New Milbemycins from Streptomyces hygroscopicus subsp. aureolacrimosus. Fermentation, Isolation and Structure Elucidation.

Nonaka, Kazuhiro; Tsukiyama, Takahiro; Okamoio, Yoshihiro; Sato, Kazuo; Kumasaka, Chieko; Yamamoto, Takahiro; Maruyama, Fumio; Yoshikawa, Hiroji

doi:10.7164/antibiotics.53.694

Cited by 27 publications

(11 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FK506 was originally discovered as an antifungal, and as an inhibitor of CaCdr1p (19) it reverses multidrug efflux in C. albicans (34,53). The milbemycins are 16-membered ring macrolides belonging to families that are used as insecticides, acaricides, and anthelminthics (44,60). Some milbemycins have also been identified as chemosensitizers of fungal multidrug efflux mediated by CaCdr1p (33).…”

mentioning

confidence: 99%

Characterization of Three Classes of Membrane Proteins Involved in Fungal Azole Resistance by Functional Hyperexpression inSaccharomyces cerevisiae

et al. 2007

View full text Add to dashboard Cite

The study of eukaryotic membrane proteins has been hampered by a paucity of systems that achieve consistent high-level functional protein expression. We report the use of a modified membrane protein hyperexpression system to characterize three classes of fungal membrane proteins (ABC transporters Pdr5p, CaCdr1p, CaCdr2p, CgCdr1p, CgPdh1p, CkAbc1p, and CneMdr1p, the major facilitator superfamily transporter CaMdr1p, and the cytochrome P450 enzyme CaErg11p) that contribute to the drug resistance phenotypes of five pathogenic fungi and to express human P glycoprotein (HsAbcb1p). The hyperexpression system consists of a set of plasmids that direct the stable integration of a single copy of the expression cassette at the chromosomal PDR5 locus of a modified host Saccharomyces cerevisiae strain, AD⌬. Overexpression of heterologous proteins at levels of up to 29% of plasma membrane protein was achieved. Membrane proteins were expressed with or without green fluorescent protein (GFP), monomeric red fluorescent protein, His, FLAG/His, Cys, or His/Cys tags. Most GFP-tagged proteins tested were correctly trafficked within the cell, and His-tagged proteins could be affinity purified. Kinetic analysis of ABC transporters indicated that the apparent K m value and the V max value of ATPase activities were not significantly affected by the addition of His tags. The efflux properties of seven fungal drug pumps were characterized by their substrate specificities and their unique patterns of inhibition by eight xenobiotics that chemosensitized S. cerevisiae strains overexpressing ABC drug pumps to fluconazole. The modified hyperexpression system has wide application for the study of eukaryotic membrane proteins and could also be used in the pharmaceutical industry for drug screening.The resolution and exploitation of protein structure and function are among the greatest biological challenges in the postgenomic era. These challenges, and their potential dividends, are greatest for membrane proteins, which are notoriously difficult to functionally express and purify in the quantities and forms needed for drug discovery or for high-resolution X-ray crystallography (1, 16). About a quarter of the cellular proteome consists of membrane proteins (5), which often play vital physiological roles: from environmental sensing to energy transduction, from nutrient uptake to drug efflux, and from cellular proliferation to programmed cell death. Membrane proteins are involved in many prominent diseases, including cystic fibrosis (48), type 2 diabetes (49), heart disease (52), and the drug resistance of numerous cancers (57). Hence, they are the targets for many therapies and constitute up to 70% of the drug targets used in medicine today. Membrane proteins also play key roles in drug modification, detoxification, and resistance in a wide variety of prokaryotic and eukaryotic systems (7). A fundamental understanding of cell biology, cell physiology, and cell-drug interactions therefore requires a detailed analysis of membrane protein function. Fu...

show abstract

mentioning

confidence: 99%

Characterization of Three Classes of Membrane Proteins Involved in Fungal Azole Resistance by Functional Hyperexpression inSaccharomyces cerevisiae

et al. 2007

View full text Add to dashboard Cite

show abstract

“…The LC 50 s of tested compounds were calculated using the probit method. Table 1 and revealed compound 1 possessed the same macrocyclic lactone skeleton as 5-oxomilbemycin A3 (milbemycin J) [7][8][9] and milbemycin β 12 [10]. Differences between compound 1 and 5-oxomilbemycin A3 were that the furan ring was missing and instead a C-27 aldehyde group was present in 1.…”

Section: Nematicidal Activity Testmentioning

confidence: 99%

New 5-oxomilbemycins from a Genetically Engineered Strain Streptomyces bingchenggensis BCJ60

Li¹,

Zhang²,

Zhang³

et al. 2017

Rec.Nat.Prod.

View full text Add to dashboard Cite

Abstract:Two new 5-oxomilbemycins, 27-aldehyde-5-oxomilbemycin β 12 (1) and 2-hydroxymilbemycin K (2), were isolated from a genetically engineered strain Streptomyces bingchenggensis BCJ60. Their structures were determined by comprehensive analyses of its 1 H and 13 C NMR, COSY, HMQC, and HMBC spectroscopic, HR-ESI-MS mass spectrometric and comparison with data from the literature. Preliminary studies showed that 27-aldehyde-5-oxomilbemycin β 12 (1) and 2-hydroxymilbemycin K (2) possessed strong acaricidal and nematocidal activities.

show abstract

“…Streptomyces avermectin, milbemycin, bafilomycin, leucanicidins, geldanamycin, fungichromin B, fervenulin, 3-methoxy-2-methyl-carbazole-1,4-quinone, carbazomycins D F, 3-benzyl-1,4-diaza-2, 5-dioxobicyclo[4.3.0] nonane (Burg , 1979;Lacey , 1995;Nonaka , 2000;Ruanpanun , 2010;Ruanpanun , 2011;Skantar , 2005;Yoon , 2012;Zeng , 2013 (Hesseltine , 1954) 5 100 ml GSS (1% soluble starch, 0.025% K 2 HPO 4 , 2.5% soybean meal, 0.1% beef extract, 0.4% yeast extract, 0.2% NaCl 2 g/l, 2% glucose, 0.2% CaCO 3 (pH7.2)) (Kim , 1989) 500 (polymerase chain reaction, PCR) (Lane, 1991).…”

Section: Incognitamentioning

confidence: 99%

Characterization of Streptomyces netropsis Showing a Nematicidal Activity against Meloidogyne incognita

Jang¹,

Choi²,

Joo³

et al. 2015

Research in Plant Disease

View full text Add to dashboard Cite

Control of nematode has become difficult owing to the restricted use of effective soil fumigant, methyl bromide, and other non-fumigant nematicides. Therefore, it is urgently necessary to develop microbial nematicide to replace chemical nematicides. In this study, the 50% aqueous methanol extraction solution of fermentation broths of 2,700 actinomycete strains were tested for their nematicidal activity against second stage of juveniles (J2s) of Meloidogyne incognita. As the results, only the 50% aqueous methanol extraction solution of AN110065, at 20% equivalent to 10% fermentation broth, showed strong nematicidal activity with 78.9% of mortality 24 h after treatment and 94.1% of mortality at 72 h. The 16S rRNA gene sequencing showed that the strain sequence was 99.78% identical to Streptomyces netropsis. The extract of S. netropsis AN110065 fermentation broth was successively partitioned with ethyl acetate and butanol and then the ethyl acetate, butanol and water layers were investigated for their nematicidal activity against the M. incognita. At 1,000 mg/ml, ethyl acetate layer showed the strongest activity of 83.5% of juvenile mortality 72 h after treatment. The pot experiment using the fermentation broth of AN110065 on tomato plant against M. incognita displayed that it evidently suppressed gall formation at a 10-fold diluent treatment. The tomato plants treated with the fermentation broth of S. netropsis AN110065 did not show any phytotoxicity. The results suggest that S. netropsis AN110065 has a potential to serve as microbial nematicide in organic agriculture.

show abstract

New Milbemycins from Streptomyces hygroscopicus subsp. aureolacrimosus. Fermentation, Isolation and Structure Elucidation.

Cited by 27 publications

References 7 publications

Characterization of Three Classes of Membrane Proteins Involved in Fungal Azole Resistance by Functional Hyperexpression inSaccharomyces cerevisiae

Characterization of Three Classes of Membrane Proteins Involved in Fungal Azole Resistance by Functional Hyperexpression inSaccharomyces cerevisiae

New 5-oxomilbemycins from a Genetically Engineered Strain Streptomyces bingchenggensis BCJ60

Characterization of Streptomyces netropsis Showing a Nematicidal Activity against Meloidogyne incognita

Contact Info

Product

Resources

About