Optimal fermentation time for Nigrospora-fermented tea rich in bostrycin.

BACKGROUND: Bostrycin has many biological functions, such as anticancer activity, and is becoming increasingly popular. Nigrospora sphaerica HCH285, which has the ability to produce high levels of bostrycin, can be used to ferment sun-dried green tea of Camellia sinensis through acclimation, resulting in the development of a Nigrospora-fermented tea. The effects of fermentation time on the production of bostrycin by the HCH285 strain were investigated. RESULTS: After 45 days of fermentation, the bostrycin content reached 3.18 g kg-1 , which is the highest level during the whole fermentation. At 50 days, the tea liquor was red, had a strong mushroom odour and a sweet taste, and presented optimal quality. The contents of free amino acids, tea polyphenols and soluble sugars in the fermented tea decreased generally during the fermentation, although the content of water-soluble substances increased. Additionally, the results of a 14-day acute oral toxicity test showed that Nigrospora-fermented tea was nontoxic. CONCLUSION: The optimum fermentation time of Nigrospora-fermented tea was concluded to be 45-50 days. These results provide insights with respect to the development of tea biotechnology and new tea products with active ingredients. © 2020 Society of Chemical Industry.

Optimization and characterization of red pigment production from an endophytic fungus, Nigrospora aurantiaca CMU-ZY2045, and its potential source of natural dye for use in textile dyeing.

Some of the most important natural pigments have been produced from fungi and used for coloring in food, cosmetics, textiles, and pharmaceutical products. Forty-seven isolates of endophytic fungi were isolated from Cinnamomum zeylanicum in northern Thailand. Only one isolate, CMU-ZY2045, produced an extracellularly red pigment. This isolate was identified as Nigrospora aurantiaca based on morphological characteristics and the molecular phylogenetic analysis of a combined four loci (large subunit and internal transcribed spacer of ribosomal DNA, ß-tubulin, and translation elongation factor 1-alpha genes). The optimum conditions for red pigment production from this fungus were investigated. The results indicated that the highest red pigment yield was observed in the liquid medium containing glucose as a carbon source and yeast extract as a nitrogen source, at a pH value of 5.0 and at 27 °C with shaking for 5 days. The crude red pigment revealed the highest level of solubility in methanol. A fungal red pigment was found to have high stability at temperatures ranging from 20 to 50 °C and pH values at a range of 5.0-6.0. Based on liquid chromatography-mass spectrometry analyses, the red pigment was characterized as bostrycin. The extracted pigment was used for the textile dyeing process. Crude fungal red pigment revealed the highest staining ability in cotton fabrics and displayed excellent fastness to washing, which showing negative cytotoxicity at the concentrations used to cell culture. This is the first report on bostrycin production from N. aurantiaca.

Studies on the synthesis of derivatives of marine-derived bostrycin and their structure-activity relationship against tumor cells.

A series of new derivatives (5-29) of marine-derived bostrycin (1) were synthesized. The in vitro cytotoxic activities of all compounds were evaluated against MCF-7, MDA-MB-435, A549, HepG2, HCT-116 and MCF-10A cells using the MTT method. The compounds 7, 8, 22, 23, 25, 28 and 29 of the total showed comparable activity to epirubicin, the positive control, against the tested cancer cell lines. However, these compounds also exhibited cytotoxicity towards MCF-10A cells. The structure-activity relationship (SAR) of bostrycin derivatives was also discussed based on the obtained experimental data.

Proteomic characterization of Mycobacterium tuberculosis reveals potential targets of bostrycin.

Tuberculosis (TB) is caused by bacterial pathogen Mycobacterium tuberculosis (Mtb) and remains a major health problem worldwide. The increasing prevalence of drug-resistant Mtb strains and the extended duration of anti-TB regimens have created an urgent need for new anti-tuberculosis antibiotics with novel targets or inhibitory strategies. Anthracenedione compound bostrycin has been shown to inhibit the growth of Mtb in vitro and inhibit the activity of the effector protein tyrosine phosphatase (MptpB) secreted by Mtb. In this study, we characterized the proteomic profile of the Mtb strain H37Ra exposed to 1 mg/L and 25 mg/L of bostrycin for 24 h. Bioinformatic analysis of the differential abundant proteins indicated that bostrycin treatment may induce oxidative stress and interfere with essential processes such as synthesis of NAD(+) and the tricarboxylic acid cycle in mycobacteria. Then, the molecular docking of bostrycin and 15 candidates of targeted proteins showed that Rv3684 and Rv1908c got higher scores compared to MptpB, suggesting the direct interaction of bostrycin and these two proteins. Further docking of potential targeted proteins with the functional group-removal derivatives of bostrycin revealed possible key functional groups of bostrycin and provides direction for the modification of bostrycin in future. BIOLOGICAL SIGNIFICANCE: It is a challenging work to determine the potential target(s) of an antibiotic accurately and quickly. In this study, we conducted a proteomic analysis of Mtb responding to the treatment of bostrycin, and provided insight into the inhibiting mechanism of this anti-Mtb compound. The proper interaction of bostrycin and targeted proteins, as well as the interacting residues of targets, and functional groups of bostrycin were also identified within the docking surface, providing a direction for further modification of bostrycin. Our study also suggests a reference for the interaction analysis between mycobacteria and antibiotics, and provides potential targets information for other active anthraquinones.

Bostrycin inhibits growth of tongue squamous cell carcinoma cells by inducing mitochondrial apoptosis.

BACKGROUND: Bostrycin is a natural pigment product with anthraquinone skeleton, which has excellent inhibitory effect on a variety cancer cells. However, its suppression on tongue squamous cell carcinoma has not been reported. METHODS: We studied the effects of bostrycin on the cell growth and apoptosis of tongue squamous cell carcinoma in vitro, and explored its mechanism. RESULTS: Bostrycin could inhibit the proliferation and migration of tongue squamous cell carcinoma by arresting cell cycle at G2/M phase, and inducing cell apoptosis with mitochondrial membrane potential changes. West-blotting analysis also showed that bostrycin could inhibit the growth of tongue squamous cell carcinoma cells by activating the apoptosis-related signal proteins especially in mitochondrial apoptotic pathway. CONCLUSIONS: Bostrycin can be used as a new anti-tumor candidate drug for further research. Our study provides reference for the potential application of bostrycin in the treatment of the tongue squamous cell carcinoma.

Bioactivities and Structure-Activity Relationships of Natural Tetrahydroanthraquinone Compounds: A Review.

Tetrahydroanthraquinones are a kind of important microbial secondary metabolites with promising biological activities. Most of them were found in microorganisms, a few were derived from Chinese herbal medicine. In this review, aiming to provide basis for the further research and development of tetrahydroanthraquinone compounds, we summarized the physiological activities of natural tetrahydroanthraquinone compounds, including anti-cancer, anti-microbial, and antidiabetic activities. The source, structure, and action mechanisms of active tetrahydroanthraquinones are described in detail. Furthermore, this review firstly analyzed the structure-activity relationship of tetrahydroanthraquinones. Our study will serve as a valuable guideline for further research on the structural optimization, mechanism study, and development of tetrahydroanthraquinone as novel drugs. Aiming to provide references for further studies and development of tetrahydroanthraquinone compounds.

Bostrycin production by agro-industrial residues and its potential for food processing.

Bostrycin, a red antibacterial agent produced by Nigrospora sp. no. 407, is considered for meat processing. To optimize production, the culture conditions of submerged fermentation (SmF) and solid-state fermentation (SSF) were investigated. The optimal SmF conditions were a medium containing 1.0% cane molasses and incubation at 30 °C and 150 rpm for 6 days. In SSF, other than bostrycin, less pigment was produced and the optimal ratio of bagasse to water was 1:2 for 10 days. The production and recovery rate of bostrycin by SmF were 120 mg/L and 40%, respectively. Bostrycin exhibited thermostable, pH-dependent color change and dose-dependent antibacterial activity against Clostridium botulinum. Bostrycin-modified meat turned strong red for at least 24 h and could not be removed by washing; bostrycin maintained its antibacterial activity with a bacteriostasis rate of 91% on Staphylcoccus aureus. This is an easy and inexpensive means of acquiring bostrycin from molasses and sugarcane.