FR207944, an antifungal antibiotic from Chaetomium sp. no. 217 I. Taxonomy, fermentation, and biological properties

An antifungal antibiotic, FR207944, was isolated from the culture broth of a fungal strain Chaetomium sp. no. 217. FR207944 is a triterpene glucoside with antifungal activity against Aspergillus fumigatus and Candida albicans. Specifically, FR207944 exhibits in vitro and in vivo antifungal activity against A. fumigatus. The effects of FR207944 on the morphology of A. fumigatus were shown to be similar to those of FR901379, a known 1,3-beta-glucan synthase inhibitor. The MECs of FR207944 against A. fumigatus FP1305 and C. albicans FP633 in micro-broth dilution test were 0.039 and 1.6 mug/ml respectively. FR207944 showed good potency by subcutaneous injection and oral administration against A. fumigatus in a murine systemic infection model, with ED(50)s of 5.7 and 17 mg/kg respectively.     

Isolation and structure elucidation of a new antifungal and antibacterial antibiotic produced by Streptomyces sp. 201

An antibacterial and antifungal antibiotic was isolated from the culture filtrate of Streptomyces sp. 201, and its structure was determined as 2-methyl-heptyl isonicotinate by extensive use of NMR spectroscopy. The compound exhibited marked antimicrobial activity against Bacillus subtilis, Shigella sp., Klebsiella sp., E. coli, Proteus mirabilis, and the pathogenic fungi, Fusarium moniliforme, F. semitectum, F. oxysporum, F. solani and Rhizoctonia solani.     

Isolation and structure elucidation of parnafungins C and D,isoxazolidinone-containing antifungal natural products

Parnafungins, natural products containing an isoxazolidinone ring, have been isolated from Fusarium larvarum and have been shown to be potent inhibitors of the fungal polyadenosine polymerase. The extraction and analysis of fermentation broths of taxonomically related organisms identified as closely related Fusarium spp. produce not only parnafungin A and B, but also significant quantities of two related components. These members of the paranfungin family of natural products have been isolated and the structure of each has been elucidated. While structurally analogous to parnafungin A, parnafungin C is further elaborated by methylation of a phenolic hydroxyl group, and parnafungin D has both the methyl phenol ether as well as an epoxide in the xanthone ring system. Parnafungin C and D have potent, broad spectrum antifungal activity and also have been shown to target fungal mRNA cleavage and polyadenylation.     

Isolation of a Paenibacillus sp. strain and structural elucidation of its broad-spectrum lipopeptide antibiotic

This research was initiated to search for novel antimicrobial compounds produced by food or environmental microorganisms. A new bacterial strain, designated OSY-SE, which produces a unique and potent antimicrobial agent was isolated from soil. The isolate was identified as a Paenibacillus sp. through cultural, biochemical, and genetic analyses. An antimicrobial compound was extracted from Paenibacillus OSY-SE with acetonitrile and purified using liquid chromatography. After analyses by mass spectrometry (MS) and nuclear magnetic resonance (NMR), the antimicrobial compound was determined to be a cyclic lipopeptide consisting of a C(15) fatty acyl (FA) chain and 13 amino acids. The deduced sequence is FA-Orn-Val-Thr-Orn-Ser-Val-Lys-Ser-Ile-Pro-Val-Lys-Ile. The carboxyl-terminal Ile is connected to Thr by ester linkage. The new compound, designated paenibacterin, showed antagonistic activities against most Gram-positive and Gram-negative bacteria tested, including Listeria monocytogenes, methicillin-resistant Staphylococcus aureus, Escherichia coli O157:H7, and Salmonella enterica serovar Typhimurium. Paenibacterin is resistant to trypsin, lipase, α-glucosidase, and lysozyme. Its antimicrobial activity was lost after digestion by pronase and polymyxin acylase. Paenibacterin is readily soluble in water and fairly stable to exposure to heat and a wide range of pH values. The new isolate and its antimicrobial agent are being investigated for usefulness in food and medical applications.     

Isolation, structure elucidation and biological activity of metabolites from Sch-642305-producing endophytic fungus Phomopsis sp. CMU-LMA

Eight polyketide compounds were isolated from the cultivation broth of Phomopsis sp. CMU-LMA. We have recently described LMA-P1, a bicyclic 10-membered macrolide, obtained as a bioconversion derivative of Sch-642305, the major compound isolated in this study. Benquinol is the ethyl ester derivative of the 13-dihydroxytetradeca-2,4,8-trienoic acid produced by Valsa ambiens. This compound is concomitantly produced with the 6,13-dihydroxytetradeca-2,4,8-trienoic acid (DHTTA) previously isolated from Mycosphaerellarubella. The absolute configuration of the new compound, (2R,3R,4S,5R)-3-hydroxy-2,4-dimethyl-5-[(S,Z)-3-methylpentenyl]-tetrahydro-pyranone LMA-P2 was confirmed by X-ray crystallography. The δ-lactone 2,3-dihydroxytetradecan-5-olide (DHTO) was previously isolated from Seiridium unicorne. This compound may form through the cyclization of the methyl-2,3,5-trihydroxytridecanoate LMA-P3, a new linear polyketide isolated in this study. Benquoine, a new 14-membered lactone generated from the cyclization of benquinol, is proposed as the key precursor for the biosynthesis of Sch-642305. Antimicrobial activity and cancer cell viability inhibition by the new compounds were investigated. Benquoine exhibits antimicrobial activity against Gram positive bacteria, and cytotoxicity against HCT-116 cancer cell line.     

Cytotoxic labdane alkaloids from an ascidian Lissoclinum sp.: isolation, structure elucidation, and structure-activity relationship

Four labdane alkaloids, haterumaimides N-Q (1-4), were isolated from an ascidian Lissoclinum sp. and their structures were elucidated by chemical and spectral analyses. Investigation of the structure-activity relationships of haterumaimides J-K, N-Q, and 14 related compounds suggested that the presence of hydroxyl groups at C-6, C-7, C-12, and C-18, a chlorine atom at C-2, and an imido NH in ring C should be essential for cytotoxicity against P388 cells.     

Isolation and structure elucidation of an alpha-amylase inhibitor, AI-3688, from Streptomyces aureofaciens

A novel polypeptide inhibitor, AI-3688, which acts upon human pancreatic alpha-amylase, was isolated from fermentation broth of Streptomyces aureofaciens. The purified peptide contains no unusual amino acids. Its Mr is 3936. The primary structure of AI-3688 was elucidated by automatic Edman degradation of the native or modified inhibitor. Two intramolecular cysteines form a disulphide bridge, thus creating a ring structure consisting of 17 amino acids. Strong sequence homology also exists to another microbial alpha-amylase inhibitor, tendamistat (HOE 467). This paper discusses the role of a common partial sequence, -Gln-Ser-Trp-Arg-Tyr-, present in the loop of both inhibitors as the active site of microbial peptide alpha-amylase inhibitors.     

一株毛壳霉属真菌中新结构活性聚酮类化合物研究

采用硅胶、凝胶柱层析以及反相高效液相色谱等分离技术,从一株毛壳霉属真菌的固体发酵提取物中分离纯化了5个聚酮类化合物chaetomones A-E(1-5),其结构主要通过分析核磁共振数据确定。生物活性测试结果表明化合物5具有抗白色念珠菌Candida albicans(ATCC10231)的活性,其IC50为20.0μmol/L。     

Efficacy assessment of antifungal metabolites from Chaetomium globosum No.05, a new biocontrol agent,against Setosphaeria turcica

Northern corn leaf blight (NCLB), an important and potentially destructive corn foliar disease, is caused by Setosphaeria turcica. The intent of this study was to evaluate antifungal metabolites from Chaetomium globosum (Cg) strain No.05 to suppress NCLB in maize. This strain significantly suppressed mycelial growth of numerous phytopathogenic fungi especially S. turcica on potato dextrose agar medium. The secondary metabolites of the strain inhibited mycelial growth and conidial germination of S. turcica. When co-inoculated at three droplets (5 μL/droplet) of conidial suspension (5 × 10⁴ conidia/mL) on each 8-cm-long detached leaf, 20% culture filtrates completely suppressed disease incidence of northern corn leaf blight. The application of the culture filtrates at 2 h post-inoculation (hpi) of S. turcica in greenhouse studies showed a 81.9% inhibition of NCLB on the seedlings, while culture filtrates applied before pathogen inoculation showed even higher rates of disease reduction. The application of the culture filtrates had no observed effects on the treated maize leaves or seedlings. Two active compounds, isolated from the extracts, were identified as chaetoglobosin A and chaetoglobosin C based on the spectroscopic analysis. Both in vitro and in planta bioassay experiments showed that chaetoglobosin A displayed potent biocontrol efficiency against S. turcica. To the best of our knowledge, this is the first report of the evaluation of the inhibitory effects of C. globosum and chaetoglobosin A against S. turcica both in vitro and on detached maize leaves.     

毛壳霉内切菊粉酶的纯化与性质

毛壳霉 (Chaetomiumsp .)C34发酵液经硫酸铵分级沉淀、DEAE 纤维素 11离子交换层析、Q SepharoseFastFlow离子交换层析、SephacrylS 2 0 0凝胶过滤、PhenolSepharoseTM HP疏水层析 ,得到电泳纯的内切菊粉酶组分 ,纯化倍数为 30 8倍 ,活力回收率为 7 7%。用SDS PAGE测得该酶亚基的分子量为 6 6kD。菊粉酶的最适pH为 6 0 ,最适温度为 5 0～ 5 5℃。菊粉酶在 5 0℃以下 ,pH5 0～ 8 0时较稳定。Cu2 完全抑制酶的活性 ,Mn2 、Zn2 、Fe2 、EDTA以及NBS(N bromosuccinimide ,N 溴代丁二酰亚胺 )对该酶有很强的抑制作用。该酶对菊粉有较强底物专一性 ,产物主要为低聚果糖 ,也可作用于蔗糖 ,I S值为 2 0。以菊粉为底物时 ,Km 为 0 199mmol L ,Vmax为 115 μmol (mg·min)。     

Isolation and structure elucidation of flavonoid glycosides from Solanum verbascifolium

Three flavonoid glycosides including a new one, 7,4′-dimethyl-apigenin-6-C-β-glucopyranosyl-2″-O-α-l-arabinopyranoside (1) were isolated from the leaves of Solanum verbascifolium (Solanaceae) through bioassay-guided isolation. The chemical structure of 1 was established on the basis of spectroscopic analysis. TRAIL-resistance-overcoming activity of 1 was evaluated.     

Isolation,biological properties,and spatial structure of an antibiotic loloatin A

Peptide antibiotic with cyanolytic activity was isolated from the IGM52 strain of the Brevibacillus laterosporus Gram-positive spore-forming bacteria. By 1H NMR spectroscopy, this antibiotic was identified as loloatin A, a cyclic decapeptide cyclo(-Asn-Asp-Tyr-Val-Orn-Leu-DTyr-Pro-Phe-DPhe-). The spatial structure of loloatin A in solution was determined. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2002, vol. 28, no. 4; see also http://www.maik.ru.     

Isolation,structure determination and cytotoxicity studies of tryptophan alkaloids from an Australian marine sponge Hyrtios sp.

Mass-guided fractionation of the MeOH extract from a specimen of the Australian marine sponge Hyrtios sp. resulted in the isolation of two new tryptophan alkaloids, 6-oxofascaplysin (2), and secofascaplysic acid (3), in addition to the known metabolites fascaplysin (1) and reticulatate (4). The structures of all molecules were determined following NMR and MS data analysis. Structural ambiguities in 2 were addressed through comparison of experimental and DFT-generated theoretical NMR spectral values. Compounds 1–4 were evaluated for their cytotoxicity against a prostate cancer cell line (LNCaP) and were shown to display IC₅₀ values ranging from 0.54 to 44.9 μM.     

Isolation, structure elucidation and biological activities of trichofumins A, B, C and D, new 11 and 13mer peptaibols from Trichoderma sp. HKI 0276W.

Trichofumins A-D were isolated from cultures of Trichoderma sp. HKI 0276 as new 11 and 13mer peptaibols. Similar to 15mer peptaibols they promote morphogenesis of the fungus Phoma destructiva and cause hypothermia in mice as a characteristic of neuroleptic activity. Membrane measurements using a synthetic BLM model showed that A, B, C and D increased membrane permeability for cations in a similar manner as was shown for larger peptaibols but with comparably lower efficiency.     

Antifungal Metabolites Produced by Chaetomium globosum No.04, an Endophytic Fungus Isolated from Ginkgo biloba

The fungal endophyte Chaetomium globosum No.04 was isolated from the medicinal plant Ginkgo biloba. The crude extract of the fungus fermentation were active in the agar-diffusion tests against the phytopathogenic fungi Rhizopus stolonifer and Coniothyrium diplodiella. Further bioassay-guided chemical investigation led to the isolation and purification of six alkaloids and three non-targeted compounds from 50 L fermentation of this endophytic fungus and their structures were elucidated as chaetoglobosin A, C, D, E, G, R (1-6), ergosterol, allantoin and uracil, by means of spectroscopic analysis. Compounds 1-6 showed significant growth inhibitory activity against R. stolonifer and C. diplodiella at a concentration of 20 μg/disc. We present here, for the first time, the potent antifungal activity of chaetoglobosins from endophytic fungi against two important phytopathogenic fungi R. stolonifer and C. diplodiella.     

Characterization of an antifungal chitinase from Bacillus sp.SL-13

Bacillus sp.SL-13 produced antifungal proteins.The growth of the plant-pathogenic fungi Rhizoctonia solani was considerably inhibited by the presence of the SL-13 culture supernatant.It is very suitable for the use in a relatively unstable environment,exhibiting effective biological control.     

Isolation, structure elucidation, preparation, and biological properties of neolambertellin

Neolambertellin (4), a novel biosynthetic congener of lambertellol and lambertellin, was isolated. The structure was confirmed by successful preparation from lambertellol A, which involves a rearrangement of spiro-butenolide moiety.