Induced effect of Ca2+ and Al3+ on chaetominine synthesis by Aspergillus fumigatus CY018 under submerged fermentation

Abstract

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, Ca²⁺ and Al³⁺ were found to have a strong promoting effect on CHA production after multiple metal ions screening. Then, the addition condition of Ca²⁺ and Al³⁺ was, respectively, optimized CHA production and dry cell weight. The intermediate metabolites were increased with coaddition of Ca²⁺ and Al³⁺ . 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 Ca²⁺ and Al³⁺ . 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 Ca²⁺ and Al³⁺ 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.

Keywords: Aspergillus fumigatus; aluminum ion; calcium ion; chaetominine; submerged fermentation.