Enhanced production of hypocrellin A by ultrasound stimulation in submerged cultures of Shiraia bambusicola

Abstract Hypocrellin A (HA), a naturally occurring fungal perylenequinone, is widely used in clinic to treat skin diseases and developed as a photodynamic therapy (PDT) agent against cancers. In this study, a low intensity ultrasound (US, 0.28 W/cm 2 at 40 kHz) was conducted thrice of repeated US exposure (5-min) with an interval of 12 h to stimulate HA production of Shiraia bambusicola after 72 h of the initial submerged cultures. US not only increased the content of HA by 177.2% in mycelia, but stimulated the release of HA into the medium with the highest total production of HA (247.67 mg/L) on day 8. US could result in the decreased pellet diameter, the enhanced membrane permeability, the alternation of membrane compounds and reactive oxygen species (ROS) generation. Furthermore, the ultrasonic treatment up-regulated the expression of some HA biosynthetic genes including polyketide synthase gene ( PKS) , O -methyltransferase gene ( Omef ), O -methyltransferase/FAD-dependent monooxygenase ( Mono ) and FAD/FMN-dependent oxidoreductase gene ( FAD ), and activated major facilitator superfamily transporter gene ( MFS ) for HA exudation. The enhancement of HA production was mainly due to both the stimulated cellular biosynthesis and the enhanced fungal exudation of HA. These results provide a basis for understanding the US elicitation and a valuable strategy for enhancing HA production in submerged Shiraia cultures.