Meng-Liang Wen

Naphthospironone A: An Unprecedented and Highly Functionalized Polycyclic Metabolite from an Alkaline Mine Waste Extremophile

Extremophiles, microorganisms surviving in various extreme environments, have developed unique defenses that either tolerate or favor extremes of pH, temperature, salinity, pressure and radiation. These special characteristics frequently lead to synthesis of novel molecules encompassing a variety of unusual structural classes with significant biological activities. In comparison with extremophiles from natural environments, microorganisms isolated from man-made extreme environments are emerging as a valuable resource for bioactive natural products. For example, Stierle and coworkers have recently isolated several novel molecules, including berkelic acid, which inhibits protein-cleaving enzymes caspase-1 and matrix metalloproteinase-3, from acidophilic fungi found in Berkeley Pit Lake (an abandoned copper mine filled with acidic water at pH 2.7). This implies that there are miniature natural product libraries to be found in the most unexpected places. Extremophiles surviving in man-made extreme environments around the world could be an untapped mine for drug discovery. Inspired by Stierle s work, we profiled the metabolite patterns of alkalophilic actinomycetes, which were isolated from an alkaline soil sample (pH 10) collected from the Datun tin mine tailings area (Yunnan province, Southwest China; 103818’36’ E, 23822’12’ N; formed by the materials remaining after extraction and beneficiation of tin ores over 50 years). The TLC and HPLC-DAD analysis of the acetone extract of Nocardiopsis sp. (YIM DT266) revealed the presence of a new metabolite, naphthospironone A (1, Scheme 1). The compound was obtained as a colorless solid (3 mgL ) by standard chromatographic procedures from solid fermentation (30 L) of the strain. Even though some structural elements resemble those of actinomycetes metabolites, such as a-naphthocyclinone (2) and b-naphthocycli-

Griseusins F and G, spiro-naphthoquinones from a tin mine tailings-derived alkalophilic Nocardiopsis species.

Griseusins F (1) and G (2), two 2a-hydro-8a-(2-oxopropyl)-substituted spiro-naphthoquinones with a previously undescribed C23 polyketide skeleton, were isolated from a Yunnan tin mine tailings-derived alkalophilic actinomycete, Nocardiopsis sp. YIM DT266. Their complete structure assignments with the absolute stereochemistry were elucidated by spectroscopic data, X-ray crystal diffraction, calculation of optical rotation, and CD spectroscopic analysis. Compounds 1 and 2 exhibited strong cytotoxicity (IC50 0.37-0.82 μM) and antibacterial activity (MIC 0.80-1.65 μg/mL) against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) in vitro.

Phenazinolins A-E: novel diphenazines from a tin mine tailings-derived Streptomyces species

Phenazinolins A-E (1-5), which possess a carbon skeleton unique to diphenazines (the azabicyclo[3.3.1]nonadienol moiety in 1-3 and the oxabicyclo[3.3.1]nonadienol moiety in 4 and 5), were isolated from tin mine tailings-derived Streptomyces diastaticus YIM DT26, with 1-3 exhibited appreciable cytotoxicity and antibiotic effects.

Genome Sequence of Streptomyces auratus Strain AGR0001, a Phoslactomycin-Producing Actinomycete

Streptomyces auratus strain AGR0001 produces neophoslactomycin A, a novel analog of phoslactomycin that possesses potent activity against some phytopathogenic fungi. Here, the draft genome sequence of S. auratus strain AGR0001 is presented, which would provide insight into the biosynthetic mechanism of neophoslactomycin A.

A new isoflavone derivative from Streptomyces sp. YIM GS3536

A new natural product named 7-O-methyl-8-chlorogenistein (1) was isolated together with eight known isoflavones, 8-chlorogenistein (2), kakkatin (3), 7-O-methyl genistein (4), genistein (5), daidzein (6), glycitin (7), genistin (8), and daidzin (9), from the metabolites of Streptomyces strain YIM GS3536, which was isolated from soil sample collected from Yunnan Province, China. We report the unambiguous assignments of the 1H and 13C NMR spectra of the new compound 7-O-methyl-8-chlorogenistein (1). Compound 1 exhibited appreciable cytotoxicity against human melanoma cell lines (B16) and human leukemia cell lines (HL60) with IC50 values of 17.5 and 19.2 μM, respectively. The MIC values of 1 for Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Candida albicans were in the range of 23–35 μM.

A novel phenylspirodrimane dimer from cultures of the fungus Stachybotrys chartarum

Abstract Stachartone A (1), a novel phenylspirodrimane dimer, was isolated from cultures of the tin mine tailings-associated fungus Stachybotrys chartarum. Its structure was elucidated by means of spectroscopic methods. At the same time, compound (1) was tested for its cytotoxicity against five human cancer cell lines.

A new phenylspirodrimane dimer from the fungus Stachybotrys chartarum

A new phenylspirodrimane dimer, named stachartarin A (1), was isolated from cultures of the tin mine tailings-associated fungus Stachybotrys chartarum. Its structures were elucidated by means of spectroscopic methods. At the same time, the compound was tested for its cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7, and SW480 cells.

A new pregnane steroid from cultures of Aspergillus versicolor

Abstract A new pregnane steroid, named aspergillon A (1), together with two known compounds, (22E,24R)-ergosta-5,7,22-trien-3β-ol (2) and (22E, 24R)-ergosta-4,6,8(14),22-tetraen-3-one (3) were isolated from cultures of the tin mine tailings-associated fungus Aspergillus versicolor. The new structure and absolute configuration were determined with the help of extensive spectroscopic analyses and quantum chemical calculations of the electronic circular dichroism (ECD) spectra.

A New Dichlorinated Aromatic Lactone from the Tin Mine Tailings-Derived Fungus Torula sp. YIM DT 10072

One rare dichlorinated aromatic lactone was isolated from the tin mine tailings-derived fungus Torula sp. YIM DT 10072. Its structure was determined by detailed analysis of spectroscopic data including 1H NMR, 13C NMR, 2D NMR, and HR-FAB-MS. The compound showed antibacterial activity against Staphylococcus aureus with MIC value of 64 μg/mL.