Induction of Fungal Secondary Metabolites by Co-Culture with Actinomycete Producing HDAC Inhibitor Trichostatins.

A recently bioinformatic analysis of genomic sequences of fungi indicated that fungi are able to produce more secondary metabolites than expected. Despite their potency, many biosynthetic pathways are silent in the absence of specific culture conditions or chemical cues. To access cryptic metabolism, 108 fungal strains isolated from various sites were cultured with or without sp.

Ulleungdolin, a Polyketide-Peptide Hybrid Bearing a 2,4-Di--methyl-β-d-antiarose from sp. 13F051 Co-cultured with 15S071.

A new secondary metabolite, ulleungdolin (), was isolated from the co-culture of an actinomycete, sp. 13F051, and a fungus, 15S071. Based on the NMR, UV, and MS data, it was deduced that the planar structure of comprised an isoindolinone (IsoID) with an octanoic acid, a tripeptide, and a sugar.

Jejuketomycins A and B, polyketide glycosides with cancer cell migration inhibitory activity from sp. KCB15JA151.

Two new polyketide glycosides jejuketomycins A (1) and B (2), were isolated from a culture of sp. KCB15JA151. Their chemical structures including the absolute configurations were determined by detailed analyses of the NMR and HRMS data and ECD calculations and spectral data.

Jejucarbazoles A-C, carbazole glycosides with indoleamine 2,3-dioxygenase 1 inhibitory activity from sp. KCB15JA151.

A bioassay-guided investigation led to the isolation of three new carbazole glycosides, jejucarbazoles A-C (1-3), from sp. KCB15JA151. Their planar structures were elucidated by detailed NMR and MS spectroscopic analysis with a literature study.

Near-Infrared Fluorescence Probe for Specific Detection of Acetylcholinesterase and Imaging in Live Cells and Zebrafish.

Acetylcholinesterase (AChE) is a pivotal enzyme that is closely related with multiple neurological diseases, such as brain disorders or alterations in the neurotransmission and cancer. The development of convenient methods for imaging AChE activity in biological samples is very important to understand its mechanisms and functions in a living system. Herein, a fluorescent probe exhibiting emission in the near-infrared (NIR) region is developed to detect AChE and visualize biological AChE activities.

Kurarinone induced p53-independent G0/G1 cell cycle arrest by degradation of K-RAS via WDR76 in human colorectal cancer cells.

Kurarinone (KR), a naturally occurring flavonoid in Sophora flavescens Aiton and a traditional herbal medicine, reportedly has anti-cancer activity against various cancer types both in vitro and in vivo. However, the cellular mechanism of KR remains unknown. Therefore, we aimed to elucidate the mechanism of cell cycle arrest induced by KR in human colorectal cancer cells.

New phenalenone derivatives from the Hawaiian volcanic soil-associated fungus Penicillium herquei FT729 and their inhibitory effects on indoleamine 2,3-dioxygenase 1 (IDO1).

Phenalenone derivatives sourced from fungi are polyketides that have attracted significant interest because of their diverse chemical structures and potential bioactivities. As part of our ongoing quest to discover novel natural products with biological properties from diverse natural resources, three unreported phenalenone derivatives (1-3), named ent-12-methoxyisoherqueinone (1), (-)-scleroamide (2), and (+)-scleroamide (3), together with four known phenalenone derivatives, ent-atrovenetinone (4), isoherqueinone (5), herqueinone (6), and ent-peniciherquinone (7) were isolated from the Hawaiian soil fungus Penicillium herquei FT729, collected on the Big Island, Hawaii. Compounds 2 and 3 were enantiomers, which were separated using a chiral-phase HPLC column, which provided optically pure compounds 2 and 3.

RK-270D and E, Oxindole Derivatives from sp. with Anti-Angiogenic Activity.

A chemical investigation of a culture extract from sp. RK85-270 led to the isolation and characterization of two new oxindoles, RK-270D (1) and E (2). The structures of 1 and 2 were determined by analyzing spectroscopic and spectrometric data from 1D and 2D NMR and High-resolution electrospray ionization mass spectrometry (HRESIMS) experiments.

Streptooctatins A and B, fusicoccane-type diterpenoids with autophagic activity from Streptomyces sp. KCB17JA11.

Two new fusicoccane-type diterpenoids, streptooctatins A (1) and B (2), together with a known compound cyclooctatin (3) were isolated from Streptomyces sp. KCB17JA11. The structures of 1 and 2 were determined by analyzing spectroscopic and spectrometric data from 1D and 2D NMR and HRESIMS experiments.

Regulation of Survival Motor Neuron Gene Expression by Calcium Signaling.

Spinal muscular atrophy (SMA) is caused by homozygous () gene deletion, leaving a duplicate gene, , as the sole source of SMN protein. However, a defect in SMN2 splicing, involving exon 7 skipping, results in a low level of functional SMN protein. Therefore, the upregulation of SMN protein expression from the gene is generally considered to be one of the best therapeutic strategies to treat SMA.

Thiolactomide: A New Homocysteine Thiolactone Derivative from sp. with Neuroprotective Activity.

A new homocysteine thiolactone derivative, thiolactomide (1), was isolated along with a known compound, -acetyl homocysteine thiolactone (2), from a culture extract of soil-derived sp. RK88-1441. The structures of these compounds were elucidated by detailed NMR and MS spectroscopic analyses with literature study.

Ulleunganilines A-C, Trichostatin Analogues Bearing a Modified Side Chain from sp. 13F051.

Three new trichostatin analogues, ulleunganilines A-C (-), and seven known trichostatins (-) were isolated from cultures of sp. 13F051. NMR, UV, and MS data indicated that the planar structures of - consisted of modified side chains in the trichostatic acid moiety.

Angucyclines containing β-ᴅ-glucuronic acid from Streptomyces sp. KCB15JA151.

Two angucyclines, pseudonocardones D (1) and E (2), were isolated from Streptomyces sp. KCB15JA151. The planar structure was elucidated by comprehensive spectroscopic analysis.

Dutomycin Induces Autophagy and Apoptosis by Targeting the Serine Protease Inhibitor SERPINB6.

Autophagy plays an important role in maintaining tumor cell progression and survival in response to metabolic stress. Thus, the regulation of autophagy can be used as a strategy for anticancer therapy. Here, we report dutomycin (DTM) as a novel autophagy enhancer that eventually induces apoptosis due to excessive autophagy.

-Peniciherqueinone Suppresses Acetaldehyde-Induced Cytotoxicity and Oxidative Stress by Inducing ALDH and Suppressing MAPK Signaling.

Studies on ethanol-induced stress and acetaldehyde toxicity are actively being conducted, owing to an increase in alcohol consumption in modern society. In this study, -peniciherqueinone (EPQ) isolated from a Hawaiian volcanic soil-associated fungus FT729 was found to reduce the acetaldehyde-induced cytotoxicity and oxidative stress in PC12 cells. EPQ increased cell viability in the presence of acetaldehyde-induced cytotoxicity in PC12 cells.

A pipecolic acid-rich branched cyclic depsipeptide ulleungamide C from a Streptomyces species induces G0/G1 cell cycle arrest in promyelocytic leukemia cells.

In this study, screening by LC-MS and cytotoxicity-guided isolation led to the identification of ulleungamide C (1), a previously unknown pipecolic acid-rich branched cyclic depsipeptide, from a soil actinobacterium Streptomyces sp. KCB13F003. The structure of 1 was determined by interpretation of spectroscopic and spectrometric data from 1D and 2D NMR and HRESIMS experiments.

Herqueilenone A, a unique rearranged benzoquinone-chromanone from the Hawaiian volcanic soil-associated fungal strain Penicillium herquei FT729.

The study of a Hawaiian volcanic soil-associated fungal strain Penicillium herquei FT729 led to the isolation of one unprecedented benzoquinone-chromanone, herqueilenone A (1) and two phenalenone derivatives (2 and 3). Their structures were determined through extensive analysis of NMR spectroscopic data and gauge-including atomic orbital (GIAO) NMR chemical shifts and ECD calculations. Herqueilenone A (1) contains a chroman-4-one core flanked by a tetrahydrofuran and a benzoquinone with an acetophenone moiety.

Highly oxygenated angucycline from Streptomyces sp. KCB15JA014.

LC/MS-based chemical screening of culture extract led to a new highly oxygenated angucycline derivative, grecocycline D (1), from Streptomyces sp. KCB15JA014, isolated from a soil sample of Oedolgae in Jeju Island, Korea. The planar structure was determined on the basis of spectroscopic analysis, including 1D and 2D NMR techniques as well as HRESIMS and comparison with data from the literature.

Cytotoxic Activities and Molecular Mechanisms of the Beauvericin and Beauvericin G Microbial Products against Melanoma Cells.

Melanoma is the most serious type of skin cancer and remains highly drug-resistant. Therefore, the discovery of novel effective agents against melanoma is in high demand. Herein, we investigated the cytotoxic activities in melanoma cells and underlying molecular mechanisms of beauvericin (BEA) and its analogue beauvericin G (BEA G), which are cyclohexadepsipeptides isolated from fungi.

Xyloneside A: A New Glycosylated Incisterol Derivative from Xylaria sp. FB.

Xylaria species are prolific natural product producers. Here, we report the characterization of a new glycosylated incisterol derivative, called xyloneside A (1) and two known lignans (2 and 3) from the ascomycetous Xylaria sp. FB.

Kushenol E inhibits autophagy and impairs lysosomal positioning via VCP/p97 inhibition.

Autophagy plays a major role in cell survival and has therefore been exploited as an important strategy in cancer therapy. In this study, we evaluated the autophagy-regulatory effects of kushenol E (KE), a bi-prenylated flavonoid isolated from Sophora flavescens and found that KE increased LC3B-II levels while inducing the formation of autophagic vacuoles and immature autophagosomes in HeLa and HCT116 cells. Transmission electron microscopy images revealed that KE treatment generates immature autophagosomes.

Catenulisporidins A and B, 16-membered macrolides of the hygrolidin family produced by the chemically underexplored actinobacterium Catenulispora species.

Two new macrolide metabolites of the hygrolidin family, catenulisporidins A and B (1 and 2), together with a known compound hygrolidin (3), were isolated from the culture broth of the rare actinobacterium Catenulispora sp. KCB13F192. Their structures were elucidated on the basis of HRESIMS spectrometric and NMR spectroscopic analyses.

Antiangiogenic potentials of ahpatinins obtained from a Streptomyces species.

While exploring new angiogenesis inhibitors from microbial metabolites, we recently isolated ahpatinins C, E, and G from a soil‑derived Streptomyces sp. 15JA150. Ahpatinins C, E and G are known to have pepsin and renin inhibitory activities; however, their antiangiogenic activities and underlying molecular mechanisms have not been fully elucidated.

Isolation of new streptimidone derivatives, glutarimide antibiotics from Streptomyces sp. W3002 using LC-MS-guided screening.

A LC-MS-guided screening led to the isolation of two new streptimidone derivatives (2 and 3) containing a glutarimide ring and two glutarimide ring-opened compounds (4 and 5) along with a known glutarimide-containing polyketide, streptimidone (1) from Streptomyces sp. W3002 strain. Their structures were elucidated by MS and NMR spectroscopic analyses and by comparison with data from the literature.

CRM646-A, a Fungal Metabolite, Induces Nucleus Condensation by Increasing Ca Levels in Rat 3Y1 Fibroblast Cells.

We previously identified a new heparinase inhibitor fungal metabolite, named CRM646-A, which showed inhibition of heparinase and telomerase activities in an in vitro enzyme assay and antimetastatic activity in a cell-based assay. In this study, we elucidated the mechanism by which CRM646-A rapidly induced nucleus condensation, plasma membrane disruption and morphological changes by increasing intracellular Ca levels. Furthermore, PD98059, a mitogen-activated protein kinase (MEK) inhibitor, inhibited CRM646-A-induced nucleus condensation through ERK1/2 activation in rat 3Y1 fibroblast cells.