The University of Tokyo · Biochemistry, Genetics and Molecular Biology
Professor Shinichi Nishimura's research lab specializes in natural product chemistry, with a focus on the isolation, structural elucidation, and biological evaluation of bioactive compounds from marine organisms and fungi. The lab investigates enzyme inhibitors—particularly geranylgeranyltransferase I inhibitors—derived from sponges, as well as membrane-targeting natural products that interact with lipid membranes and sterols. A key direction involves developing fluorescent probes for cholesterol imaging and exploring the molecular mechanisms of natural products in cellular membranes. The lab also engages in the discovery of novel metabolites through innovative analytical techniques such as mass spectrometry-based molecular networking and total synthesis to confirm structures and bioactivities.
Figures are computed from collected data and may differ slightly.
Massadine, a highly oxygenated alkaloid, was isolated from the marine sponge Stylissa aff. massa as an inhibitor of geranylgeranyltransferase type I (GGTase I). The structure of massadine has been deduced from spectral data. Massidine inhibited GGTase I from Candida albicans with an IC(50) value of 3.9 microM. [structure: see text]
Covering: up to 2019Nature furnishes bioactive compounds (natural products) with complex chemical structures, yet with simple, sophisticated molecular mechanisms. When natural products exhibit their activities in cells or bodies, they first have to bind or react with a target molecule in/on the cell. The cell membrane is a major target for bioactive compounds. Recently, our understanding of the molecular mechanism of interactions between natural products and membrane lipids progressed with the a
Two new polyacetylenic acids, corticatic acids D (2) and E (3), have been isolated from the marine sponge Petrosia corticata along with the known corticatic acid A (1) as geranylgeranyltransferase type I (GGTase I) inhibitors. Their structures were elucidated on the basis of spectroscopic and chemical methods. Compounds 1-3 inhibited GGTase I from Candida albicans with IC(50) values of 1.9-7.3 microM.
Cholesterol plays important roles in biological membranes. The cellular location where cholesterol molecules work is prerequisite information for understanding their dynamic action. Bioimaging probes for cholesterol molecules would be the most powerful means for unraveling the complex nature of lipid membranes. However, only a limited number of chemical or protein probes have been developed so far for cytological analysis. Here we show that fluorescently-labeled derivatives of theonellamides act
Ferrichromes are a family of fungal siderophores with cyclic hexapeptide structures. Most fungi produce one or two ferrichrome-type siderophores. <i>Acremonium persicinum</i> MF-347833 produces ferrichrome-like potent Trojan horse antifungal antibiotics ASP2397 and AS2488053, the aluminum- and iron-chelating forms of AS2488059, respectively. Here, we show by gene sequencing followed by gene deletion experiments that <i>A. persicinum</i> MF-347833 possesses two nonribosomal peptide synthetase gen
Abstract A series of lipidic spirohemiaminals, designated streptoaminals, is reported. These were discovered by surveying the unique molecular signatures identified in the mass spectrometry data of the combined‐culture broth of Streptomyces nigrescens HEK616 and Tsukamurella pulmonis TP‐B0596. Mass spectrometry analysis showed that streptoaminals appeared as a cluster of ion peaks, which were separated by 14 mass unit intervals, implying the presence of alkyl chains of different lengths. The che
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