Enhanced Production of Hypocrellin A in Submerged Cultures of Shiraia bambusicola by Red Light

Abstract

Hypocrellin A (HA), a promising photosensitizer for anticancer photodynamic therapy (PDT), is a fungal perylenequinone pigment from the fruiting body of Shiraia bambusicola, a traditional Chinese medicine for treating skin diseases. The mycelial cultures are becoming a biotechnological alternative for HA production. In this study, light of different wavelengths was investigated to develop an effective eliciting strategy for HA production in the cultures. Under red LED light (627 nm) at 200 lux, the maximum HA production (175.53 mg L−1) in mycelium cultures was reached after 8 days, about 3.82‐fold of the dark control. Red light not only promoted HA biosynthesis in mycelia (intracellular HA), but also stimulated HA secretion into the medium (extracellular HA). We found 14 of 310 transcripts differentially expressed under red light treatment were possible candidate genes for HA biosynthetic pathway. Gene ontology (GO) analysis revealed that red light treatment could change the gene expressions responsible for HA biosynthesis and the transmembrane activity, suggesting both intracellular HA and its secretion could contribute to the enhancement of total HA production in the cultures. The results provided new insights of red light elicitation and effective strategy for HA production in mycelium cultures.

Nitric Oxide and Hydrogen Peroxide Signaling in Extractive Shiraia Fermentation by Triton X-100 for Hypocrellin A Production

“…Due to the limitations of the wild fungal fruiting bodies and complexity of total chemical synthesis of HA [3], Shiraia mycelium culture has become a biotechnological alternative for HA production [4]. Since lower HA yield is the bottleneck of biotechnological production of HA in Shiraia fermentation, many process strategies have been applied to Shiraia cultures, including medium optimization, treatment of fungal elicitor [5,6], ultrasound stimulation [7] and light radiation [8,9]. Liu et al (2016) managed to mutagenize Shiraia spores using cobalt-60 gamma irradiation to obtain mutated strains for higher HA production [10].…”

“…However, there has been, so far, few reports regarding the regulation of NO on fungal metabolism, and no reports regarding physiological responses, especially on NO and ROS signaling during surfactant exposure in mycelium cultures. Therefore, as a follow-up exploration on stimulating HA production in the fermentation under elicited conditions including the treatments of fungal elicitor [24], the sonication of low-energy ultrasound [7,25], and the radiation of ultraviolet-B [26] or red light [9], we wish to explore the physiological role of NO and ROS in mycelium cultures of S. bambusicola in nonionic surfactant micelle aqueous solution. This study may help us understand the mechanism or the signaling regulation in fungal extractive fermentation and provide a novel process strategy for HA production in Shiraia fermentation.…”

Inducing perylenequinone production from a bambusicolous fungus Shiraia sp. S9 through co-culture with a fruiting body-associated bacterium Pseudomonas fulva SB1

“…10). It has been reported previously that higher HA yield under the elicitation of a repeated ultrasound [27], light–dark shift [28] and red light [29] was from 175.53 to 247.67 mg/L. Compared with these elicitation techniques, the established co-culture is of great potential to be a novel strategy for the biotechnological production for HA production.…”

Bacteria Associated With Shiraia Fruiting Bodies Influence Fungal Production of Hypocrellin A

“…HA yield was achieved as 2.02 mg/g (dry solid substrate) in the solid cultures (Liang et al, 2009) and about 10–40 mg/L in liquid mycelium cultures (Liu et al, 2009). Thus, many strategies have been applied to enhance HA production in the mycelium cultures, including optimizing the cultural medium (Yang et al, 2013), elicitation (Cai et al, 2011; Du et al, 2013; Ma et al, 2019), and molecular engineering (Gao et al, 2018). In our previous study (Sun et al, 2017), the highest HA production (247.67 mg/L) was obtained under the elicitation of a repeated ultrasound.…”

“…An enhanced production (up to 78-fold) of known metabolites and three new natural products were identified only in co-cultures of the endophytic Fusarium tricinctum with the bacterium B. subtilis 168 trpC2 (Ola et al, 2013). Compared to other abiotic elicitors such as ultrasound, light–dark shift, Triton X-100, and red light (Lei et al, 2017; Sun et al, 2017, 2018; Ma et al, 2019), bacterial treatment is simple and easily prepared without the need for complex equipment. It is worth mentioning that bacterial co-culture at the desired condition exhibited no suppression of fungal biomass (Figure 10A), suggesting an effective strategy for improving HA production in mycelium cultures.…”