title: Structure and biological activity of 8-deoxyheronamide C from a marine-derived Streptomyces sp.: heronamides target saturated hydrocarbon chains in lipid membranes.
abstract: Polyene macrolactams are a class of microbial metabolites, many of which show potent biological activities with unidentified modes of action. Here we report that 8-deoxyheronamide C, a new 20-membered polyene macrolactam from a marine-derived actinomycete Streptomyces sp., is a unique membrane binder. 8-Deoxyheronamide C showed a characteristic sensitivity profile against fission yeast sterol mutant cells, indicating that the metabolite targets cell membranes. We detected tight physical interaction between heronamides including 8-deoxyheronamide C and heronamide C and saturated hydrocarbon chains in lipid membranes using surface plasmon resonance experiments. We further show that heronamides induced abnormal cell wall morphology in fission yeast probably by perturbing the structure of membrane microdomains. This work will accelerate the biological and medical investigation of polyene macrolactams.
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.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Sugiyama
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nishimura
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Matsumori
authors.forename: Yuta
authors.initials: Y
authors.lastname: Tsunematsu
authors.forename: Akira
authors.initials: A
authors.lastname: Hattori
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kakeya
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006838:Hydrocarbons / Q000737:chemistry / Q000378:metabolism*; D047029:Lactams, Macrocyclic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008563:Membrane Lipids / Q000737:chemistry* / Q000378:metabolism; D008968:Molecular Conformation; D015394:Molecular Structure; D012568:Schizosaccharomyces / Q000166:cytology / Q000187:drug effects*; D013302:Streptomyces / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D006838:Hydrocarbons; D047029:Lactams, Macrocyclic; D008563:Membrane Lipids; C555720:heronamide C