Induced effect of Ca 2+ and Al 3+ on chaetominine synthesis by Aspergillus fumigatus CY018 under submerged fermentation

Chaetominine (CHA), an alkaloid with a biological activity obtained from Aspergillus fumigatus CY018, has strong anticancer activity against the human leukemia cells. However, its physiological and biochemical research is limited by CHA yield in the liquid-state fermentation, which is a problem that urgently needs effective biological solution. In this work, Ca and Al were found to have a strong promoting effect on CHA production after multiple metal ions screening. Then, the addition condition of Ca and Al was, respectively, optimized CHA production and dry cell weight. The intermediate metabolites were increased with coaddition of Ca and Al . The activities of key enzymes of DAHPs, AroAs, and TrpCs in the CHA biosynthesis pathway were improved by 3.58-, 3.60-, and 3.34-fold, respectively. Meanwhile, the transcription level of laeA, dahp, cs, and trpC was upregulated by 3.22-, 12.65-, 5.58-, and 6.99-fold, respectively, by coaddition of Ca and Al . Additionally, the fermentation strategy was successfully scaled up to a 5-L bioreactor, in which CHA production could attain 75.6 mg/L at 336 h. This work demonstrated that Ca and Al coaddition was an effective strategy for increasing CHA production, and the information obtained might be useful in the fermentation of filamentous fungi with the addition of metal ions.