title: Identification and characterization of natural microbial products that alter the free d-aspartate content of mammalian cells.
abstract: Mammalian cells possess the molecular apparatus necessary to take up, degrade, synthesize, and release free d-aspartate, which plays an important role in physiological functions within the body. Here, biologically active microbial compounds and pre-existing drugs were screened for their ability to alter the intracellular d-aspartate level in mammalian cells, and several candidate compounds were identified. Detailed analytical studies suggested that two of these compounds, mithramycin A and geldanamycin, suppress the biosynthesis of d-aspartate in cells. Further studies suggested that these compounds act at distinct sites within the cell. These compounds may advance our current understanding of biosynthesis of d-aspartate in mammals, a whole picture of which remains to be disclosed.
authors.affiliation: Laboratory of Biomolecular Science, Graduate School of Pharmaceutical and Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Katane
authors.affiliation: Laboratory of Biomolecular Science, Graduate School of Pharmaceutical and Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Yuusuke
authors.initials: Y
authors.lastname: Kaneko
authors.affiliation: Laboratory of Biomolecular Science, Graduate School of Pharmaceutical and Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Misaki
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Laboratory of Biomolecular Science, Graduate School of Pharmaceutical and Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Doi
authors.affiliation: Laboratory of Biomolecular Science, Graduate School of Pharmaceutical and Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Laboratory of Biomolecular Science, Graduate School of Pharmaceutical and Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Yukino
authors.initials: Y
authors.lastname: Kasuga
authors.affiliation: Laboratory of Biomolecular Science, Graduate School of Pharmaceutical and Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Yoshida
authors.affiliation: Laboratory of Biomolecular Science, Graduate School of Pharmaceutical and Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Saeka
authors.initials: S
authors.lastname: Kumakubo
authors.affiliation: Laboratory of Biomolecular Science, Graduate School of Pharmaceutical and Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Laboratory of Biomolecular Science, Graduate School of Pharmaceutical and Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Satsuki
authors.initials: S
authors.lastname: Matsuda
authors.affiliation: Laboratory of Biomolecular Science, Graduate School of Pharmaceutical and Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Takemitsu
authors.initials: T
authors.lastname: Furuchi
authors.affiliation: Laboratory of Biomolecular Science, Graduate School of Pharmaceutical and Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Saitoh
authors.affiliation: Laboratory of Biomolecular Science, Graduate School of Pharmaceutical and Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Masae
authors.initials: M
authors.lastname: Sekine
authors.affiliation: Laboratory of Microbial Chemistry, Graduate School of Pharmaceutical and Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Koyama
authors.affiliation: Laboratory of Microbial Chemistry, Graduate School of Pharmaceutical and Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tomoda
authors.affiliation: Laboratory of Biomolecular Science, Graduate School of Pharmaceutical and Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. Electronic address: hommah@pharm.kitasato-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Homma
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D016227:Benzoquinones / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology*; D016716:PC12 Cells; D008926:Plicamycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D012717:Sesquiterpenes / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D027322:Amino Acid Transport System X-AG; D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D012717:Sesquiterpenes; D001224:Aspartic Acid; C027285:heptelidic acid; C066851:mithramycin A; D008926:Plicamycin; C001277:geldanamycin
keywords: Geldanamycin; Mithramycin A; Natural products; d-Amino acid; d-Aspartate