Medium optimization for enhanced co-production of two bioactive metabolites in the same fermentation by a statistical approach.

This paper describes improved optimization method that combines the one-factor-at-a-time method (OFAT), Plackett-Burman design, and the response surface method (RSM), which were used to optimize the medium for the production of fumigaclavine C (FC) and helvolic acid (HA) from endophytic Aspergillus fumigatus CY018 simultaneously. The ideal carbon and nitrogen sources for the two compounds were assessed initially via the one-factor-at-a-time method. Three key cultivation factors (pH, phosphate, and inoculum size) were chosen based on the results of Plackett-Burman design, and subsequently optimized by the central composite design. The two metabolites were amply afforded when the cultivation was carried out with the inoculum size of 2.45% at pH 4.2 and 28°C for 19 days in the medium containing (g/l): mannitol 50, sodium succinate 5.4, NaNO₃ 2, MgSO₄·7H₂O 0.3, FeSO₄·7H₂O 0.01, and KH₂PO₄ 0.67. The highest yields of FC and HA achieved herein were 17.26 and 16.88 mg/l. This work might be the first endeavor leading to the improved simultaneous production of two complex active metabolites with a single strain.