Induced effect of Ca(2+) and Al(3+) on chaetominine synthesis by Aspergillus fumigatus CY018 under submerged fermentation
Biotechnol Appl Biochem. 2022 Jan 7. doi: 10.1002/bab.2318. Online ahead of print.
Chaetominine (CHA), an alkaloid with biological activity form Aspergillus fumigatus CY018, has strong anticancer activity against the human leukemia cell. However, its further physiological and biochemical research is limited by CHA yield in liquid stated fermentation, which is a problem urgently awaiting solutions by effective biological strategies. In this work, Ca2+ and Al3+ were found which possessed a strong promoting effect on CHA production after multiple metal ions screening. Then, the addition condition of Ca2+ and Al3+ was respectively optimized on CHA production and DCW. The intermediate metabolites were increased obviously with co-addition of Ca2+ and Al3+ . The activities of key enzymes of DAHPs, AroAs and TrpCs in CHA biosynthesis pathway were improved by 3.58-, 3.60- and 3.34-folds respectively. Meanwhile, the transcription levels of laeA, dahp, cs, and trpC were up-regulated by 3.22-, 12.65-, 5.58- and 6.99-fold respectively by co-addition of Ca2+ and Al3+ . Additionally, the fermentation strategy was successfully scaled up to 5 L bioreactor, in which CHA production could attain 75.6 mg/L at 336 h. This work demonstrated that Ca2+ and Al3+ co-addition was an effective strategy for increasing CHA production, and the information obtained might be useful to fermentation of filamentous fungi with addition of metal ions. This article is protected by copyright. All rights reserved.