著者

冨田 秋寛 油井 信弘 阿部 克也

出版者

日本生物工学会

雑誌

日本生物工学会大会講演要旨集

巻号頁・発行日

vol.63, 2011

著者

モタカトラ カテスワー レディ 矢島 由佳 張 ヨンチョル

出版者

日本生物工学会

雑誌

日本生物工学会大会講演要旨集

巻号頁・発行日

vol.67, 2015

著者

金桶,光起

出版者

日本生物工学会

雑誌

日本生物工学会大会講演要旨集

巻号頁・発行日

vol.平成12年度, 2000-07-10

著者

山下 道雄 松田 充功 大畑 暢敬 神田 宗和 檜垣 知臣

出版者

日本生物工学会

雑誌

生物工学会誌 : seibutsu-kogaku kaishi (ISSN:09193758)

巻号頁・発行日

vol.83, no.3, pp.123-131, 2005-03-25

参考文献数

3

被引用文献数

1

---

In 1989, in the course of our screening for new antifungal antibiotics with cell wall synthesis inhibition activity, FR901379 (WF11899A) was discovered in the culture broth of Coleophoma empetri F-11899. The strain was isolated from a soil sample collected in Iwaki city, Fukushima-prefecture, Japan. Because FR901379 had hemolytic activity, we decided to screen for semi-synthesis derivatives with low toxicity and high antifungal activity and evaluated many derivatives with substituted side chains. We started by using Actinoplanes utahensis to replace the palmitoyl group of FR901379 with other organic acids. After synthesizing several hundred organic acids and making repeated derivatives, we discovered FR131535, which had similar antifungal activity to FR901379 in vitro and in vivo and low hemolytic activity. It was not however selected as a development candidate because of insufficient antifungal activity. In the search for a more potent compound, we hypothesized that a compound with a similar molecular structure to FR131535 might produce a good antifungal drug. We therefore began the screening of Fujisawa's original acylase using a specially devised and effective screening system. After discovering "FR901379 Acylase" produced by Streptomyces sp. No. 6907, we continued with our evaluation of derivatives. We finally selected FK463 as a candidate compound for commercial drug development. In 1990, to establish an industrial manufacturing method for Micafungin (FK463), our laboratories (Fermentation Development Laboratories) commenced the following development research : (1) strain improvement of Coleophoma, (2) screening of "FR901379 Acylase"-producing strains, (3) studies to increase the scale of fermentation of FR901379 and "FR901379 Acylase", (4) determination of effective purification procedures for FR901379, a key intermediate of FR179642 and FK463, and (5) development of a HPLC assay system to measure the amount of objective compounds and impurities. Micafungin (general name, Trade mark : Funguard, Development No. : FK463) was launched in Japan on December 6, 2002. Approval in the USA and EU is pending and expected shortly.

著者

添田 愼介 明石 健志 前田 清 川北 毅

出版者

日本生物工学会

雑誌

生物工学会誌 : seibutsu-kogaku kaishi (ISSN:09193758)

巻号頁・発行日

vol.76, no.9, pp.389-397, 1998-09-25

参考文献数

11

被引用文献数

2

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Tacrolimus is an immunosuppressant macrolide isolated from Streptomyces tsukubaensis. It is used clinically to prevent the rejection of tissue transplants. To achieve the industrial production of tacrolimus, development research was aimed at breeding strains that efficiently produce tacrolimus, optimizing the cultivation conditions, determining an effective purification method, and establishing a means of rapid quantitative analysis. The wild-type S. tsukubaensis was sequentially treated with ultra violet light to furnish various types of morphologically altered mutants, from which a desired strain was selected and bred. For the fermentation of the new strain, a cultivation medium was formulated with a low viscosity and resistant to thermo-denaturation on sterilization. In a scale-up study, in which the fermentor size was increased from 30l to 25kl, the productivity of tacrolimus was found to be well reproduced by keeping both the dissolved oxygen and the agitation at low levels during the growth phase of the producing strain. As a result of these procedures, the concentration of tacrolimus in the fermentation broth was increased 300-fold over that obtaind in the early stages of the research with the wild strain. S. tsukubaensis produces many kinds of proteins and oligosacchalides as well as various types of tacrolimus related compounds. To remove these impurities effectively, the cultivation broth was directly extracted with acetone. The extract was successively purified with a high porosity absorbance resin, and acidic and natural silica gel column chromatography, followed by recrystalization in aqueous acetonitrile, to obtain tacrolimus monohydrate. Tacrolimus itself is readily converted to optical and steric isomers in an aqueous solution. When tacrolimus was analyzed by HPLC at lower temperatures, the peaks corresponding to the macrolide were complex because of cis-trans isomerization in the column. The problem was overcome by heating the column to 50℃, when the isomerization rate was so high that the peaks were fused into a single, sharp one. The epimerization ratio was found to depend on the concentration of water in the solution, but the ratio remained constant when a Brij-35 solution used as a diluent. By these procedures, a simple, rapid and reliable analytical method was established. The industrial production of tacrolimus was thus achieved by a combination of fermentation, purification, and analytical investigations.

著者

添田,愼介

出版者

日本生物工学会

雑誌

生物工学会誌 : seibutsu-kogaku kaishi

巻号頁・発行日

vol.76, no.9, 1998-09-25

---

Tacrolimus is an immunosuppressant macrolide isolated from Streptomyces tsukubaensis. It is used clinically to prevent the rejection of tissue transplants. To achieve the industrial production of tacrolimus, development research was aimed at breeding strains that efficiently produce tacrolimus, optimizing the cultivation conditions, determining an effective purification method, and establishing a means of rapid quantitative analysis. The wild-type S. tsukubaensis was sequentially treated with ultra violet light to furnish various types of morphologically altered mutants, from which a desired strain was selected and bred. For the fermentation of the new strain, a cultivation medium was formulated with a low viscosity and resistant to thermo-denaturation on sterilization. In a scale-up study, in which the fermentor size was increased from 30l to 25kl, the productivity of tacrolimus was found to be well reproduced by keeping both the dissolved oxygen and the agitation at low levels during the growth phase of the producing strain. As a result of these procedures, the concentration of tacrolimus in the fermentation broth was increased 300-fold over that obtaind in the early stages of the research with the wild strain. S. tsukubaensis produces many kinds of proteins and oligosacchalides as well as various types of tacrolimus related compounds. To remove these impurities effectively, the cultivation broth was directly extracted with acetone. The extract was successively purified with a high porosity absorbance resin, and acidic and natural silica gel column chromatography, followed by recrystalization in aqueous acetonitrile, to obtain tacrolimus monohydrate. Tacrolimus itself is readily converted to optical and steric isomers in an aqueous solution. When tacrolimus was analyzed by HPLC at lower temperatures, the peaks corresponding to the macrolide were complex because of cis-trans isomerization in the column. The problem was overcome by heating the column to 50℃, when the isomerization rate was so high that the peaks were fused into a single, sharp one. The epimerization ratio was found to depend on the concentration of water in the solution, but the ratio remained constant when a Brij-35 solution used as a diluent. By these procedures, a simple, rapid and reliable analytical method was established. The industrial production of tacrolimus was thus achieved by a combination of fermentation, purification, and analytical investigations.

著者

栗山 一秀 芦田 晋三 斉藤 義幸 秦 洋二 杉並 孝二 今安 聰

出版者

日本生物工学会

雑誌

醗酵工学会誌 (ISSN:03856151)

巻号頁・発行日

vol.64, no.3, pp.p175-180, 1986-05

被引用文献数

1

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It has been believed that in sake ethyl caproate is one of the main component of ginjo-flavour. There have been no reports about the synthesis and hydrolysis of ethyl caproate. We have studied the activity of sake yeast in the synthesis and hydrolysis of ethyl caproate. The results obtained are as follows : 1) The esterase of Saccharomyces cerevisiae on ethyl caproate synthesis was separated into three fractions (S-I, II, III) by Sepharose 6B gel filtration. 2) The esterase fraction of ethyl caproate synthesis (S-II, III) did not hydrolyze p-nitrophenyl acetatte, so it was impossible to examine the esterase activity by this method. The esterase activity of ethyl caproate synthesis and hydrolysis must be measured by gas chromatography.3) The optimum pH of the esterase of ethyl caproate synthesis was 5.0,and that of ethyl caproate hydrolysis was 10.0. 4) The optimum pH of alcohol acyltransferase was 8.0. 5) There were differences in the localization of esterase and alcohol acyltransferase in the cells. Therefore, there are two pathways to the formation of ethyl caproate through esterase and through alcohol acyltransferase.6) The esterase fraction S-II was stabilized by ammonium sulfate.

著者

前田 剛志 加藤 未来 栗原 甘奈 能木 裕一 浜本 牧子

出版者

日本生物工学会

雑誌

日本生物工学会大会講演要旨集

巻号頁・発行日

vol.67, 2015

著者

篠田 直 梶山 満里子 山本 直之

出版者

日本生物工学会

雑誌

日本生物工学会大会講演要旨集

巻号頁・発行日

vol.18, 2006

著者

上野 義栄 平賀 和三 森 義治 小田 耕平

出版者

日本生物工学会

雑誌

生物工学会誌 : seibutsu-kogaku kaishi (ISSN:09193758)

巻号頁・発行日

vol.85, no.3, pp.109-114, 2007

参考文献数

30

被引用文献数

4

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古来の発酵法を用いて製造した京漬物,千枚漬けよりγ-アミノ酪酸(GABA)を高生産する乳酸菌が分離され,Lactobacillus sp. L13と同定,命名した.本菌は,増殖にグルタミン酸を要求し,高濃度のグルタミン酸存在下でGABAを高生産した.培養液のpHを酸性(pH5)に維持すると, 800mMのグルタミン酸ナトリウムより81%の変換率で,最大650mM (6.7%)のGABAを生産した.この乳酸菌をスターター菌として使用し,GABAを0.1%含有した千枚漬けを試作した.官能評価の結果,従来の製品よりも風味のすぐれた千枚漬けの製造が可能であることが示された.

著者

江邉,正平

出版者

日本生物工学会

雑誌

日本生物工学会大会講演要旨集

巻号頁・発行日

vol.67, 2015-09-25

著者

人見,将郎

出版者

日本生物工学会

雑誌

日本生物工学会大会講演要旨集

巻号頁・発行日

vol.平成13年度, 2001-08-24

著者

東端 啓貴

出版者

日本生物工学会

雑誌

生物工学会誌 : seibutsu-kogaku kaishi (ISSN:09193758)

巻号頁・発行日

vol.91, no.2, pp.96-100, 2013

参考文献数

37

著者

廣瀬 遵

出版者

日本生物工学会

雑誌

生物工学会誌 : seibutsu-kogaku kaishi (ISSN:09193758)

巻号頁・発行日

vol.75, no.4, 1997

参考文献数

4

著者

小路 博志

出版者

日本生物工学会

雑誌

生物工学会誌 : seibutsu-kogaku kaishi (ISSN:09193758)

巻号頁・発行日

vol.90, no.5, pp.238-241, 2012

被引用文献数

1

著者

柴垣 奈佳子 カルタヘナ ジョイス 田畑 哲之 兼松 泰男 伊東 一良 福井 希一

出版者

日本生物工学会

雑誌

日本生物工学会大会講演要旨集

巻号頁・発行日

vol.21, 2009

著者

山本 秀策

出版者

日本生物工学会

雑誌

生物工学会誌 : seibutsu-kogaku kaishi (ISSN:09193758)

巻号頁・発行日

vol.81, no.11, 2003-11-25