Ammonium Acetate Supplement Strategy for Enhancement of Chaetominine Production in Liquid Culture of Marine-Derived Aspergillus fumigatus CY018

Abstract

Chaetominine (CHA), a marine-derived quinazolinone alkaloid with significant cytotoxic activity, is restricted by low yields on pharmacological research, which needs to be settled urgently. In this work, the selection of additional nitrogen sources, optimization of the addition concentration and addition time of ammonium acetate, were investigated. CHA production was optimized to 62.1 mg/L with the addition of 50 mM ammonium acetate at 120 h of the fermentation in the shaker flask. This feeding strategy significantly increased 3-deoxy-arabino-heptulosonate-7-phosphate synthase activity and transcript levels of critical genes (laeA, dahp and trpC) in the shikimate pathway compared with the non-treatment group. In addition, the selection of feeding rate (0.01 and 0.03 g/L/h) was investigated in a 5-L bioreactor. And, CHA production was increased 57.9 mg/L with a 0.01 g/L/h ammonium acetate feeding rate. This work showed the strategy of ammonium acetate supplement had an effective role in improving CHA production by Aspergillus fumigatus CY018. This strategy could provide a precious experience for the large-scale fermentation of marine fungus in submerged culture.

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

“…In the previous work, the author explored the biosynthetic path of CHA and found that the key genes significantly affected the biosynthesis of CHA) 16,19 . To further explore the underlying mechanism of coaddition of Ca 2+ and Al 3+ in CHA production, transcription levels of four genes laeA (a global regulator), and dahp , cs , and trpC (CHA biosynthetic pathway) were analyzed by qRT‐PCR.…”

“…The experiments of lab‐scale fermentation process were performed in a 5‐L stirred bioreactor as mentioned by Liu et al., 19 in which was coadded with Ca 2+ and Al 3+ as the optimized concentration for 120 h. Samples were taken at an interval of 48 h.…”

“…In the previous work, the author explored the biosynthetic path of CHA and found that the key genes significantly The addition condition of Ca 2+ and Al 3+ were both 0.5 mM and at 120 h of fermentation time affected the biosynthesis of CHA). 16,19 To further explore the underlying mechanism of coaddition of Ca 2+ and Al 3+ in CHA production, transcription levels of four genes laeA (a global regulator), and dahp, cs, and trpC (CHA biosynthetic pathway) were analyzed by qRT-PCR. The expression levels of these genes with coaddition of Ca 2+ and Al 3+ at 120, 168, 216, 264, 312, and 360 h were sampled and investigated (Figure 6).…”

Natural Indole Alkaloids from Marine Fungi: Chemical Diversity and Biological Activities

“…12 ), a quinazolinone alkaloid produced by marine crab-derived fungus A. fumigatus CY018, showed potent growth-inhibitory activity toward K562 and SW1116 cell lines. 101…”

Untitled

“…12), a quinazolinone alkaloid produced by marine crab-derived fungus A. fumigatus CY018, showed potent growth-inhibitory activity toward K562 and SW1116 cell lines. 101 Neofiscalin A (219) and fiscalin C (220) (►Fig. 12) were two quinazolinone alkaloids obtained from Neosartorya siamensis KUFA 0017, a marine sponge-associated fungus.…”