Lanthanum elicitation on hypocrellin A production in mycelium cultures of Shiraia bambusicola is mediated by ROS generation

Rare earth elements (REEs) have been widely applied as efficient elicitors to improve production of biologically important secondary metabolites in plants. However, their effects on microbial secondary metabolites were seldom reported. In this study, lanthanum (LaCl 3 ) was used as an elicitor in mycelium cultures of Shiraia bambusicola to stimulate the production of hypocrellin A (HA), a promising photosensitizer for anticancer photodynamic therapy. La 3+ at 1.0 g/L not only increases HA content by 2.50-fold in mycelia, but stimulates HA exudation to the medium with the highest production (225.05 mg/L) on day 6. Further analysis shows that La 3+ can induce the intracellular ROS (reactive oxygen species) accumulation with 2.33-fold higher contents of H 2 O 2 in mycelium. HA production induced by La 3+ treatment can be suppressed by ROS scavengers. Further analysis reveals that the elicitation of La 3+ on HA accumulation is mediated by ROS generation to enhance expression of HA biosynthetical genes. The expression of ATP-binding cassette transporter gene ( SbABC ) for HA exudation is also regulated partially via ROS generated by NADPH oxidase . These results indicate that the enhanced HA production by La 3+ might be mediated by ROS signaling pathway. Our results provide a basis for understanding REE elicitation on fungal metabolites and a practical biotechnological process for enhanced production of HA.