Inho Yang

Phosphoiodyns A and B, Unique Phosphorus-Containing Iodinated Polyacetylenes from a Korean Sponge Placospongia sp.

Two unprecedented phosphorus-containing iodinated polyacetylenes, phosphoiodyns A and B (1-2), were isolated from a Korean marine sponge Placospongia sp. Their structures were elucidated by spectroscopic data analysis. Phosphoiodyn A exhibited potent agonistic activity on human peroxisome proliferator-activated receptor delta (hPPARδ) with an EC(50) of 23.7 nM.

Anmindenols A and B, Inducible Nitric Oxide Synthase Inhibitors from a Marine-Derived Streptomyces sp.

Anmindenols A (1) and B (2), inhibitors of inducible nitric oxide synthase (iNOS), were isolated from a marine-derived bacterium Streptomyces sp. Their chemical structures were elucidated by interpreting various spectroscopic data, including IR, MS, and NMR. Anmindenols A and B are sesquiterpenoids possessing an indene moiety with five- and six-membered rings derived from isoprenyl units. The absolute configuration of C-4 in anmindenol B was determined by electronic circular dichroism (ECD) of a dimolybdenum complex. Anmindenols A (1) and B (2) inhibited nitric oxide production in stimulated RAW 264.7 macrophage cells with IC50 values of 23 and 19 μM, respectively.

Acredinones A and B, Voltage-Dependent Potassium Channel Inhibitors from the Sponge-Derived Fungus Acremonium sp. F9A015

Two new benzophenones, acredinones A (1) and B (2), were isolated from a marine-sponge-associated Acremonium sp. fungus. Their chemical structures were elucidated on the interpretation of spectroscopic data. The structure of 1 was confirmed by palladium-catalyzed hydrogenation, followed by spectroscopic data analysis. Acredinones A (1) and B (2) inhibited the outward K(+) currents of the insulin secreting cell line INS-1 with IC50 values of 0.59 and 1.0 μM, respectively.

Developing Streptomyces venezuelae as a cell factory for the production of small molecules used in drug discovery

The heterologous expression of biosynthetic pathways is an indispensable tool for drug discovery and development from natural products. Streptomyces venezuelae is a promising heterologous host as it offers several attractive advantages, such as rapid growth rate, convenient genetic manipulation, and an abundant supply of common biosynthetic building blocks. In recent decades, several S. venezuelae mutant strains have been constructed and used to facilitate the synthesis and derivatization of diverse natural products. In this review article, we have provided a schematic look at these host strains, which were used to synthesize natural products from genetically engineered biosynthetic gene clusters.

Anithiactins A-C, modified 2-phenylthiazoles from a mudflat-derived Streptomyces sp.

Intensive investigation of the chemical components of a Streptomyces sp. isolated from mudflat sediments collected on the southern coast of the Korean peninsula led to the isolation of three new compounds, anithiactins A-C (1-3). The chemical structures of anithiactins A and C were determined by interpretation of NMR data analyses, while the chemical structure of anithiactin B was established from a combination of NMR spectroscopic and crystallographic data analyses. The structure of anithiactin A was also confirmed by total synthesis. These three anithiactins displayed moderate acetylcholinesterase inhibitory activity with no significant cytotoxicity.

Nocarimidazoles A and B from a Marine-Derived Actinomycete of the Genus Nocardiopsis

Chemical investigation of a marine-derived actinomycete isolated from marine sediments collected off the coast of southern California and identified as a Nocardiopsis sp. (strain CNQ115) led to the isolation of two new 4-aminoimidazole alkaloids, nocarimidazoles A (1) and B (2). The chemical structures of nocarimidazoles A and B were assigned by interpretation of NMR spectroscopic data and through methylation to yield monomethyl and dimethyl derivatives. Nocarimidazoles A and B possess a 4-aminoimidazole ring combined with a conjugated carbonyl side chain, which is rarely found in microbial secondary metabolites.

Monanchosterols A and B, Bioactive Bicyclo[4.3.1]steroids from a Korean Sponge Monanchora sp.

Chemical investigation of a Korean marine sponge, Monanchora sp., led to the isolation of three new steroids (1-3). Compounds 1 and 2, designated as monanchosterols A and B, respectively, represent the first examples of steroids possessing the bicyclo[4.3.1] A/B ring system from a natural source. Compounds 1-3 were investigated for their anti-inflammatory activity by evaluating their inhibitory effects on the mRNA expression of IL-6, TNF-α, and COX-2 in the LPS-stimulated murine RAW264.7 macrophage cells. Compounds 2 and 3 exhibited significant inhibitory effects on the mRNA expression of IL-6 without notable cytotoxicity to the cells in a dose-dependent manner.

Ansalactams B–D Illustrate Further Biosynthetic Plasticity within the Ansamycin Pathway

Further chemical investigation of a marine-derived bacterium of the genus Streptomyces has led to the isolation of ansalactams B-D (1-3) along with the previously reported metabolite ansalactam A (4). Ansalactams B-D are significantly modified ansamycins, representing three new carbon skeletons and further illustrating the biosynthetic plasticity of the ansalactam class. Unlike ansalactam A, ansalactams B and D are penta- and hexacyclic metabolites, while ansalactam C illustrates an open polyene chain with a terminal carboxylic acid.

The Halicylindramides, Farnesoid X Receptor Antagonizing Depsipeptides from a Petrosia sp. Marine Sponge Collected in Korea.

Three new structurally related depsipeptides, halicylindramides F-H (1-3), and two known halicylindramides were isolated from a Petrosia sp. marine sponge collected off the shore of Youngdeok-Gun, East Sea, Republic of Korea. Their planar structures were elucidated by extensive spectroscopic data analyses including 1D and 2D NMR data as well as MS data. The absolute configurations of halicylindramides F-H (1-3) were determined by Marfeys method in combination with Edman degradation. The absolute configurations at C-4 of the dioxyindolyl alanine (Dioia) residues of halicylindramides G (2) and H (3) were determined as 4S and 4R, respectively, based on ECD spectroscopy. The C-2 configurations of Dioia in 2 and 3 were speculated to both be 2R based on the shared biogenesis of the halicylindramides. Halicylindramides F (1), A (4), and C (5) showed human farnesoid X receptor (hFXR) antagonistic activities, but did not bind directly to hFXR.

Lodopyridones B and C from a marine sediment-derived bacterium Saccharomonospora sp.

HPLC-UV guided isolation of the culture broth of a marine bacterium Saccharomonospora sp. CNQ-490 has led to the isolation of two new natural products, lodopyridones B and C (1 and 2) along with the previously reported lodopyridone A (3). Their chemical structures were established from the interpretation of 2D NMR spectroscopic data and the comparison of NMR data with the lodopyridone A (3). Lodopyridones B and C (1 and 2) possess the thiazole, and chloroquinoline groups which are characteristic features of these molecules. Lodopyridones A-C show weak inhibitory activities on the β-site amyloid precursor protein cleaving enzyme 1 (BACE1).