YO-001A

Structure
NPEdia
Producing organism
Streptomyces sp. YO15-A001
Biological activity
antifungal, inhibition of the FOF1-ATPase activity
Abstract
A new antifungal compound YO-001A was found from the culture broth of Streptomyces sp. YO15-A001, which was isolated from a soil sample collected in Toyama Prefecture. YO-001A was identified through morphological changes-based screening of the rice blast fungus, Pyricularia oryzae (P. oryzae). YO-001A is a new 26-membered macrolide of the oligomycin family, which exhibits potent antifungal activity against P. oryzae with an IC50 of 0.012 µM by disrupting mitochondrial respiration via inhibition of the FOF1-ATPase activity.
References
  • Yamamoto K, Futamura Y, Uson-Lopez RA, Aono H, Shimizu T, Osada H.: YO-001A, a new antifungal agent produced by Streptomyces sp. YO15-A001.
    J Antibiot, 72, 986-990 (2019) PMID:31601980 [ doi: 10.1038/s41429-019-0239-z ]
  • Metarhizin C

    Structure
    NPEdia
    Producing organism
    Tolypocladium album sp. RK17-F0007
    Biological activity
    selective cytotoxicity against osteosarcoma MG-63
    Abstract
    Metarhizin C, a stereoisomer of BR-050 was isolated from a fungus Tolypocladium album RK17-F0007 through a screening program to search for new antitumor compounds. A structure of the isomer was determined by spectroscopic methods including detailed analysis of NOESY correlation and mass spectrometry, and found to be identical to that of 3-desacylmetarhizin A with the absolute structure. Previously, it had been isolated by Kikuchi et al and proposed as BR-050 including the stereo-structure. However, detailed analysis for the newly isolated isomer confirmed that 3-desacylmetarhizin A was not identical to BR-050. Therefore, we assigned it metarhizin C as a new BR-050 isomer. Metarhizin C showed selective cytotoxicity against osteosarcoma MG-63 cells in a glucose independent condition with IC50 value of 0.79 µg/ml, while > 30 µg/ml of IC50 value in a normal condition, and inhibited a mitochondrial respiration.
    References
  • Nogawa T, Kawatani M, Okano A, Futamura Y, Aono H, Shimizu T, Kato N, Kikuchi H, Osada H.: Structure and biological activity of Metarhizin C, a stereoisomer of BR-050 from Tolypocladium album RK17-F0007
    J Antibiot, 72, 996-1000 (2019) PMID:31395970 [ doi: 10.1038/s41429-019-0229-1 ]
  • Nocardamin glucuronide

    Structure
    NPEdia
    Producing organism
    Streptomyces sp. 80H647
    Biological activity
    siderophore
    Abstract
    A new siderophore glucuronide, nocardamin glucuronide, was isolated together with nocardamin by applying the one strain-many compounds (OSMAC) approach to the ascamycin-producing strain, Streptomyces sp. 80H647, and performing multivariate analysis using mass spectral data. Structure elucidation was accomplished by a combination of NMR and MS analyses. The absolute configuration of the glucuronic acid moiety was found to be β-D-GlcA by hydrolysis using β-glucuronidase, subsequent derivatization of the hydrolysate, and comparison with standards. The siderophore activity of nocardamin glucuronide was evaluated through the chrome azurol S assay and was comparable to that of nocardamin and deferoxamine (IC50 13.4, 9.5, and 6.3 μM, respectively). Nocardamin glucuronide is the first example of a siderophore glucuronide.
    References
  • Lopez JAV, Nogawa T, Futamura Y, Shimizu T, Osada H.: Nocardamin glucuronide, a new member of the ferrioxamine siderophores isolated from the ascamycin-producing strain Streptomyces sp. 80H647.
    J Antibiot, 72, 991-995 (2019) PMID:31395970 [ doi: 10.1038/s41429-019-0217-5 ]
  • Zearalenone and zearalenone cleavage product

    Structure
    Zearalenone: NPEdia
    Zearalenone
    Zearalenone cleavage product: NPEdia
    Zearalenone cleavage product
    Producing organism
    Fusarium (zearalenone),
    Clonostachys roseal
    IFO 7063 (cleavage product)
    Biological activity
    estrogenic activity (zearalenone),
    detoxified compound (cleavage product)
    Abstract
    Zearalenones are mycotoxins with estrogenic activity consisting of a resorcinol moiety fused to a 14-membered macrocyclic lactone and are produced by various Fusarium species. We found that Clonostachys rosea IFO 7063 was effectively capable of converting zearalenone to cleavage product, 1-(3,5-dihydroxyphenyl)-10′-hydroxy-1′E-undecene-6′-one. Moreover, the cleavage product did not show potent estrogenic activity like that of Zearalenone and 17β-estradiol in the human breast cancer MCF-7 cell proliferation assay.
    References
  • Takahashi-Ando N, Kimura M, Kakeya H, Osada H, Yamaguchi I.: A novel lactonohydrolase responsible for the detoxification of zearalenone: enzyme purification and gene cloning.
    Biochem J, 365(Pt 1), 1-6 (2002) PMID: 11978180 [ doi: 10.1042/BJ20020450 ]
  • Kakeya H, Takahashi-Ando N, Kimura M, Onose R, Yamaguchi I, Osada H.: Biotransformation of the mycotoxin, zearalenone, to a non-estrogenic compound by a fungal strain of Clonostachys sp.
    Biosci Biotechnol Biochem, 66(12), 2723-2726 (2002) PMID: 12596876 [ doi: 10.1271/bbb.66.2723 ]
  • Kinanthraquinone

    Structure
    NPEdia
    Producing organism
    Streptomyces reveromyceticus SN-593-44
    Biological activity
    cytotoxocity
    Abstract
    A new anthraquinone derivative, kinanthraquinone was isolated from Streptomyces reveromyceticus SN-593-44. Its structure was determined by the combination of spectroscopic methods including NMR and MS. Kinanthraquinone had a characteristic carboxamide group and was a rare class of metabolite as an anthraquinone derivative isolated from microbes. It showed moderate cytotoxocity against HL-60 and srcts-NRK cell with IC50 value of 7.9 and 10 μM, respectively.
    References
  • Takagi H, Nogawa T, Futamura Y, Takahashi S, Osada H.: Kinanthraquinone, a new anthraquinone carboxamide isolated from Streptomyces reveromyceticus SN-593-44.
    J Antibiot, 71, 480-482 (2018) PMID: 29410517 [ doi: 10.1038/s41429-017-0020-0 ]
  • Hitoyopodin A, 15-Hydroxy hitoyopodin A, 13-Hydroxy hitoyopodin A

    Structure
    Hitoyopodin A (1): NPEdia
    Hitoyopodins

    15-Hydroxy hitoyopodin A (2): NPEdia
    15-Hydroxy hitoyopodin A

    13-Hydroxy hitoyopodin A (3): NPEdia
    13-Hydroxy hitoyopodin A (3)

    Producing organism
    Coprinopsis cinerea (NBRC 100011)
    Biological activity
    Growth Inhibition
    • Hitoyopodin A (1): HL-60 cells (IC50 = 3.7 μM), Plasmodium falciparum (IC50 = 6.7 μM)
    • 15-Hitoyopodin A (2): HL-60 cells (IC50 = 16 μM),
    • 13-Hitoyopodin A (3): HL-60 cells (IC50 = 14 μM), Plasmodium falciparum (IC50 = 25 μM)
    Abstract
    Three sesquiterpenoids, hitoyopodin A (1) and its hydroxy derivatives 2 and 3, were isolated from the culture broth of the mushroom Coprinopsis cinerea. Their absolute structures (1–3) with a benzoxabicyclo[3.2.1]octane core were determined by spectroscopy, X-ray crystallography, and total synthesis of 1. Compound 1 displays antiproliferative activity against HL-60 cancer cells and the malarial parasite Plasmodium falciparum.
    Reference
  • Otaka J, Shimizu T, Futamura Y, Hashizume D, Osada H.: Structures and synthesis of hitoyopodins: bioactive aromatic sesquiterpenoids produced by the mushroom Coprinopsis cinerea.
    Org Lett, [Epub ahead of print] (2018) PMID: 30234313 [ doi: 10.1021/acs.orglett.8b02788 ]
  • Wakodecaline A, B

    Structure
    A: NPEdia
    Wakodecaline A
    B: NPEdia
    Wakodecaline B
    Producing organism
    Pyrenochaetopsis sp. RK10-F058
    Biological activity
    moderate antimalarial activity
    Abstract
    Two new decaline metabolites, wakodecalines A and B, were isolated from a fungus, Pyrenochaetopsis sp. RK10-F058, by screening for structurally unique metabolites using LC/MS analysis. Their structures were determined on the basis of NMR and mass spectrometric measurements. The absolute structures were confirmed by a combination of chemical methods including chemical degradation, a modified Mosher’s method and Marfey’s method, and comparison of the experimental electronic CD (ECD) spectrum with calculated one. Both compounds had a cyclopentanone-fused decaline skeleton and an N-methylated amino acid moiety derived from a serine. They showed moderate antimalarial activity against the Plasmodium falciparum 3D7 strain.
    References
  • Nogawa T, Kato N, Shimizu T, Okano A, Futamura Y, Takahashi S, Osada H.: Wakodecalines A and B, new decaline metabolites isolated from a fungus Pyrenochaetopsis sp. RK10-F058.
    J Antibiot, 71, 123–128 (2018) PMID: 28901329 [ doi: 10.1038/ja.2017.103 ]
  • Polyoxin A, B, C, D, E, F, G, H, I, J, K, L, M

    Structure

    Polyoxin
    PolyoxinR1R2R3
    A CH2OH NPEdia
    B OH CH2OH NPEdia
    C OH H CH2OH NPEdia
    D OH Carboxy NPEdia
    E OH Carboxy NPEdia
    F Carboxy NPEdia
    G OH NPEdia
    H Me NPEdia
    I H NPEdia
    J OH Me NPEdia
    K H NPEdia
    L OH H NPEdia
    M OH H NPEdia
    Producing organism
    Streptomyces cacaoi var. asoensis
    Biological activity
    fungal cell wall synthesis inhibition
    Abstract
    Polyoxin A-M were found to be a new class of peptide nucleosides. Hydrolytic degradation of polyoxins afforded three groups of unusual α-L-amino acids, i.e., 1-(5'-amino-5'-deoxy-β-D-allofuranuronosyl)-5-hydroxymethyluracil (polyoxin C) or its three nucleobase analogs, 5-O-carbamoyl-2-amino-2-deoxy-L-xylonic acid or its 3-deoxy analog, and 3-ethylidene-L-azetidine-2-carboxylic acid. These structures were established on chemical and spectoroscopic evidence. 5'-Aminofuranuronoside common to all polyoxins constitutes a nucleoside with α-amino acid nature. Sequence analysis showed polyoxins are di- or tripeptide of these moieties. The structures so elucidated embody all the interesting chemical features of polyoxins.
    References
    isolation and structural determination
  • Isono K, Asahi K, Suzuki S.: Studies on polyoxins, antifungal antibiotics. 13. The structure of polyoxins.
    J Am Chem Soc, 91(26): 7490-7505 (1969) PMID: 5358618
  • Shibuya K, Tanaka M, Nanbata T, Isono K, Suzuki S.: Transformation of Polyoxins D, E, and F with Sodium Bisulfite.
    Agric Biol Chem, 36(7): 1229-1236 (1972) [ doi: 10.1271/bbb1961.36.1229 ]
  • Isono K and Suzuki S.: The Polyoxins: Pyrimidine Nucleoside Peptide Antibiotics Inhibiting Fungal Cell Wall Biosynthesis.
    Heterocycles, 13(1): 333-351(1979) [ doi: 10.3987/S-1979-01-0333 ]
  • Hanessian S, Fu JM, Tu Y, Isono K.: Structural identity and stereochemical revision of polyoximic acid.
    Tetrahedron Lett, 34(26): 4153-4156 (1993) [ doi: 10.1016/S0040-4039(00)60515-4 ]
  • Hitoyol A, B

    Structure
    A: NPEdia
    B: NPEdia
    Hitoyol A Hitoyol B
    A B
    Producing organism
    Coprinopsis cinerea (NBRC 100011)
    Biological activity
    hitoyol A, no activities
    hitoyol B, weak anti-malarial activity
    Abstract
    Hitoyol A and B, isolated from the culture broth of Basidiomycete Coprinopsis cinerea (NBRC 100011), are novel skeletal norsesquiterpenoids. Their structures and absolute configurations were determined by the extensive spectroscopic analyses including X-ray and ECD. Hitoyol A was possibly biosynthesized from a known sesquiterpenoid lagopodin B via a decarboxylation-induced cyclization. Hitoyol B showed weak anti-malarial activity (IC50 = 59 μM).
    References
    Isolation, identification, and biological activities
  • Otaka J, Hashizume D, Masumoto Y, Muranaka A, Uchiyama M, Koshino H, Futamura Y, Osada H.: Hitoyol A and B, Two Norsesquiterpenoids from the Basidiomycete Coprinopsis cinerea.
    Org Lett, 19(15), 4030–4033 (2017) PMID: 28726419 [ doi: 10.1021/acs.orglett.7b01784 ]
  • Opantimycin A

    Structure
    NPEdia
    Producing organism
    Streptomyces sp. RK88-1355
    Biological activity
    cytotoxicity and antimalarial activity
    Abstract
    A new metabolite containing a γ-butyrolactone and 2-hydroxy-3- formylaminobenzoic acid moieties, opantimycin A was isolated from a microbial metabolite fraction library generated from Streptomyces sp. RK88-1355 by search of an LC/MS-based spectral database named NPPlot: Natural Products Plot. The structure was determined based on extensive spectroscopic methods including NMR, MS and MS/MS experiments. It showed moderate cytotoxicity against HL-60 cell lines and antimalarial activity against Plasmodium falciparum 3D7.
    References
    isolation and structural determination
  • Nogawa T, Okano A, Lim CL, Futamura Y, Shimizu T, Takahashi S, Ibrahim D, Osada H.: Opantimycin A, a new metabolite isolated from Streptomyces sp. RK88-1355.
    J Antibiot, 70(2): 222-225 (2017) PMID: 27599762 [ doi: 10.1038/ja.2016.113 ]
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