title: Mn(2+) and Mg(2+) synergistically enhanced lactic acid production by Lactobacillus rhamnosus FTDC 8313 via affecting different stages of the hexose monophosphate pathway.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Industrial Technology, Universiti Sains Malaysia, Penang, Malaysia.
authors.forename: L-C
authors.initials: LC
authors.lastname: Lew
authors.forename: S-B
authors.initials: SB
authors.lastname: Choi
authors.forename: P-L
authors.initials: PL
authors.lastname: Tan
authors.forename: M-T
authors.initials: MT
authors.lastname: Liong
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D002413:Cations, Divalent; D019344:Lactic Acid / Q000096:biosynthesis*; D052201:Lacticaseibacillus rhamnosus / Q000187:drug effects / Q000201:enzymology*; D008278:Magnesium Sulfate / Q000494:pharmacology*; D017895:Manganese Compounds / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D010427:Pentose Phosphate Pathway / Q000187:drug effects; D013431:Sulfates / Q000494:pharmacology*
chemical_list: D001426:Bacterial Proteins; D002413:Cations, Divalent; D017895:Manganese Compounds; D013431:Sulfates; D019344:Lactic Acid; D008278:Magnesium Sulfate; C039798:manganese sulfate
keywords: Lactobacillus; biotechnology; modelling; probiotics