Jin-Soo Park

Autophagy inhibition enhances apoptosis induced by ginsenoside Rk1 in hepatocellular carcinoma cells.

Our previous study indicated that ginsenoside Rk1 has anti-tumor activity and that its mode of action in HepG2 cells treated for 48 h involves coordinated inhibition of telomerase and induction of apoptosis. In the present study, we found that Rk1 induces both G1 phase arrest and autophagy, but not apoptosis, at an earlier stage of treatment. A 24-h incubation of HepG2cells with Rk1 induced G1 phase arrest. Rk1-induced autophagy was documented by the conversion of microtubule associated protein light chain 3 (LC3)-I to LC3-II, an autophagosome marker, and monodansylcadaverine (MDC) incorporation into autolysosomes. Combination of Rk1 with an autophagy inhibitor, such as bafilomycin A1 or beclin 1 siRNA, enhanced the anti-tumor effect of Rk1. These results imply that autophagy functions as a survival mechanism in HepG2 cells against Rk1-induced apoptosis. Taken together, our results support the use of autophagy inhibitors in combination with Rk1 as an effective anti-cancer regimen in HepG2 cells.

Glionitrin B, a Cancer Invasion Inhibitory Diketopiperazine Produced by Microbial Coculture

A new diketopiperazine, glionitrin B (1), was produced using a microbial coculture of the fungus Aspergillus fumigatus KMC-901 and the bacterium Sphingomonas sp. KMK-001 that were isolated from acidic coal mine drainage. The structure of 1 was determined to be (3S,10aS)-dithiomethylglionitrin A. This structure was determined by the analyses of extensive NMR data and the circular dichroism spectra of the natural product and a semisynthetic compound derived from glionitrin A. In contrast to glionitrin A (2), glionitrin B (1) is not cytotoxic against the human prostate cancer cell line DU145. However, compound 1 caused suppression of DU145 cell invasion, producing 46% inhibition at 60 μM.

Aldgamycin I, an antibacterial 16-membered macrolide from the abandoned mine bacterium, Streptomyces sp. KMA-001.

Aldgamycin I, an antibacterial 16-membered macrolide from the abandoned mine bacterium, Streptomyces sp. KMA-001

Salinazinones A and B: Pyrrolidinyl-Oxazinones from Solar Saltern-Derived Streptomyces sp. KMF-004

Salinazinones A (1) and B (2), two unprecedented pyrrolidinyl-oxazinones, were isolated from the culture broth of Streptomyces sp. KMF-004 from a solar saltern at Aphae Island, Korea. The structures of these salinazinones, which are unusual and consist of 2-methylpropenyl-1,3-oxazin-6-one bearing 1-oxopyrrolidinyl substituents, were assigned by spectral and chemical analyses using Moshers method, circular dichroism (CD), and calculated ECD. Salinazinones are the first examples of a natural alkaloid class composed of an oxazinone-pyrrolidone conjugate.

Identification and Biosynthesis of New Acyloins from the Thermophilic Bacterium Thermosporothrix hazakensis SK20‐1T

Two new acyloin compounds were isolated from the thermophilic bacterium Thermosporothrix hazakensis SK20‐1T. Genome sequencing of the bacterium and biochemical studies identified the thiamine diphosphate (TPP)‐dependent enzyme Thzk0150, which is involved in the formation of acyloin. Through extensive analysis of the Thzk0150‐catalyzed reaction products, we propose a putative reaction mechanism involving two substrates: 4‐methyl‐2‐oxovalerate as an acyl donor and phenyl pyruvate as an acyl acceptor.

New 2-(1′ H -indole-3′-carbonyl)-thiazoles derived from the thermophilic bacterium Thermosporothrix hazakensis SK20-1 T

New 2-(1′ H -indole-3′-carbonyl)-thiazoles derived from the thermophilic bacterium Thermosporothrix hazakensis SK20-1 T

New Naphthoquinone Terpenoids from Marine Actinobacterium, Streptomyces sp. CNQ-509

A member of the marine streptomycete clade MAR4, Streptomyces sp. CNQ-509, has genetic potential for the biosynthesis of hybrid isoprenoids and produces several meroterpenoids such as naphterpin, nitropyrrolin and marinophenazine. Our research on the strain CNQ-509 led to the isolation of two new naphterpin derivatives (1 and 2) comprised of naphthoquinone and geranyl moieties along with the known terpenoid, debromomarinone. The two-dimensional structure of these compounds was determined through spectral data analysis using data from NMR, MS and UV spectroscopy. Furthermore, the full structures of 1 and 2 including absolute configurations were unequivocally established by a combination of NMR experiments and chemical modifications.

Pontemazines A and B, phenazine derivatives containing a methylamine linkage from Streptomyces sp. UT1123 and their protective effect to HT-22 neuronal cells.

New phenazine derivatives with a methylamine linker, Pontemazines A (1) and B (2), were isolated from the culture broth of Streptomyces sp. UT1123. The structures of compounds 1 and 2 were determined by NMR spectroscopy and high-resolution mass spectrometry. These compounds consist of a 9-mehoxyphenazine connected to a benzamide functional group by a unique methylamine linker instead of the more common methyl ether. Pontemazines A and B possess a neuronal cell protective effect on glutamate-induced mouse hippocampal HT-22 cell damage.

Production of chromopyrrolic acid by coexpression of inkOD in a heterologous host Streptomyces albus.

Two ink genes, inkO and inkD, responsible for the earliest steps of K252a biosynthetic pathway, from Nonomurea longicantena JCM 11136 were heterologously coexpressed in Streptomycesalbus J1074. The resultant strain accumulated compound that was purified by HPLC and studied by NMR. Coexpression of inkOD yielded chromopyrrolic acid, the key intermediate in an indolocarbazole biosynthesis.

Furanoaustinol and 7-acetoxydehydroaustinol: new meroterpenoids from a marine-derived fungal strain Penicillium sp. SF-5497.

Two new meroterpenoid-type fungal metabolites, furanoaustinol (1) and 7-acetoxydehydroaustinol (2), were isolated from the ethyl acetate extract of a marine-derived fungal strain Penicillium sp. SF-5497, along with eight (3–10) known meroterpenoids. Their structures were elucidated mainly based on the analysis of their NMR (1D and 2D) and MS data. Particularly, the novel meroterpenoid, furanoaustinol (1), belonging to the austin group, was identified to possess an unprecedented hexacyclic ring system. Biological evaluation of these compounds revealed that furanoaustinol (1) weakly inhibited the activity of protein tyrosine phosphatase 1B in a dose-dependent manner with an IC50 value of 77.2 μM. In addition, 7-acetoxydehydroaustinol (2) and four other known meroterpenoids (5, 7, 9, and 10) weakly suppressed the overproduction of nitric oxide in lipopolysaccharide-challenged BV2 microglial cells with IC50 values of 61.0, 30.1, 58.3, 37.6, and 40.2 μM, respectively.