Hyaluromycin, a new hyaluronidase inhibitor of polyketide origin from marine Streptomyces sp.
Hyaluromycin (1), a new member of the rubromycin family of antibiotics, was isolated from the culture extract of a marine-derived Streptomyces sp. as a HAase inhibitor on the basis of HAase activity screening. The structure of 1 was elucidated through the interpretation of NMR data for the compound and its 3″-O-methyl derivative in combination with an incorporation experiment with [1,2-13C2]acetate. The compound's absolute configuration was determined by the comparison of its circular dichroism (CD) spectrum with those of other rubromycins. Hyaluromycin (1) consists of a γ-rubromycin core structure possessing a 2-amino-3-hydroxycyclopent-2-enone (C5N) unit as an amide substituent of the carboxyl function; both structural units have been reported only from actinomycetes. Hyaluromycin (1) displayed approximately 25-fold more potent hyaluronidase inhibitory activity against hyaluronidase than did glycyrrhizin, a known inhibitor of plant origin.
Graduate School of Marine Science and Technology, Tokyo University of Marine Science and Technology, 4-5-7 Konan, Minato-ku, Tokyo 108-8477, Japan. enjuro.h@gmail.com.
Enjuro
E
Harunari
Graduate School of Marine Science and Technology, Tokyo University of Marine Science and Technology, 4-5-7 Konan, Minato-ku, Tokyo 108-8477, Japan. imada@kaiyodai.ac.jp.
Chiaki
C
Imada
Biotechnology Research Center, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan. yas@pu-toyama.ac.jp.
Yasuhiro
Y
Igarashi
Biotechnology Research Center, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan. z02113@st.pu-toyama.ac.jp.
Takao
T
Fukuda
Graduate School of Marine Science and Technology, Tokyo University of Marine Science and Technology, 4-5-7 Konan, Minato-ku, Tokyo 108-8477, Japan. terahara@kaiyodai.ac.jp.
Takeshi
T
Terahara
Graduate School of Marine Science and Technology, Tokyo University of Marine Science and Technology, 4-5-7 Konan, Minato-ku, Tokyo 108-8477, Japan. takeshik@kaiyodai.ac.jp.
Takeshi
T
Kobayashi
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002415:Cats; D002942:Circular Dichroism; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005285:Fermentation; D006575:Heterocyclic Compounds, 3-Ring / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006821:Hyaluronoglucosaminidase / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D008968:Molecular Conformation; D061065:Polyketides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011809:Quinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012623:Seawater / Q000382:microbiology; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013302:Streptomyces / Q000737:chemistry / Q000378:metabolism*; D014561:Urochordata / Q000382:microbiology*; D014871:Water Microbiology
D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D061065:Polyketides; D011809:Quinones; C000590755:hyaluromycin; D006821:Hyaluronoglucosaminidase