Structure and Biological Activity of 8-Deoxyheronamide C from a Marine-Derived Streptomyces sp.: Heronamides Target Saturated Hydrocarbon Chains in Lipid Membranes

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• 作者：Ryosuke Sugiyama ; Shinichi Nishimura ; Nobuaki Matsumori ; Yuta Tsunematsu ; Akira Hattori ; Hideaki Kakeya
• 刊名：Journal of the American Chemical Society
• 出版年：2014
• 出版时间：April 9, 2014
• 年：2014
• 卷：136
• 期：14
• 页码：5209-5212
• 全文大小：267K
• 年卷期：v.136,no.14(April 9, 2014)
• ISSN：1520-5126

文摘

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.