Abstract

Plackett-Burman design and response surface methodology were applied in order to optimize the fermentation medium of (R)-α-hydroxyphenylacetic acid ((R)-HPA) producing Bacillus sp. HZG-19. The factors playing important roles in the production of (R)-HPA were selected based on Plackett-Burman design. The path of steepest ascent was undertaken to optimize said fermentation medium. Finally, the optimal levels of the factors with the greatest change in regard to product yield were further optimized using Box-Behnken and response surface analysis. The optimal conditions were found to be as follows: casein peptone 30.49 (g × L-1), glycerol 14.09 (g × L-1), KH2PO4 0.1345 (g × L-1), K2HPO4 0.01 (g × L-1), CaCl2 0.1 (g × L-1), MnSO4 0.01 (g × L-1). Under the optimal conditions described above, the yield of (R)-HPA reached 63.30%, which indicated an increase of 14.9%, as compared to the yield obtained before optimization.

Highlights

  • Introduction αHydroxyphenylacetic acid (HPA) and its derivatives are key intermediates for the production of various pharmaceuticals, such as semi-synthetic penicillins and cephalosporins [1,2,3]

  • Plackett-Burman design and response surface methodology were applied in order to optimize the fermentation medium of (R)-α-hydroxyphenylacetic acid ((R)-HPA) producing Bacillus sp

  • Under the optimal conditions described above, the yield of (R)-HPA reached 63.30%, which indicated an increase of 14.9%, as compared to the yield obtained before optimization

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Summary

Strain and Chemicals

HZG-19) was preserved in the lab of Chemical Engineering Department, Fuzhou University. (R)-HPA and (S)-HPA were purchased from Sigma (St. Louis, MO USA). Phenylglyoxylic acid (PGA, >98%) was supplied by Pharmaceutical & Chemical Co., Ltd of Taizhou, China. Methyl alcohol of HPLC grade was purchased from Merck, Germany. Β-cyclodextrin (HP-β-CD) was supplied by Fluka (Neu Ulm, Germany). All other chemicals were obtained from local suppliers and of reagent grade

Medium
Culture Conditions
Analytical Methods
Plackett-Burman Design
Steepest Ascent Design to Approach the Optimal Region
Conclusion

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