title: Biosynthesis of nectrisine in Thelonectria discophora SANK 18292.
abstract: Nectrisine, an iminosugar with a heterocyclic nitrogen-containing 5-membered ring, acts as a glycosidase inhibitor. Thelonectria discophora SANK 18292, a fungus, was identified as a nectrisine producer from its microbial library in our screening for nectrisine producing microorganisms. Biosynthesis of nectrisine produced by the fungus was studied using stable isotope tracer techniques. Incorporation of (13)C-labeled d-ribose and d-xylose into nectrisine was confirmed by mass spectrometry and (13)C NMR spectroscopy, which suggested that these were its precursors. Chromatographic separation of the hot water extract from the culture broth afforded not only nectrisine, but also substantial amounts of 4-amino-4-deoxyarabinitol. Incubation of the latter with the crude enzyme of the fungus at room temp. caused an increase in levels of nectrisine together with a decrease in amounts of the administered potential precursor suggesting that it is a biosynthetic intermediate. From these results, a biosynthetic pathway to nectrisine is proposed via d-xylulose 5-phosphate and 4-amino-4-deoxyarabinitol by the pentose phosphate pathway.
authors: New Modality Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. Electronic address: miyauchi.ryuki.d4@daiichisankyo.co.jp.
authors: Ryuki
authors: R
authors: Miyauchi
authors: Center for Pharmaceutical and Biomedical Analysis, Daiichi Sankyo RD Novare Co., Ltd., 1-16-13, Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan.
authors: Toshio
authors: T
authors: Takatsu
authors: Analytical and Quality Evaluation Research Laboratories, Pharmaceutical Technology Division, Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
authors: Tetsuya
authors: T
authors: Suzuki
authors: Discovery Science and Technology Department, Drug Discovery and Biomedical Technology Unit, Daiichi Sankyo RD Novare Co., Ltd., 1-16-13, Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan.
authors: Yasunori
authors: Y
authors: Ono
authors: CM&C Planning Department, Pharmaceutical Technology Division, Daiichi Sankyo Co., Ltd., 1-12-1, Shinomiya, Hiratsuka-shi, Kanagawa 254-0014, Japan.
authors: Yoichiro
authors: Y
authors: Shiba
mesh_terms: D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors; D006999:Hypocreales / Q000737:chemistry*; D050113:Imino Furanoses / Q000737:chemistry / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010428:Pentosephosphates / Q000737:chemistry; D012266:Ribose / Q000737:chemistry; D013237:Stereoisomerism; D013402:Sugar Alcohols / Q000737:chemistry / Q000378:metabolism; D014326:Tropanes / Q000737:chemistry / Q000378:metabolism; D014994:Xylose / Q000737:chemistry
chemical_list: C000604270:3-tigloyloxy-6,7-epoxytropane; C000604269:4-amino-4-deoxyarabinitol; D050113:Imino Furanoses; D010428:Pentosephosphates; D013402:Sugar Alcohols; D014326:Tropanes; C055825:nectrisine; C031625:xylulose-5-phosphate; D012266:Ribose; D014994:Xylose; D006026:Glycoside Hydrolases
keywords: Aminoalcohol; Biosynthesis; Iminosugar; Nectriaceae; Nectrisine; Thelonectria discophora