Nitric oxide donor sodium nitroprusside-induced transcriptional changes and hypocrellin biosynthesis of Shiraia sp. S9

Abstract

Background Nitric oxide (NO) is a ubiquitous signaling mediator in various physiological processes. However, there are less reports concerning the effects of NO on fungal secondary metabolites. Hypocrellins are effective anticancer photodynamic therapy (PDT) agents from fungal perylenequinone pigments of Shiraia. NO donor sodium nitroprusside (SNP) was used as a chemical elicitor to promote hypocrellin biosynthesis in Shiraia mycelium cultures. Results SNP application at 0.01–0.20 mM was found to stimulate significantly fungal production of perylenequinones including hypocrellin A (HA) and elsinochrome A (EA). SNP application could not only enhance HA content by 178.96% in mycelia, but also stimulate its efflux to the medium. After 4 days of SNP application at 0.02 mM, the highest total production (110.34 mg/L) of HA was achieved without any growth suppression. SNP released NO in mycelia and acted as a pro-oxidant, thereby up-regulating the gene expression and activity of reactive oxygen species (ROS) generating NADPH oxidase (NOX) and antioxidant enzymes, leading to the increased levels of superoxide anion (O2−) and hydrogen peroxide (H2O2). Gene ontology (GO) analysis revealed that SNP treatment could up-regulate biosynthetic genes for hypocrellins and activate the transporter protein major facilitator superfamily (MFS) for the exudation. Moreover, SNP treatment increased the proportion of total unsaturated fatty acids in the hypha membranes and enhanced membrane permeability. Our results indicated both cellular biosynthesis of HA and its secretion could contribute to HA production induced by SNP. Conclusions The results of this study provide a valuable strategy for large-scale hypocrellin production and can facilitate further understanding and exploration of NO signaling in the biosynthesis of the important fungal metabolites.

Nitric oxide mediates red light-induced perylenequinone production in Shiraia mycelium culture

“…In our previous work, we observed that the intracellular HA content of Shiraia sp. S9 increased by 73.31–178.96% when treated with 0.02 mM SNP on day 3 of a 9-day-culture (Ma et al 2021 ). Additionally, Zhao et al ( 2021a ) reported that exogenous addition of 0.01 mM SNP promoted PQ production (HA and elsinochrome A) in S. bambusicola S4201 by 156% compared to the control.…”

“…However, there have been no reports regarding NO generation in fungi induced by red light or its signaling roles in fungal secondary metabolite biosynthesis. Therefore, as a follow-up to our efforts to promote Shiraia HA production by light (Ma et al 2019a ) and understand the physiological roles of NO during the abiotic elicitation on Shiraia fungi (Li et al 2020 ; Ma et al 2021 ), we therefore wish to investigate red light-induced NO generation and its relationship with other eliciting responses, including ROS production, Ca 2+ fluxes, extracellular ATP (eATP) levels, and Shiraia PQ biosynthesis. Additionally, a novel strategy involving combined elicitation with SNP (a NO donor) and red light is established for biotechnological production of hypocrellins in mycelium cultures.…”

2-Methoxy-1,4-naphthoquinone regulated molecular alternation of Fusarium proliferatum revealed by high-dimensional biological data

“…Unsaturated fatty acids such as linolenic acid and linoleic acid will produce H 2 O 2 and free radicals, damaging the structure of the cell membrane. 52 The permeability of the cell membrane will be changed and the permeability of the cell contents will increase when the membrane structure was destroyed, which will lead to an increase in the relative electrical conductivity. 27 However, metabolites such as betaine, l -proline, succinate, and 2-isopropylmalic acid increased, altering the membrane lipid peroxidation and osmotic pressure, resulting in reduced MDA concentration and relative electrical conductivity in the treatment group compared to the control group.…”

Industrial Production of Antibiotics in Fungi: Current State, Deciphering the Molecular Basis of Classical Strain Improvement and Increasing the Production of High-Yielding Strains by the Addition of Low-Molecular Weight Inducers

“…also leads to an increase in NO production, which is accompanied by an increase in the production of a number of SMs [308]. The addition of an NO donor (sodium nitroprusside) to the mold Shiraia sp., which is used in traditional Chinese medicine, led to an increase in the production of perylenequinone pigments, in particular hypocrellin A [309][310][311], a promising photosensitizer for anticancer photodynamic therapy [312]. In addition, enzymes that control cellular NO content, such as P450nor (cytochrome P450 nitric oxide reductase), may also affect the biosynthesis of SMs in fungi [313].…”