Fungichromin production by Streptomyces sp. WP-1, an endophyte from Pinus dabeshanensis, and its antifungal activity against Fusarium oxysporum.

In this study, we isolated an endophytic Streptomyces sp. strain, WP-1, from surface-sterilized barks of Pinus dabeshanensis, an endangered Chinese plant. WP-1 showed strong antifungal activity against diverse pathogenic fungi, such as Fusarium oxysporum, Rhizoctonia solani, Phytophthora infestan, and Candida albicans. Based on phylogenetic analyses, preliminary identification suggested that the WP-1 strain belonged to the genus Streptomyces. Column chromatogram and HPLC were employed to isolate the primary antifungal component from the culture medium of WP-1, and it was identified as the methylpentaene macrolide antibiotic, fungichromin (FC). In this study, for the first time, using in vitro bioassay studies, we revealed that FC strongly inhibited mycelial growth and conidia germination in Fusarium oxysporum. The median inhibitory concentration of FC was found to be 3.80 mg/L. The fermentation conditions of the WP-1 strain were further investigated to improve FC production. We found that supplementation of the synthetic medium with oils (soybean oil, oleic acid, and so on), particularly during the initial stage of fermentation, significantly increased the FC yield. Ammonium-trapping agent (magnesium phosphate) was used as an additive to increase FC yield to 5741.7 mg/L. It was 2.9-fold more as compared to the highest FC yield reported so far where Streptomyces padanus PMS-702 was used for FC production. KEY POINTS: • Isolation and identification of a fungichromin-producing endophytic actinomycete WP-1 strain. • Fungichromin production was significantly improved via oils and ammonium-trapping agents addition. • Discovery of the antifungal activity of fungichromin against Fusarium oxysporum.

Chromenopyridin A, a new N-methoxy-1-pyridone alkaloid from the endophytic fungus Penicillium nothofagi P-6 isolated from the critically endangered conifer Abies beshanzuensis.

A new N-methoxy-1-pyridone alkaloid [chromenopyridin A (1)] and four known compounds (2-5) were isolated and identified from the endophytic fungus Penicillium nothofagi P-6, which was derived from the bark of the critically endangered conifer Abies beshanzuensis. Their structures were elucidated by extensive spectroscopic analyses and single-crystal X-ray diffraction. Among the isolates, compound 1 showed considerable cytotoxicities against the A549 and Hela human cancer cell lines, with IC50 values of 14.7 and 11.3 µM. In addition, compounds 1 and 4 exhibited potent antibacterial activity against Staphylococcus aureus with MIC values of 62.5 and 15.6 µg/mL, respectively.

Beshanzuamide A, an unprecedented prenylated indole alkaloid produced by Aspergillus sp. Y-2 from the critically endangered conifer Abies beshanzuensis.

A structurally unprecedented prenylated indole alkaloid, beshanzuamide A (1), together with five known analogues (2-6) were isolated and identified from the endophytic fungus derived from the needles of the critically endangered conifer Abies beshanzuensis. The new structure was determined by extensive spectroscopic methods and quantum chemical calculations of NMR and electronic circular dichroism (ECD) data. Compound 1 features a unique N,O-spiroketal/δ-lactone motif connected to a pyranoindole-derived bicyclo[2.2.2]diazaoctane ring. A plausible biogenetic pathway for the assembly of 1 was proposed.

Two new sterol derivatives isolated from the endophytic fungus Aspergillus tubingensis YP-2.

Two new sterol derivatives, namely ergosterimide B (1) and demethylincisterol A5 (2), along with eleven known metabolites (3-13), were isolated from the rice fermentation culture of Aspergillus tubingensis YP-2. The chemical structures were elucidated by detailed NMR and MS spectroscopic data and by comparison with reported data. Newly isolated compound 2 and known compound 3 were evaluated for their cytotoxicities against the A549 and HepG2 cell lines. Compound 2 showed weak activities with IC50 values of 11.05 and 19.15 µM, respectively, while 3 exhibited cytotoxicities with IC50 values of 5.34 and 12.03 µM, respectively, against the tested cell lines.

Aflatoxins from the endophytic fungus Aspergillus sp. Y-2 isolated from the critically endangered conifer Abies beshanzuensis.

Two new [asperxins A (1) and B (2)] and four known (3-6) aflatoxins were isolated and identified from the endophytic fungus Aspergillus sp. Y-2, which was derived from the needles of the critically endangered conifer Abies beshanzuensis. Their structures were elucidated by extensive spectroscopic methods. Among the isolates, compounds 1 and 5 showed considerable cytotoxicities against the A549 and Hela human cancer cell lines, with IC50 values in the range of 7.5-16.8 µM.

Discovery of Meso-(meta-Pyridinium) BODIPY Photosensitizers: In Vitro and In Vivo Evaluations for Antimicrobial Photodynamic Therapy.

Antimicrobial photodynamic therapy (aPDT) has emerged as a novel and promising approach for the treatment of pathogenic microorganism infections. The efficacy of aPDT depends greatly on the behavior of the photosensitizer. Herein, we report the design, preparation, antimicrobial photodynamic activities, as well as structure-activity relationships of a series of photosensitizers modified at the meso position of a 1,3,5,7-tetramethyl BODIPY scaffold with various pyridinyl and pyridinium moieties. The photodynamic antimicrobial activities of all photosensitizers have been tested against Staphylococcus aureus, Escherichia coli, Candida albicans, and Methicillin-resistant S. aureus (MRSA). The methyl meso-(meta-pyridinium) BODIPY photosensitizer (3c) possessed the highest phototoxicity against these pathogens at minimal inhibitory concentrations (MIC) ranging from 0.63 to 1.25 µM with a light dose of 81 J/cm2. Furthermore, 3c exhibited an impressive antimicrobial efficacy in S. aureus-infected mice wounds. Taken together, these findings suggest that 3c is a promising candidate as the antimicrobial photosensitizer for combating pathogenic microorganism infections.

Anchoring BODIPY photosensitizers enable pan-microbial photoinactivation.

Photodynamic antimicrobial chemotherapy (PACT) is an effective strategy to inactivate pathogenic and resistant microbes. However, pan-microbial photoinactivation has hardly achieved. In this manuscript, we built anti-microbial PSs based on 2,6-diiodo-1,3,5,7-tetramethyl BODIPY (2I-BDP) using anchoring strategy through modifications on boron atom with bis-cationic moieties. With appropriate bis-cationic anchoring, we could achieve effective PACT for pan-microbial photoinactivation via straight forward modifications. Our studies suggested that integration of an efficient photosensitizer, good amphiphilicity, as well as tight interaction with microbial membrane could be essential for effective PACT.