title: Discovery and Total Synthesis of Streptoaminals: Antimicrobial [5,5]-Spirohemiaminals from the Combined-Culture of Streptomyces nigrescens and Tsukamurella pulmonis.
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 chemical structures of these compounds were elucidated by spectroscopic analysis and total synthesis. Streptoaminals with globular structures showed broad antimicrobial activities, whereas the planar structures of the 5-alkyl-1,2,3,4-tetrahydroquinolines found in the same combined-culture did not. This work shows the application of microbes as reservoirs for a range of chemical scaffolds.
authors.affiliation: Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.|Present address, RIKEN Center for Sustainable Resource Science, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Sugiyama
authors.affiliation: Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan. nshin@pharm.kyoto-u.ac.jp.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nishimura
authors.affiliation: Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, 113-8657, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Ozaki
authors.affiliation: Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, 113-8657, Japan.
authors.forename: Shumpei
authors.initials: S
authors.lastname: Asamizu
authors.affiliation: Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, 113-8657, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Onaka
authors.affiliation: Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan. scseigyo-hisyo@pharm.kyoto-u.ac.jp.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kakeya
mesh_terms: D000192:Actinomycetales / Q000166:cytology / Q000187:drug effects*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018929:Cell Culture Techniques; D055808:Drug Discovery; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013302:Streptomyces / Q000166:cytology / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D013141:Spiro Compounds
keywords: antimicrobial activity; combined-cultures; natural products; structure elucidation; total synthesis