Dataset Information

Creation of an HDAC-based yeast screening method for evaluation of marine-derived actinomycetes: discovery of streptosetin A.

ABSTRACT: A histone deacetylase (HDAC)-based yeast assay employing a URA3 reporter gene was applied as a primary screen to evaluate a marine-derived actinomycete extract library and identify human class III HDAC (SIRT) inhibitors. On the basis of the bioassay-guided purification, a new compound designated as streptosetin A (1) was obtained from one of the active strains identified through the yeast assay. The gross structure of the new compound was elucidated from the 1D and 2D NMR data. The absolute stereostructure of 1 was determined based on X-ray crystal structure analysis and simulation of ECD spectra using time-dependent density functional theory calculations. This compound showed weak inhibitory activity against yeast Sir2p and human SIRT1 and SIRT2.

SUBMITTER: Amagata T

PROVIDER: S-EPMC3532527 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Creation of an HDAC-based yeast screening method for evaluation of marine-derived actinomycetes: discovery of streptosetin A.

Amagata Taro T Xiao Jing J Chen Yi-Pei YP Holsopple Nicholas N Oliver Allen G AG Gokey Trevor T Guliaev Anton B AB Minoura Katsuhiko K

Journal of natural products 20121120 12

A histone deacetylase (HDAC)-based yeast assay employing a URA3 reporter gene was applied as a primary screen to evaluate a marine-derived actinomycete extract library and identify human class III HDAC (SIRT) inhibitors. On the basis of the bioassay-guided purification, a new compound designated as streptosetin A (1) was obtained from one of the active strains identified through the yeast assay. The gross structure of the new compound was elucidated from the 1D and 2D NMR data. The absolute ster ...[more]

PMID: 23167691

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Project description:Plastics are present in the majority of daily-use products worldwide. Due to society's production and consumption patterns, plastics are accumulating in the environment, causing global pollution issues and intergenerational impacts. Our work aims to contribute to the development of solutions and sustainable methods to mitigate this pressing problem, focusing on the ability of marine-derived actinomycetes to accelerate plastics biodegradation and produce polyhydroxyalkanoates (PHAs), which are biodegradable bioplastics. The thin plastic films' biodegradation was monitored by weight loss, changes in the surface chemical structure (Infra-Red spectroscopy FTIR-ATR), and by mechanical properties (tensile strength tests). Thirty-six marine-derived actinomycete strains were screened for their plastic biodegradability potential. Among these, Streptomyces gougerotti, Micromonospora matsumotoense, and Nocardiopsis prasina revealed ability to degrade plastic films-low-density polyethylene (LDPE), polystyrene (PS) and polylactic acid (PLA) in varying conditions, namely upon the addition of yeast extract to the culture media and the use of UV pre-treated thin plastic films. Enhanced biodegradation by these bacteria was observed in both cases. S. gougerotti degraded 0.56% of LDPE films treated with UV radiation and 0.67% of PS films when inoculated with yeast extract. Additionally, N. prasina degraded 1.27% of PLA films when these were treated with UV radiation, and yeast extract was added to the culture medium. The main and most frequent differences observed in FTIR-ATR spectra during biodegradation occurred at 1740 cm-1, indicating the formation of carbonyl groups and an increase in the intensity of the bands, which indicates oxidation. Young Modulus decreased by 30% on average. In addition, S. gougerotti and M. matsumotoense, besides biodegrading conventional plastics (LDPE and PS), were also able to use these as a carbon source to produce degradable PHA bioplastics in a circular economy concept.

Project description:Increasing attention has been paid to marine-derived biomolecules as sources of therapeutics for autoimmune diseases. Nagasaki Prefecture has many islands and is surrounded by seas, straits, gulfs, bays, and coves, giving it the second longest coastline in Japan after Hokkaido. We have collected more than 20,000 marine microbes and have been preparing an original marine microbial extract library, which contains small and mid-size biomolecules that may penetrate cell membranes and interfere with the intracellular protein-protein interaction involved in the development of autoinflammatory diseases such as familial Mediterranean fever. In addition, we have been developing an indoor shark farming system to prepare shark nanobodies that could be developed as potential therapeutic agents for autoimmune diseases. Sharks produce heavy-chain antibodies, called immunoglobulin new antigen receptors (IgNARs), consisting of one variable domain (VNAR) and five constant domains (CNAR); of these, VNAR can recognize a variety of foreign antigens. A VNAR single domain fragment, called a nanobody, can be expressed in Escherichia coli and has the properties of an ideal therapeutic candidate for autoimmune diseases. Shark nanobodies contain complementarity-determining regions that are formed through the somatic rearrangement of variable, diversity, and joining segments, with the segment end trimming and the N- and P-additions, as found in the variable domains of mammalian antibodies. The affinity and diversity of shark nanobodies are thus expected to be comparable to those of mammalian antibodies. In addition, shark nanobodies are physically robust and can be prepared inexpensively; as such, they may lead to the development of highly specific, stable, effective, and inexpensive biotherapeutics in the future. In this review, we first summarize the history of the development of conventional small molecule drugs and monoclonal antibody therapeutics for autoimmune diseases, and then introduce our drug discovery system at Nagasaki University, including the preparation of an original marine microbial extract library and the development of shark nanobodies.

Dataset Information

Creation of an HDAC-based yeast screening method for evaluation of marine-derived actinomycetes: discovery of streptosetin A.

Publications

Creation of an HDAC-based yeast screening method for evaluation of marine-derived actinomycetes: discovery of streptosetin A.

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