Abstract
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.
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