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Biosurfactants have been widely used in various industrial fields including medicine, food, cosmetics, detergent, pulp and paper, and oil and fat degradation. The culture broth of Aureobasidium pullulans A11211-4-57 using glucose as carbon source exhibited potent surfactant activity. The culture broth was separated by column chromatographies using ODS, silica gel, and Sephadex LH-20 resins, consecutively, to provide two biosurfactants. Based on mass and NMR measurements, their structures were determined as myo-inositol lipids and named pullusurfactans F and G. These compounds showed a high degree of activity, with 27.25 mN/m and 24.07 mN/m, respectively, at 1.0 mg lsup-1/sup, which is useful for washing and cleaning agents.

During the search for natural antioxidants from fungal metabolites, three new sesquiterpene derivatives (1-3) have been isolated from the culture broth of Coprinopsis echinospora. Their structures were determined by spectroscopic methods, mainly NMR and mass spectrometric analyses. These compounds exhibited antioxidant activity with IC

Two new meroterpene derivatives (1 and 2), together with three known compounds (3–5) were isolated from the culture broth of fungus Ganoderma oregonense. Chemical structures of compounds 1–5 were determined using spectroscopic methods. All compounds were tested for 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging efficacy. Compound 1 exhibited significant antioxidant activities with IC50 values of 31.2 and 65.4 μM in the ABTS and DPPH radical scavenging activities, respectively.

Three new meroterpenoids (1–3) together with one known compound (4) were isolated from the culture broth of Perenniporia medulla-panis, a wood-rotting fungus in the family Polyporaceae. Their structures were elucidated by NMR and HRESIMS analyses. These compounds exhibited antioxidant activity with IC50 values ranging from 12.8 to 190.3 μM in the 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical-scavenging assay.

In our effort to find antimicrobial agents from higher fungi, we isolated a new compound, dentipellin (1), along with three known glycosylated diterpenes, erinacines A-C (2-4) from culture broth of Dentipellis fragilis. Their chemical structures were determined by spectroscopic methods including NMR and mass measurements. These compounds exhibited weak antibacterial and antifungal activities.

In our effort to find antioxidants from the higher fungi, we isolated three new compounds (1–3) with a known compound, spirobenzofuran (4), from the culture broth of Hericium coralloides. Bioassay-guided fractionation led to the isolation of these compounds, and we determined the chemical structures through spectroscopic methods. These compounds exhibited antioxidant activity in the range of IC50 values of 29-66 μM in the 2,2’-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical-scavenging assay.

To discover antimicrobial agents from higher fungi, mannonerolidol (3), a new nerolidol mannoside, together with known schizostatin (1) and nerolidol (2) were isolated from an antimicrobial fraction of the culture broth of Schizophyllum commune. Structures of these compounds were determined through spectroscopic methods. Compounds 1 and 3 exhibited antimicrobial activities against plant pathogenic fungi Rhizoctonia solani, Diaporthe sp., Botrytis cinerea, and Alternaria solani and bacteria Bacillus subtilis and Staphylococcus aureus.

Two new sesquiterpenes (1 and 2) together with one known compound (3) were isolated from the culture broth of Coprinus rhizophorus. Chemical structures of these compounds were deduced by spectroscopic methods. Compound 1 exhibited free-radical-scavenging activity against the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical. Compounds 2 and 3 exhibited antimicrobial activities against Saccharomyces cerevisiae, Propionibacterium acnes, and Staphylococcus epidermidis.

Yeast biosurfactants have potent applications in medical, cosmeceutical, and food industries due to their specific modes of action, low toxicity, and applicability. In this study, biosurfactant-producing yeasts were screened for various industrial applications. Among them, Aureobasidium pullulans strain A11211-4-57 with potent surfactant activity from fleabane flower, Erigeron annus (L.) pers., was selected. From culture supernatant of strain A11211-4-57, five new low-surface-tension chemicals designated as pullusurfactans A–E were identified through consecutive chromatography steps, involving ODS, silica gel, Sephadex LH-20, and ODS Sep-pak cartridge columns. Based on mass and NMR measurements, structures of pullusurfactans A–E were determined as myo-inositol lipids with molecular formulae of C20H35O9, C18H32O8, C20H35O9, C24H42O9, and C18H32O8, respectively. These compounds exhibited potent biosurfactant activities (22.90, 22.40, 32.28, 25.28, and 22.44 mN/m, respectively). These results suggest that these novel biosurfactants have potential use as biosurfactants in industrial aspect.

Aureosurfactin and 3-deoxyaureosurfactin, novel biosurfactants produced by Aureobasidium pullulans L3-GPY

New p -terphenyls from the fruiting bodies of Pseudomerulius curtisii and their antioxidant activity

Members of the genera Phellinus and Inonotus, including P. linteus, P. igniarius, P. ribis, I. obliquus and I. xeranticus are well-known medicinal fungi (mushrooms) and have been used in treatment of cancer, diabetes, bacterial and viral infections and ulcer. Adverse effects of these medicinal mushrooms have not yet been reported, indicating the safe nature of these mushrooms. Polysaccharides, particularly β-glucan, are considered the compounds responsible for the biological activity of medicinal mushrooms. However, there is only a limited amount of evidence to indicate that polysaccharides are in fact responsible for the biological effects of these medicinal mushrooms. Recently, many research groups have begun identification of active low-MW compounds in medicinal mushrooms, with a focus on the yellow polyphenol pigments, which are composed of a styrylpyrone class of compounds. Interestingly, a representative group of medicinal fungi, including P. linteus, P. igniarius, P. ribis, I. obliquus and I. xeranticus were shown to produce a large and diverse range of styrylpyrone-type polyphenol pigments that exhibited various biological activities, including anti-oxidative, anti-inflammatory, cytotoxic, anti-platelet aggregation, anti-diabetic, anti-dementia and anti-viral effects. Styrylpyrone pigments in mushrooms are thought to have a role similar to that of flavonoids in plants. The unique and unprecedented carbon skeleton of fused styrylpyrone might be an attractive molecular scaffold for pharmacological applications. In this review, the structural diversity, biological effects and biogenesis of styrylpyrone-class polyphenols from medicinal fungi are described.

Novel styrylpyrones, phellinins A1 and A2, were isolated together with known styrylpyrone compounds, hispidin and 1,1-distyrylpyrylethan, from the cultured broth of Phellinus sp. KACC93057P. These compounds were purified by solvent partition, Sephadex LH-20 column chromatography, C(18)-solid phase extraction and finally by reversed-phase (ODS) TLC. To identify the phellinin producer Phellinus sp. KACC93057P, the ribosomal DNA (rDNA) internal transcribed space regions containing 5.8 rDNA were sequenced and compared with those of the known Phellinus isolates. Phellinus sp. KACC93057P was 94.8% identical to P. baumii and P. linteus, all of which did not produce phellinins A1 and A2. These compounds significantly scavenged free radicals such as 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) and superoxide.

Clitocybin A (1), a new antioxidant, was isolated from the culture broth of Clitocybe aurantiaca. This compound was purified by solvent extraction, silica gel column chromatography, Sephadex LH-20 column chromatography and preparative HPLC. Its structure was determined as 4,6-dihydroxy-2-ρ-hydroxyphenyl-isoindol-1-one on the basis of the UV, NMR, and MS spectroscopic analysis. The compound 1 showed potent free radical scavenging activity against superoxide, ABTS, and DPPH radicals, and protective effect against cellular DNA damage induced by oxidative stress.

Three new phenolic glycosides designated glyscavins A (1), B (2), and C (3) were isolated from the culture broth of a fungal strain Mycelia sterilia F020054. Structural elucidation of the compounds was based on the NMR and MS spectroscopic analyses. Glyscavins A, B and C exhibited higher free radical scavenging activity on superoxide and 2,2'-azinobis(3-ethylbenzothialozinesulfonic acid) cation radical (ABTS*+) than butylated hydroxyanisole (BHA).

New melanin synthesis inhibitors, melanocins A, B and C, were isolated from the fermentation broth and mycelium extract of Eupenicillium shearii F80695. Melanocin A, an isocyanide compound, inhibited mushroom tyrosinase and melanin biosynthesis of B16 melanoma cells with IC50 value of 9.0 nM and MIC value of 0.9 microM, respectively. Melanocin A also inhibited growth of Streptomyces bikiniensis. While, the structurally very related but non-isocyanide compounds melanocins B and C did not show inhibitory activity in these assays. Melanocins A, B and C showed potent antioxidant activity with scavenging activity of DPPH radical and superoxide anion radical.

Seven new peptaibols, atroviridins A-C composed of 20 residue amino acids and neoatroviridins A-D with 18 residues, were isolated from the culture broth of fungal strain F80317. The strain F80317 was identified as Trichoderma atroviride from its morphological and cultural characteristics. These compounds showed antimicrobial activity against Gram-positive bacteria and phytopathogenic fungi, and exhibited significant cytotoxicity to human cancer cell lines in vitro. Atroviridins showed significant membrane-perturbing activity responsible to their antibiotic action.

Oxidative stress caused by the disproportionate production of reactive oxygen species (free radicals), as compared with the elimination of these products by endogenous antioxidants, is considered to be one of the main causes in the progression of rheumatoid arthritis, arteriosclerosis, ischemic stroke, autoimmune disease, diabetes, cancer initiation and aging.1, 2, 3, 4, 5 Thus, an intake of natural antioxidants has been posited to reduce the risk of developing some of these pathologies related to oxidative stress.6 During a search for natural antioxidants from fungal strains, we found that the culture broth of Coprinus echinosporus exhibited potent free radical scavenging activity. C. echinosporus is a basidiomycete belonging to the genus Coprinus together with C. comatus, C. cinereus, C. plicatilis and C. radians. The genus Coprinus was reported to produce diverse sesquiterpenes, diterpenoids, triterpenoids and piperidine derivatives, which were reported to exhibit anti-inflammatory, antioxidant, anti-cancer, anti-bacterial, anti-fungal and cerebral blood flow-improving effects.7, 8, 9, 10, 11, 12 In this study, we report the isolation and structure determination of novel sesquiterpenes (2–4, Figure 1) and their antioxidant properties.

Glutamate, an excitatory amino acid, is known to induce neurotoxicity in central nervous system under abnormal conditions such as ischemia, hypoglycemia, epilepsy, Huntington's chorea, Parkinson's disease and Alzheimer's disease. In our search for neuroprotective agents of microbial origin against excitatory neurotoxins, we have isolated two new bicyclohexapeptides, neuroprotectins A and B, together with a known compound complestatin, from the fermentation broth of Streptomyces sp. Q27107. Neuroprotectins protected primary cultured chick telencephalic neurons from glutamate- and kainate-induced excitotoxicities in a dose-dependant fashion.

In our continuous investigation for free radical scavengers from extracts of fruit body of basidiomycetes, we have isolated four new p-terphenyl compounds, designated as curtisians A-D, from the methanolic extract of the fruit body of Paxillus curtisii. These compounds were isolated by silica gel and Sephadex LH-20 column chromatographies, preparative-TLC and HPLC, consecutively. The structures of curtisians were assigned as p-terphenyls with substituents of acetyl, benzoyl, phenylbutyryl, 3-hydroxybutyryl and 3-acetoxybutyryl. Curtisians A, B, C and D exhibited inhibitory activity against lipid peroxidation with IC50, values of 0.15, 0.17, 0.24 and 0.14 microg/ml, respectively.

Chaetoatrosin A, a novel chitin synthase II inhibitor, was isolated from the culture broth of fungus F449, which was identified as Chaetomium atrobrunneum F449. Chaetoatrosin A was purified by solvent partition, silica gel, ODS, preparative TLC, and Sephadex LH-20 column chromatographies, consecutively. The structure of chaetoatrosin A was assigned as 1,8-dihydroxy-3(2-hydroxypropionyl)-6-methoxynaphthalene on the basis of various spectroscopic analyses including UV, IR, mass spectral, and NMR. Its molecular weight and formula were found to be 262 and C 14 H 14 O 5 , respectively. Chaetoatrosin A inhibited chitin synthase II by 50% at the concentration of 104 μg/ml in an enzyme assay system. This compound showed antifungal activities against Rhizoctonia solani, Pyricularia oryzae, Botrytis cinerea. Cryptococcus neoformans and Trichophyton mentagrophytes.

Phellinsin A, a novel chitin synthases inhibitor was isolated from the cultured broth of fungus PL3, which was identified as Phellinus sp. PL3. Phellinsin A was purified by solvent partition, silica gel, ODS column chromatographies, and preparative HPLC, consecutively. The structure of phellinsin A was assigned as a phenolic compound on the basis of various spectroscopic analyses including UV, IR, Mass, and NMR. Its molecular weight and formula were found to be 358 and C18H14O8, respectively. Phellinsin A selectively inhibited chitin synthase I and II of Saccharomyces cerevisiae with an IC50 value of 76 and 28 microg/ml, respectively, in our cell free assay system. This compound showed antifungal activity against Colletotrichum lagenarium, Pyricularia oryzae, Rhizoctonia solani, Aspergillus fumigatus, and Trichophyton mentagrophytes.

Two new peptides, tylopeptins A and B, were isolated from the methanol extract of the fruiting body of the mushroom, Tylopilus neofelleus. These peptides were identified as peptaibols possessing an acetylated N-terminal residue, fourteen amino acids, and leucinol as the C-terminal amino alcohol. Sequential determination and complete 1H and 13C resonance assignments were based on positive ion FAB mass spectroscopy and two dimensional NMR techniques. These peptides were subsequently shown to be active against some gram-positive bacteria, but inactive against pathogenic fungi and gram-negative bacteria.

A new free radical scavenger named inoscavin E was isolated from the fruiting bodies of Inonotus xeranticus. Its structure was determined as 2-(3,4-dihydroxyphenyl)-6-[(1E)-2-(3,4-dihydroxyphenyl)ethenyl]-4H-furo[3,2-c]pyran-4-one on the basis of spectroscopic analysis. Inoscavin E exhibited significant scavenging activity against the superoxide radical anion and ABTS radical cation.

Geninthiocin was isolated from the mycelium of Streptomyces sp. DD84 as a tip A promoter inducing substance. Based on various NMR studies, its structure was established as a thiopeptide with oxazole and thiazole moieties, and several unusual amino acids.

Two new antioxidants, phellinin B, a mixture of (I) and (IIa), and C (IIb), are isolated from the culture broth of the title wood fungus.

Xylarinols A and B, two new 2-benzoxepin derivatives from the fruiting bodies of Xylaria polymorpha

Two new polypropionates designated as xylarinic acids A and B were isolated from the fruiting body of Xylaria polymorpha. Their structures were established as 4,6,8-trimethyl-2,4-decadienoic acid and 2,4,6-trimethyl-2-octenoic acid, respectively, on the basis of extensive spectroscopic analysis. Both compounds displayed significant antifungal activity against plant pathogenic fungi Pythium ultinum, Magnaporthe grisea, Aspergillus niger, Alternaria panax, and Fusarium oxysporium, whereas they did not show antibacterial and cytotoxic effect.

New melanin synthesis inhibitors, melanocins A, B and C, were isolated from the fermentation broth and extract of mycelium of Eupenicillium shearii F80695. The structures of melanocins were established by spectroscopic methods. They are formamide compounds. In particular, melanocin A has an isocyanide group.

A diketopiperazine (1) has been isolated from the culture broth of Penicillium sp. F70614 and its structure has been determined to be cyclo(dehydroala-L-Leu) by various spectroscopic analyses. This compound selectively inhibited yeast alpha-glucosidase and porcine intestinal alpha-glucosidase with IC50 values of 35 and 50 microg/ml, respectively. However, it did not show significant inhibitory effects against almond beta3-glucosidase, Aspergillus alpha-galactosidase, Escherichia coli beta-galactosidase and jack bean alpha-mannosidase.

Phenazostatins A and B, new diphenazine compounds, were isolated from the culture broth of Streptomyces sp. 833 as new neuronal cell protecting substances which also showed free radical scavenging activity. In the cell assay, phenazostatins A and B inhibited glutamate toxicity in N18-RE-105 cells with EC50 values of 0.34 and 0.33 microM, respectively.

9-Hydroxycrisamicin A, a new cytotoxic isochromanquinone antibiotic, was isolated from a soil microorganism SA246 which was identified as Micromonospora sp. The molecular formula of 9-hydroxycrisamicin A was determined as C32H22O13 based on the HRFAB-MS analysis, and the structure was determined by various NMR experiments. 9-Hydroxycrisamicin A showed weak antimicrobial activity against Gram-positive bacteria and strong cytotoxic activity against some human cancer cell lines such as SK-OV-3 (ovarian), HCT15 (colon), SK-MEL-2 (melanoma), A549 (lung), XF498 (central nervous system) with ED50 of 0.47-0.65 microgram/ml.

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases which include collagenases, stromelysins and gelatinases1^ In the MMPfamily, gelatinase A (72-kDa type IV collagenase, EC 3.4.24.24) is unique in its ability to cleave type IV collagen, a principle structural component of basement membrane. This enzyme has thus been implicated in tumor cell invasion and metastasis, as well as angiogenesis and other connective tissue diseases2). Consequently gelatinase inhibitors may be of value in the therapy ofcancers as well as other disease states involving tissue remodeling. Matlystatins3) and BE16627B4) have been isolated from Actinomadura altramentaria and Streptomyces sp., respectively, as gelatinase inhibitors.