Terpenes from Marine-Derived Fungi

Terpenes from marine-derived fungi show a pronounced degree of structural diversity, and due to their interesting biological and pharmacological properties many of them have aroused interest from synthetic chemists and the pharmaceutical industry alike. The aim of this paper is to give an overview of the structural diversity of terpenes from marine-derived fungi, highlighting individual examples of chemical structures and placing them in a context of other terpenes of fungal origin. Wherever possible, information regarding the biological activity is presented

Epoxide-Opening Cascades in the Synthesis of Polycyclic Polyether Natural Products

The structural features of polycyclic polyether natural products can, in some cases, be traced to their biosynthetic origin. However in case that are less well understood, only biosynthetic pathways that feature dramatic, yet speculative, epoxide-opening cascades are proposed. We summarize how such epoxide-opening cascade reactions have been used in the synthesis of polycyclic polyethers (see scheme) and related natural products. The group of polycyclic polyether natural products is of special interest owing to the fascinating structure and biological effects displayed by its members. The latter includes potentially therapeutic antibiotic, antifungal, and anticancer properties, and extreme lethality. The polycyclic structural features of this class of compounds can, in some cases, be traced to their biosynthetic origin, but in others that are less well understood, only to proposed biosynthetic pathways that feature dramatic, yet speculative, epoxide-opening cascades. In this review we summarize how such epoxide-opening cascade reactions have been used in the synthesis of polycyclic polyethers and related natural products

管理栄養士を志す大学生の精神障害者に対する社会的態度の変容 : 専門知識を活かしたボランティア活動の効果

管理栄養士を志す大学生20名を対象に、精神障害者に対する社会的態度の変化を測定し、精神障害者理解を促す要因を抽出することを目的としてアンケート調査を実施した。方法は、精神障害者の就労支援としてキッチン業務(調理や盛り付け、配膳、食器洗浄など)を行っている施設で2日間のボランティア実習を行った。実習に先立ち質問紙(preアンケート)への回答を、さらに2日間の実習終了後に再度同じ質問紙(post アンケート)への回答を依頼し、得られた回答を数値化したうえで統計解析を行った。結果、精神障害者に対するイメージのなかで、生活面や人間関係の構築に関するいくつかの項目で有意な肯定的変化がみられた。精神障害に対するスティグマや偏見を低減するためには2日間の実習でも有効であることが示唆された。We conducted questionnaire surveys involving 20 university students considering a career as a registered dietitian to assess changes in their social attitudes towards those with mental disabilities,and identify factors that would facilitate their understanding of mentally disabled persons. The subjects participated in a 2-day volunteer practicum in facilities where people with mental disabilities were receiving job support services to work in a kitchen (e.g., cooking, arranging/decorating, serving, and dish washing). They were asked to complete a questionnaire prior to practicum placements (prepracticum survey), and then responded to the same questionnaire after the 2-day practicum (post-practicum survey). The pre-and post-practicum survey responses were quantified and statistically analyzed. Regarding the image of people with mental disabilities, significant positive changes were noted for some of the items related to lifestyles and relationship-building. This suggested that several days of volunteer practicum experiences, even only 2 days, was effective for mitigating stigma and prejudice attached to mental illness

Biosynthetic study of FR-900848: unusual observation on polyketide biosynthesis that did not accept acetate as origin of acetyl-CoA

The biosynthetic pathway of a potent antifungal agent, FR-900848, has been examined by administration of several 13C-labeled precursors to Streptoverticillium fervens HP-891. Although none of the 13C-labeled acetate was incorporated into FR-900848, the labeling pattern of FR-900848 derived from d-[U-13C6]glucose revealed that the fatty acid backbone of FR-900848 has been biosynthesized via a polyketide pathway. These unusual results strongly show that the major pathway to provide acetyl-CoA in this microorganism is glycolysis. Feeding experiments with d-[U-13C6]glucose, [1,3-13C2]glycerol, and l-[Me-13C]methionine provided information on the biosynthetic origin of structurally unusual parts (polycyclopropane and aminonucleoside) in this antibiotic

Cyclization mechanism of phomopsene synthase : mass spectrometry based analysis of various site-specifically labeled terpenes

Elucidation of the cyclization mechanism catalyzed by terpene synthases is important for the rational engineering of terpene cyclases. We developed a chemoenzymatic method for the synthesis of systematically deuterium-labeled geranylgeranyl diphosphate ( GGPP), starting from site-specifically deuterium-labeled isopentenyl diphosphates (IPPs) using IPP isomerase and three prenyltransferases. We examined the cyclization mechanism of tetracyclic diterpene phomopsene with phomopsene synthase. A detailed EI-MS analysis of phomopsene labeled at various positions allowed us to propose the structures corresponding to the most intense peaks, and thus elucidate a cyclization mechanism involving double 1,2-alkyl shifts and a 1,2-hydride shift via a dolabelladien-15-yl cation. Our study demonstrated that this newly developed method is highly sensitive and provides sufficient information for a reliable assignment of the structures of fragmented ions

Biosynthetic Machinery of Diterpene Pleuromutilin Isolated from Basidiomycete Fungi

The diterpene pleuromutilin is a ribosome-targeting antibiotic isolated from basidiomycete fungi, such as Clitopilus pseudo-pinsitus. The functional characterization of all biosynthetic enzymes involved in pleuromutilin biosynthesis is reported and a biosynthetic pathway proposed. In vitro enzymatic reactions and mutational analysis revealed that a labdane-related diterpene synthase, Ple3, catalyzed two rounds of cyclization from geranylgeranyl diphosphate to premutilin possessing a characteristic 5-6-8-tricyclic carbon skeleton. Biotransformation experiments utilizing Aspergillus oryzae transformants possessing modification enzyme genes allowed the biosynthetic pathway from premutilin to pleuromutilin to be proposed. The present study sets the stage for the enzymatic synthesis of natural products isolated from basidiomycete fungi, which are a prolific source of structurally diverse and biologically active terpenoids