order regression model indicated that the quadratic model was significant (P < 0·05), suggesting that the model accurately represented the data in the experimental region. Three-dimensional response surface showed that lactic acid production was high along the region where the ratio of MnSO4 to MgSO4 was almost 1 : 1, justifying the need for both Mg(2+) and Mn(2+) to be present simultaneously in stimulating the production of lactic acid. Molecular docking simulation was performed on a total of 13 essential enzymes involved in the hexose monophosphate pathway for the production of lactic acid with four different conditions namely in the presence of Mg(2+) , Mn(2+) , both Mg(2+) and Mn(2+) and in the absence of metal ions. Results showed that the presence of both Mg(2+) and Mn(2+) within the binding site improved the binding affinity for substrates in five enzymes namely, glucose-6-phosphate dehydrogenase, phosphogluconate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, phosphopyruvate hydratase and pyruvate kinase.

Conclusions: Using response surface methodology and molecular modelling approach, we illustrated that Mg(2+) and Mn(2+) synergistically enhanced lactic acid production by Lactobacillus rhamnosus FTDC 8313 via affecting different stages of the hexose monophosphate pathway.

Significance and impacts of the study: Mg(2+) and Mn(2+) synergistically improved lactic acid production of Lact. rhamnosus via improved binding affinity of the enzyme-substrate along the hexose monophosphate pathway, instead of purely affecting growth as previously understood.