Metarhizin C

Structure

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) [ doi: 10.1038/s41429-019-0229-1 ]

Nocardamin glucuronide

Structure

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) [ doi: 10.1038/s41429-019-0217-5 ]

Zearalenone and zearalenone cleavage product

Structure

Zearalenone:

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) [ 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) [ doi: 10.1271/bbb.66.2723 ]

Kinanthraquinone

Structure

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) [ doi: 10.1038/s41429-017-0020-0 ]

Hitoyopodin A, 15-Hydroxy hitoyopodin A, 13-Hydroxy hitoyopodin A

Structure

Hitoyopodin A (1):

15-Hydroxy hitoyopodin A (2):

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) [ doi: 10.1021/acs.orglett.8b02788 ]

Wakodecaline A, B

Structure

A:

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) [ doi: 10.1038/ja.2017.103 ]

Structure

Polyoxin	R1	R2	R3
A
B
C
D
E
F
G
H
I
J
K
L
M

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)

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:
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) [ doi: 10.1021/acs.orglett.7b01784 ]

Opantimycin A

Structure

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) [ doi: 10.1038/ja.2016.113 ]