Two new aromatic tenvermectins from mutant Streptomyces avermitilis HU02-06.

Two new aromatic tenvermectins (TVMs), 13-oleandrosyl-oleandrosyloxy ST906 (1) and aromatic TVM B (2), were isolated from the fermentation broth of Streptomyces avermitilis HU02-06. Their structures were established by extensive spectroscopic analysis, including 1D and 2D NMR and HRESIMS data. Bioassay test showed that these two new tenvermectins exhibited weak nematocidal activity against Bursaphelenchus xylophilus and moderate cytotoxic activity against tumor cell lines HepG2 and HCT116.

Anulamycins A-F, Cinnamoyl-Containing Peptides from a Lake Sediment Derived Streptomyces.

Bioinformatics analysis of a whole genome sequence coupled with HPLC-DAD analysis revealed that Streptomyces sp. Hu103 has the capacity to produce skyllamycin analogues. A subsequent chemical investigation of this strain yielded four new cinnamoyl-containing cyclopeptides, anulamycins A-D (1-4), two new cinnamoyl-containing linear peptides, anulamycins E and F (5 and 6), and two known cyclopeptides, skyllamycins A (7) and B (8). Their structures including absolute configurations were elucidated by detailed analysis of NMR and HRESIMS/MS spectroscopic data and the advanced Marfey's method. Compounds 1-4 exhibited antibacterial activity comparable to those of skyllamycins A and B.

A new ß-class milbemycin derivative from a mutant of genetically engineered strain Streptomyces avermitilis AVE-H39.

A new ß-class milbemycin, 13α-hydroxy milbemycin ß6 (1), was isolated from the fermentation broth of a mutant of genetically engineered strain Streptomyces avermitilis AVE-H39. Its structure and absolute configuration were elucidated by extensive spectroscopic methods and confirmed by single crystal X-ray diffraction.

A novel spiro-heterocycle milbemycin metabolite from a genetically engineered strain of Streptomyces bingchenggensis.

Milbemycin R, a novel spiro-heterocycle milbemycin, was obtained from the metabolites produced by the mutant strain S. bingchenggensis BCJ60B11. Its structure was determined by spectroscopic and spectrometric analyses including 1 D, 2 D NMR, IR, HR-ESI-MS data. The acaricidal and nematicidal activities of milbemycin R against Tetranychus cinnabarinus and Bursaphelenchus xylophilus were tested. Milbemycin R possessed better acaricidal activity than milbemycins A3/A4.

Sarubicinols A-C, Cytotoxic Benzoxazoles from a Streptomyces.

A chemical investigation of Streptomyces sp. Hu186 afforded two known quinone antibiotics, sarubicin A (1) and sarubicin B (2), together with three unusual variants, sarubicinols A-C (3-5), and two new 1,4-naphthoquinone metabolites, sarubicin B1 (6) and sarubicin B2 (7). Compounds 3-5 possess a rare 2-oxabicyclo [2.2.2] substructure and a benzoxazole ring system. Their structures were elucidated using 1D and 2D nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry data. The absolute configurations of the side-chain moieties in 4 and 5 were solved by electronic circular dichroism calculations. Compounds 1-7 showed moderate cytotoxic activity against four tumor cell lines.

Two new cyclopentenone metabolites from Streptomyces sp. HU119.

Two previously undescribed cyclopentenone metabolites, (S)-2-(3-acetylamino-2-methyl)propyl-3-butyl-2-cyclopenten-1-one (1) and (S)-2-(3-acetylamino-2-ethyl)propyl-3-butyl-2-cyclopenten-1-one (2), were isolated from the fermentation broth of the strain Streptomyces sp. HU119. The structures of 1 and 2 were determined by the comprehensive spectroscopic analysis, including 1 D, 2 D NMR, MS spectral analysis and the comparison with data from the literature. The absolute configurations were elucidated by experimental and calculated optical rotations (OR). Compounds 1 and 2 displayed weak cytotoxic activity.

A facile preparation and crystal structure of romipeptide A.

A double disulfide tethering depsipeptide dimer, romipeptide A (1) was prepared by NaOH catalyzed dimerization of romidepsin. Its structure was determined by analysis of NMR and HR-ESI-MS data as well as single crystal X-ray diffraction. Bioassay results showed that 1 exhibited good cytotoxic activity against two tumor cell lines B16 and HCT116. This study reported the single crystal data of 1 for the first time. The facile preparation of 1 afforded enough amount for its further biological evaluations.

Two new 13-hydroxylated milbemycin metabolites from the genetically engineered strain Streptomyces avermitilis AVE-H39.

Two new milbemycin metabolites, 13α-hydroxymilbemycin ß13 (1) and 26-methyl-13α-hydroxymilbemycin ß13 (2), were isolated from the fermentation broth of a genetically engineered strain Streptomyces avermitilis AVE-H39. Their structures were determined by the comprehensive spectroscopic data, including 1 D, 2 D NMR, MS spectral analysis and the comparison with data from the literature. Compounds 1 and 2 not only exhibited potent acaricidal activities against Tetranychus cinnabarinus, but also had nematocidal activity against Bursaphelenchus xylophilus.

Two new milbemycin derivatives from a genetically engineered strain Streptomyces bingchenggensis.

Two new milbemycin derivatives, milbemycin M (1) and milbemycin N (2), were isolated from the culture of a genetically engineered strain Streptomyces bingchenggensis BCJ60. Their structures were elucidated through the interpretation of NMR and HR-ESI-MS spectroscopic data, as well as comparison with previous reports. The acaricidal and nematicidal activities of them against Tetranychus cinnabarinus and Bursaphelenchus xylophilus were tested. The results showed that compounds 1-2 possessed potent acaricidal and nematocidal activities.

Two novel milbemycin derivatives from the genetically engineered strain Streptomyces avermitilis AVE-H39.

Two novel milbemycin derivatives, 5,27-epoxy-13α-hydroxy milbemycin ß11 (1) and 5,27-epoxy-13α-hydroxy-25-ethyl milbemycin ß11 (2), were isolated from the genetically engineered strain Streptomyces avermitilis AVE-H39. Their structures were elucidated through the interpretation of HR-ESIMS and extensive NMR spectroscopic data. Compounds 1 and 2 exhibited moderate acaricidal and nematicidal activities.

Two new compounds from Streptomyces sp. HS-NF-813.

Two new derivatives of cytotoxic substance BE-52211, designed as BE-52211D (1) and BE-52211E (2), were isolated from the fermentation broth of the strain Streptomyces sp. HS-NF-813. Their structures were determined by 1D and 2D NMR techniques, ESI-MS and comparison with data from the literature. The absolute stereochemistry of 1 was elucidated by NMR data of the Mosher ester derivatives. Compounds 1 and 2 showed moderate cytotoxic activity against three human tumor cell lines.

Two new glutarimide antibiotics from Streptomyces sp. HS-NF-780.

Two new glutarimide antibiotics, 9-methylstreptimidone 2-α-D-glucopyranoside (1), and hydroxyiso-9-methylstreptimidone (2), along with a known compound, 9-methylstreptimidone (3), have been isolated from the broth of Streptomyces sp. HS-NF-780. Their structures were determined on the basis of spectroscopic analysis, including 1D and 2D NMR techniques as well as ESI-MS and comparison with data from the literature. By modified Mosher's method and acid hydrolysis, the absolute configurations of compounds 1 and 2 were established. Compounds 1 and 2 exhibited moderate cytotoxic activity.

Bioactive naphthoquinone and anthrone derivatives from endophytic Micromonospora sp. NEAU-gq13.

Two new naphthalenone derivatives, 5-hydroxy-4-oxo-2-(2-oxopropyl)-1,2,3,4-tetrahydronaphthalen-1-yl acetate (1) and 5-hydroxy-2-(2-hydroxypropyl)naphthalene-1,4-dione (2), together with two new anthrone derivatives, (S)-2,5-dihydroxy-2-methyl-1,2,3,4-tetrahydroanthracene-9,10-dione (3) and 4,5-dihydroxy-2-methyl-9H-xanthen-9-one (4), were isolated from the fermentation broth of endophytic Micromonospora sp. NEAU-gq13. Their structures were determined by 1D-NMR, 2D-NMR, and HR-ESI-MS analysis. Compounds 2 and 3 exhibited strong cytotoxic activity against human central nervous system cancer (SF-268) with the IC50 values of 3.04 and 5.66 µg/ml, respectively. Moreover, compound 2 also displayed potent activity against human liver cancer (HepG2) with an IC50 value of 1.01 µg/ml.

Characterization of the N-methyltransferases involved in the biosynthesis of toxoflavin, fervenulin and reumycin from Streptomyces hiroshimensis ATCC53615.

Toxoflavin (1), fervenulin (2), and reumycin (3), known to be produced by plant pathogen Burkholderia glumae BGR1, are structurally related 7-azapteridine antibiotics. Previous biosynthetic studies revealed that N-methyltransferase ToxA from B. glumae BGR1 catalyzed the sequential methylation at N6 and N1 in pyrimido[5,4-e]-as-triazine-5,7(6H,8H)-dione (4) to generate 1. However, the N8 methylation of 4 in the biosynthesis of fervenulin remains unclear. To explore the N-methyltransferases required for the biosynthesis of 1 and 2, we identified and characterized the fervenulin and toxoflavin biosynthetic gene clusters in S. hiroshimensis ATCC53615. On the basis of the structures of intermediates accumulated from the four N-methyltransferase gene inactivation mutants and systematic enzymatic methylation reactions, the tailoring steps for the methylation order in the biosynthesis of 1 and 2 were proposed. The N-methylation order and routes for the biosynthesis of fervenulin and toxoflavin in S. hiroshimensis are more complex and represent an obvious departure from those in B. glumae BGR1.

Two new lankacidin-related metabolites from Streptomyces sp. HS-NF-1178.

Two new lankacidin-related metabolites, 2,18-seco-lankacidinol A (1), 2,18-seco-lankacidinol B (2) and a known compound, lankacidinol (3), were isolated from the fermentation broth of Streptomyces sp. HS-NF-1178. Their structures were determined on the basis of spectroscopic analysis, including 1D and 2D NMR techniques as well as ESI-MS and comparison with data from the literature. These two new compounds, especially compound 1, exhibited potent antitumor activity.

A new anthracycline-type metabolite from Streptomyces sp. NEAU-L3.

A new anthracycline-type metabolite, designated as tetracenoquinocin A (1), was isolated from the fermentation broth of Streptomyces sp. NEAU-L3. Its structure was determined on the basis of spectroscopic analysis, including 1D and 2D NMR techniques as well as ESI-MS and comparison with data from the literature. Compound 1 showed potent cytotoxic activity against three cancer cell lines (HepG2, A549, HCT-116) with IC50 values of 5.57, 24.30 and 20.82 µM, respectively.

A new naphthalenepropanoic acid analog from the marine-derived actinomycetes Micromonospora sp. HS-HM-036.

A new naphthalenepropanoic acid analog (1) was isolated from the broth of the actinomycetes Micromonospora sp. HS-HM-036. The structure of compound 1 was determined based on MS and extensive NMR analysis. A preliminary investigation of the biological activity of compound 1 was also described.

A new spectinabilin derivative with cytotoxic activity from ant-derived Streptomyces sp. 1H-GS5.

A new spectinabilin derivative (1) was isolated from the fermentation broth of the ant-derived Streptomyces sp. 1H-GS5, and the structure was elucidated by extensive spectroscopic analysis. Compound 1 showed cytotoxicity against human tumor cell lines A549, HCT-116, and HepG2 with IC50 values of 9.7, 12.8, and 9.1 µg/ml, respectively, which was relative higher than that of spectinabilin.

New macrocyclic lactones with acaricidal and nematocidal activities from a genetically engineered strain Streptomyces bingchenggensis BCJ60.

Two new macrocyclic lactones, 4,25-diethyl-4,25-demethyl-milbemycin ß3 (1) and 27-formaldehyde-milbemycin ß14 (2), were isolated from a genetically engineered strain Streptomyces bingchenggensis BCJ60. Their structures were determined on the basis of spectroscopic analysis, including 1D and 2D NMR techniques as well as ESI-MS and comparison with data from the literature. The acaricidal and nematocidal capacities of compounds 1 and 2 were evaluated against Tetranychus cinnabarinus and Bursaphelenchus xylophilus, respectively. The results showed that the two new macrocyclic lactones 1 and 2 possessed potent acaricidal and nematocidal activities.