Induced effect of Ca2+ on curvulamine synthesis by marine-derived fungus Curvularia sp. IFB-Z10 under submerged fermentation

Abstract

Abstract Curvulamine is a novel framework alkaloid with prominent antibacterial and acetylcholinesterase inhibitory activities produced by marine fungus, Curvularia sp. IFB-Z10. However, the low yield severely restricts its further pharmaceutical researches and applications. The study was aimed to enhance curvulamine production based on CaCl2 addition strategy and further clarify the underlying regulation mechanism of Ca2+. In this work, the optimal addition conditions of CaCl2 were firstly obtained, and curvulamine production achieved 42.96 mg/L under supplying 5 mM CaCl2 at 0 h, which was 3.33-fold that of control in shake flask. It was further found that cytosolic Ca2+ level was markedly increased through calcium channel under CaCl2 stimulation. Relatively high intracellular Ca2+ level could induce fungus to principally form pellets with small diameter and compact structure (morphology), and significantly up-regulate the transcriptional and expression levels of key biosynthetic genes, which collectively promoted curvulamine synthesis. Finally, CaCl2 addition strategy was successfully applied in 5-L bioreactor. This work provided an effective regulation strategy to improve curvulamine production in submerged fermentation of Curvularia sp. and it would facilitate further research on the synthesis regulation of secondary metabolites from other marine filamentous fungi.