Medium optimization for pyrroloquinoline quinone (PQQ) production by Methylobacillus sp. zju323 using response surface methodology and artificial neural network–genetic algorithm

ABSTRACT

Methylobacillus sp. zju323 was adopted to improve the biosynthesis of pyrroloquinoline quinone (PQQ) by systematic optimization of the fermentation medium. The Plackett–Burman design was implemented to screen for the key medium components for the PQQ production. CoCl₂ · 6H₂O, ρ-amino benzoic acid, and MgSO₄ · 7H₂O were found capable of enhancing the PQQ production most significantly. A five-level three-factor central composite design was used to investigate the direct and interactive effects of these variables. Both response surface methodology (RSM) and artificial neural network–genetic algorithm (ANN–GA) were used to predict the PQQ production and to optimize the medium composition. The results showed that the medium optimized by ANN–GA was better than that by RSM in maximizing PQQ production and the experimental PQQ concentration in the ANN–GA-optimized medium was improved by 44.3% compared with that in the unoptimized medium. Further study showed that this ANN–GA-optimized medium was also effective in improving PQQ production by fed-batch mode, reaching the highest PQQ accumulation of 232.0 mg/L, which was about 47.6% increase relative to that in the original medium. The present work provided an optimized medium and developed a fed-batch strategy which might be potentially applicable in industrial PQQ production.

KEYWORDS:

• Artificial neural network
• fermentation
• genetic algorithm
• pyrroloquinoline quinone
• response surface methodology

Abbreviations:

• AAD, average absolute deviation
• Adj R², adjusted coefficient of determination
• ANN, artificial neural network
• ANOVA, analysis of variance
• AOMM, ANN-optimized methanol medium
• BP, back propagation
• CCD, central composite design
• C.V., coefficient of variation
• DO, dissolved oxygen
• GA, genetic algorithm
• LM, Levenberg–Marquardt
• MLP, multilayered perceptron
• OMM, original methanol medium
• PABA, ρ-amino benzoic acid
• PBD, Plackett–Burman design
• PQQ, pyrroloquinoline quinone
• Pred R², predicted coefficient of determination
• RP, resilient back propagation
• RMSE, root mean square error
• RSM, response surface methodology
• R², coefficient of determination
• SA, steepest ascent
• SCG, scaled conjugate gradient