Xinpeng Tian

Antimalarial β-carboline and indolactam alkaloids from Marinactinospora thermotolerans, a deep sea isolate.

Four new β-carboline alkaloids, designated marinacarbolines A-D (1-4), two new indolactam alkaloids, 13-N-demethyl-methylpendolmycin (5) and methylpendolmycin-14-O-α-glucoside (6), and the three known compounds 1-acetyl-β-carboline (7), methylpendolmycin (8), and pendolmycin (9) were obtained from the fermentation broth of Marinactinospora thermotolerans SCSIO 00652, a new actinomycete belonging to the family Nocardiopsaceae. Their structures were elucidated by extensive MS and 1D and 2D NMR spectroscopic data analyses. The structure of compound 1 was further confirmed by single-crystal X-ray crystallography. The new compounds 1-6 were inactive against a panel of eight tumor cell lines (IC50>50 μM) but exhibited antiplasmodial activities against Plasmodium falciparum lines 3D7 and Dd2, with IC50 values ranging from 1.92 to 36.03 μM.

Spiroindimicins A-D: new bisindole alkaloids from a deep-sea-derived actinomycete.

A PCR-based screening approach led to the identification of a deep-sea-derived Streptomyces sp. SCSIO 03032 capable of producing new bisindole alkaloids spiroindimicins A-D (1-4). Structural elucidation of these compounds revealed the presence of unusual [5,6] or [5,5] spiro-ring containing skeletons. Spiroindimicins B-D (2-4) with a [5,5] spiro-ring exhibited moderate cytotoxicities against several cancer cell lines.

Sciscionella marina gen. nov., sp. nov., a marine actinomycete isolated from a sediment in the northern South China Sea

The taxonomic position of an actinomycete, designated SCSIO 00231(T), isolated from a sediment sample collected from the northern South China Sea, was determined by using a polyphasic approach. The organism formed fragmented substrate hyphae and sparse aerial mycelium on modified ISP 2 medium. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain SCSIO 00231(T) fell into the family Pseudonocardiaceae, in which it formed a distinct lineage and was loosely associated with Thermocrispum municipale DSM 44069(T), with 93 % similarity. The other closest phylogenetic neighbours were Saccharopolyspora erythraea NRRL 2338(T) (92.6 % similarity) and Amycolatopsis sacchari DSM 44468(T) (93.1 % similarity). The isolate had cell-wall type IV (meso-diaminopimelic acid and whole-cell sugars arabinose, galactose and glucose) and phospholipid type III. The predominant menaquinone was MK-9(H(4)). The G+C content of the genomic DNA was 69 mol%. Based on these data, strain SCSIO 00231(T) can be readily distinguished from previously described organisms and represents a new genus within the family Pseudonocardiaceae. The name Sciscionella gen. nov. is proposed, with the novel species Sciscionella marina sp. nov. The type strain of Sciscionella marina is SCSIO 00231(T) (=KCTC 19433(T) =CCTCC AA208009(T)).

Identification and Characterization of Xiamycin A and Oxiamycin Gene Cluster Reveals an Oxidative Cyclization Strategy Tailoring Indolosesquiterpene Biosynthesis

Xiamycin A (XMA) and oxiamycin (OXM) are bacterial indolosesquiterpenes featuring rare pentacyclic ring systems and are isolated from a marine-derived Streptomyces sp. SCSIO 02999. The putative biosynthetic gene cluster for XMA/OXM was identified by a partial genome sequencing approach. Eighteen genes were proposed to be involved in XMA/OXM biosynthesis, including five genes for terpene synthesis via a non-mevalonate pathway, eight genes encoding oxidoreductases, and five genes for regulation and resistance. Targeted disruptions of 13 genes within the xia gene cluster were carried out to probe their encoded functions in XMA/OXM biosynthesis. The disruption of xiaK, encoding an aromatic ring hydroxylase, led to a mutant producing indosespene and a minor amount of XMA. Feeding of indosespene to XMA/OXM nonproducing mutants revealed indosespene as a common precursor for XMA/OXM biosynthesis. Most notably, the flavin dependent oxygenase XiaI was biochemically characterized in vitro to convert indosespene to XMA, revealing an unusual oxidative cyclization strategy tailoring indolosesquiterpene biosynthesis.

Haloactinospora alba gen. nov., sp. nov., a halophilic filamentous actinomycete of the family Nocardiopsaceae

A novel halophilic, filamentous, actinomycete strain, designated YIM 90648(T), was isolated from a salt lake in Xinjiang Province, north-west China, and subjected to a polyphasic taxonomic study. Optimal growth occurred at 37 degrees C, pH 7.0-8.0 and 15% (w/v) NaCl. The aerial mycelium of strain YIM 90648(T) formed long chains of spores at maturity and the spores were cylindrical with smooth surfaces. Spore chains with pseudosporangia at the end were borne on the substrate mycelium and most spores had wrinkled surfaces. Strain YIM 90648(T) contained meso-diaminopimelic acid as the diagnostic diamino acid and galactose and ribose as the major whole-cell components. The phospholipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine and phosphatidylinositol mannoside. MK-10(H(8)), MK-11(H(4)), MK-11(H(6)) and MK-11(H(8)) were the predominant menaquinones. The major fatty acids were i-C(16:0) and ai-C(17:0). The DNA G+C content was 68 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain YIM 90648(T) formed a distinct lineage within the family Nocardiopsaceae and showed 16S rRNA gene sequence similarity of 93.3-95.0% with members of the family Nocardiopsaceae. On the basis of the polyphasic evidence, a novel genus and species, Haloactinospora alba gen. nov., sp. nov., is proposed to accommodate this isolate. The type strain of Haloactinospora alba is YIM 90648(T) (=DSM 45015(T) =CCTCC AA 206008(T)).

Marthiapeptide A, an Anti-infective and Cytotoxic Polythiazole Cyclopeptide from a 60 L Scale Fermentation of the Deep Sea-Derived Marinactinospora thermotolerans SCSIO 00652

A new sequential tristhiazole-thiazoline-containing cyclic peptide, marthiapeptide A (1), was isolated from a 60 L scale culture of the deep South China Sea-derived strain Marinactinospora thermotolerans SCSIO 00652. The planar structure and absolute configuration of 1 were elucidated by application of spectroscopic techniques, as well as by single-crystal X-ray diffraction and chiral-phase HPLC analysis of the acid hydrolysates. Marthiapeptide A (1) exhibited antibacterial activity against a panel of Gram-positive bacteria, with MIC values ranging from 2.0 to 8.0 μg/mL, and displayed strong cytotoxic activity against a panel of human cancer cell lines with IC(50) values ranging from 0.38 to 0.52 μM.

Marinactinospora thermotolerans gen. nov., sp. nov., a marine actinomycete isolated from a sediment in the northern South China Sea

A novel marine actinomycete, designated SCSIO 00652(T), was isolated from a marine sediment collected from the northern South China Sea at a depth of 3865 m. The strain formed branched substrate mycelia and no fragmentation was found. Abundant aerial mycelia differentiated into long spore chains and the spores had a wrinkled surface. Growth occurred on ISP medium 2 with 0-5 % (w/v) NaCl and at 10-55 degrees C. The whole-cell hydrolysate contained meso-diaminopimelic acid and glucose as the whole-cell sugar. blast search results based on an almost-complete 16S rRNA gene sequence showed the novel strain had the highest similarity (96.5 %) with Nocardiopsis trehalosi VKM Ac-942(T). The phylogenetic tree of the family Nocardiopsaceae indicated that strain SCSIO 00652(T) formed a distinct lineage at the deepest branch with a high bootstrap value. Additionally, the profiles of menaquinones, phospholipids and fatty acids showed there were marked differences between strain SCSIO 00652(T) and the recognized genera of the family Nocardiopsaceae. Based on the polyphasic data, a new genus, Marinactinospora gen. nov., is proposed within the family Nocardiopsaceae with the type species Marinactinospora thermotolerans sp. nov. The type strain of the type species is SCSIO 00652(T) (=DSM 45154(T)=CCTCC AA 208041(T)).

Pseudonocardians A-C, new diazaanthraquinone derivatives from a deap-sea actinomycete Pseudonocardia sp. SCSIO 01299.

Pseudonocardians A–C (2–4), three new diazaanthraquinone derivatives, along with a previously synthesized compound deoxynyboquinone (1), were produced by the strain SCSIO 01299, a marine actinomycete member of the genus Pseudonocardia, isolated from deep-sea sediment of the South China Sea. The structures of compounds 1–4 were determined by mass spectrometry and NMR experiments (1H, 13C, HSQC, and HMBC). The structure of compound 1, which was obtained for the first time from a natural source, was confirmed by X-ray analysis. Compounds 1–3 exhibited potent cytotoxic activities against three tumor cell lines of SF-268, MCF-7 and NCI-H460 with IC50 values between 0.01 and 0.21 μm, and also showed antibacterial activities on Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212 and Bacillus thuringensis SCSIO BT01, with MIC values of 1–4 μg mL−1.

Lobophorins E and F, new spirotetronate antibiotics from a South China Sea-derived Streptomyces sp. SCSIO 01127

The strain SCSIO 01127, isolated from the South China Sea sediment, was identified as a member of Streptomyces by the 16S rDNA sequence analysis. Two new spirotetronate antibiotics lobophorins E (1) and F (2), along with two known analogs lobophorins A (3) and B (4), were isolated from Streptomyces sp. SCSIO 01127. Their structures were elucidated on the basis of detailed IR, NMR and MS spectroscopic analyses. The new compound lobophorin F (2) showed antibacterial activities against Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 with MIC values of 8 μg ml−1 for both the strains, better than that of lobophorin B (4). Lobophorin F (2) also displayed better cytotoxic activities than lobophorin B (4), with IC50 of 6.82, 2.93 and 3.16 μM against SF-268, MCF-7 and NCI-H460, respectively.

Antiviral Merosesquiterpenoids Produced by the Antarctic Fungus Aspergillus ochraceopetaliformis SCSIO 05702

Five new highly oxygenated α-pyrone merosesquiterpenoids, ochraceopones A-E (1-5), together with one new double bond isomer of asteltoxin, isoasteltoxin (6), and two known asteltoxin derivatives, asteltoxin (7) and asteltoxin B (8), were isolated from an Antarctic soil-derived fungus, Aspergillus ochraceopetaliformis SCSIO 05702. Their structures were determined through extensive spectroscopic analysis, CD spectra, quantum mechanical calculations, and X-ray single-crystal diffraction. Ochraceopones A-D (1-4) are the first examples of α-pyrone merosesquiterpenoids possessing a linear tetracyclic carbon skeleton, which has not been previously described. All the isolated compounds were tested for their antiviral, cytotoxic, antibacterial, and antitubercular activities. Among these compounds, ochraceopone A (1), isoasteltoxin (6), and asteltoxin (7) exhibited antiviral activities against the H1N1 and H3N2 influenza viruses with IC50 values of >20.0/12.2 ± 4.10, 0.23 ± 0.05/0.66 ± 0.09, and 0.54 ± 0.06/0.84 ± 0.02 μM, respectively. A possible biosynthetic pathway for ochraceopones A-E (1-5) was proposed.