新型强效免疫抑制剂F904的结构测定

分析吸水链霉菌 (Streptomyces hygroscopicus) FC90 4产生的具有免疫抑制活性的化合物 F90 4的理化性质及光谱学性质 (UV、IR、NMR、X- Ray衍射 ) ,证实化合物 F90 4的分子结构及空间构型与西罗莫司(sirolimus,又称 rapamycin)同质。     

日本抗生素研究动向

本文对1986年日本国内发表的抗生素论文163篇和专利114份进行综述.β-内酰胺抗生素类在寻找抗霉菌药时发现吸水链霉菌产生六种Clavam物质.从吸水链霉菌NRRL15846的培养液中分离到Clavamycins A、B和C,从吸水链霉菌NRRL15879培养液中分离到Clavamycin D、E和F.它们的结构见图1所示.Clavamycins对细菌无作用,     

吸水链霉菌FC-904发酵代谢产物29-O-去甲基雷帕霉素的分离和结构鉴定

目的 从西罗莫司产生菌吸水链霉菌FC904的发酵液中分离纯化代谢产物FIM-R85，鉴定其化学结构。方法 采用硅胶柱层析和制备液相分离纯化获得FIM-R85，进行理化性质以及NMR、UV、IR和HRMS等波谱分析，鉴定其化学结构。 结果 纯化获得HPLC纯度为98.7%的FIM-R85，其为西罗莫司类似物，与29-O-去甲基雷帕霉素同质。结论 29-O-去甲基雷帕霉素为西罗莫司产生菌吸水链霉菌FC904的发酵代谢产物之一。     

链霉菌FM41产生的克拉维烷类新化合物—β—内酰胺酶抑制剂FM41

自福州土壤分离的β—内酰胺酶抑制剂ＦＭ４１产生菌，链霉菌ＦＭ４１经形态、培养特征和生理特性与克拉维酸产生菌俸状链霉菌直接对照比较，证明链霉菌ＦＭ４１与棒状链霉菌十分相似。链霉菌ＦＭ４１的代谢产物ＦＭ４１经理化性质和体外生物学活性研究，表明它与克技维酸和已知的克拉维烷类化合物不同，可能是克拉维烷类中的新成员，其化学结构正在研究中。     

强效免疫抑制剂西罗莫司类似物FIM-Rap-02的分离与鉴定

从西罗莫司产生菌吸水链霉菌突变株FC904-30的发酵产物中,分离纯化获得西罗莫司类似物FIM-Rap-02的晶体。对FIM-Rap-02进行理化性质、光谱等分析,并通过单晶X-Ray衍射确定构型,结果证实它的结构与prolylrapamycin同质。     

国产抗真菌抗菌素球红霉素的药理研究

福建省微生物研究所于1970年从江西省南昌市土壤中分离的一株:链霉菌(编号414),经鉴定为链霉菌属中的一个新种,定名为球孢玫瑰紫链霉菌(Str.bloboroseodillaceusn.sp),它产生的抗菌素属于七烯类曲古霉素族的化合物。     

聚醚类抗生素的研究——Ⅰ.Lonomycin A产生菌SIPI-A4-0040的分类与鉴定

从我国海南省琼中县土壤中分离得到一株链霉菌,编号SIPI-A4—0040,它对革兰氏阳性有强烈抑制作用,经鉴别活性物质为聚醚类抗生素Lonomycin A。该菌孢子丝螺旋形,孢子表面多皱,基丝灰粉,气丝浅灰至棕红,吸水后呈褐湿斑,可溶色素土黄至粉灰。在培养特征和生理生化特性上,与已知的吸水链霉菌相似但有一定差别,故定名为吸水链霉菌琼中亚种(Streptomyces hygroscopicus subsp.Qiong Zhong n.subsp.)。     

哥斯达黎加链霉菌抗菌成分的活性跟踪分离与鉴定

目的 分离、鉴定哥斯达黎加链霉菌(Stretomyces costaricanus)发酵液中的抗菌活性成分。方法 通过活性跟踪,采用硅胶柱层析等方法对哥斯达黎加链霉菌次生代谢产物进行分离纯化。采用光谱分析对活性成分进行结构解析。结果 哥斯达黎加链霉菌中的抗菌活性成分为放线菌素D。结论 首次发现放线菌素D对香蕉枯萎镰刀菌4号生理小种(Fusarium oxysporum f.sp.cubense Face 4,Focr4),金黄色葡萄球菌(Staphyloccocus aureus)和耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcus aureus,MRSA)有较强的抑制活性。     

螺旋链霉菌U-1941中PKSⅡ型基因在淡青链霉菌tcmK变异株中的克隆(Ⅰ)

利用螺旋霉素产生菌螺旋链霉菌（Streptomyces spiramyceticus U-1941）中发现的PKSⅡ型基因，经测序和同源性比较证明在4174bp片段中含有PKSⅡ型KS（KSα）基因，该基因（pCG4-K，aspA）由1229bp组成编码432个氨基酸，与产二素链霉菌AlpA和淡青链霉菌TcmK同源性分别为74．4％和69．7％。将含aspA基因的重组质粒pCG4在四并菌素（tetracenomycin C）产生菌（S．glaucescens GLA4—26）tcmK基因缺陷型变异株中进行克隆，TLC分析表明转化子的发酵产物比对照株多一个明显的黄色斑点，该物质经分离、提纯后分析确定为一个含苯式结构的小分子化合物AS-5。     

一种自然产生的红霉素:红霉素F

一株红霉素链霉菌(Streptomyces ery-threus)菌株培养液经提取结晶滤去主要红霉素后的母液中分离出一种叫做红霉素F的新的红霉素。分离过程是将结晶母液样品(15g),放在装有C18柱的Waters Prep System 500的高压液相层析仪上进行层析。溶媒系统的     

西罗莫司同分异构体Rap-D1的分离与鉴定

从西罗莫司产生菌的突变株FC904-25的发酵产物中分离获得化合物Rap-D1的晶体。对其理化性质包括UV、IR、LC-MS、NMR谱等进行分析，结果表明Rap-D-与西罗莫司为同分异构体，具有相同的平面结构。通过单晶X-衍射确定了构型，它与文献报道经化学半合成获得的28-epirapamyein同质。     

雷帕霉素二醛的分离和结构鉴定…杨国新，陈夏琴，余辉，等(450)

目的 从雷帕霉素产生菌吸水链霉菌FC904的发酵粗提物中，分离纯化在HPLC图谱中与雷帕霉素相对保留时间(RRT)为0.88的化合物FIM-R24并鉴定其化学结构。方法 采用硅胶柱层析和制备液相分离FIM-R24，并对其进行NMR、UV、IR和HRMS等波谱分析。用SRB测定化合物体外抗肿瘤活性，用沙氏液体培养基二倍稀释法测定化合物的抗真菌活性。结果与结论 FIM-R24的结构为雷帕霉素二醛。FIM-R24的抗肿瘤活性仅比雷帕霉素略低，抗酵母样真菌的活性仅为雷帕霉素的1/8~15。     

Mutagenesis of the rapamycin producer Streptomyces hygroscopicus FC904

Rapamycin (RPM) is produced by Streptomyces hygroscopicus FC904 isolated from soil in Fuzhou, China. It is a triene macrolide antibiotic with potential application as an immunosuppressant and drug for human gene therapy. In an attempt to improve rapamycin production, mutation and screening of the parent culture have been carried out. Thousands of survivors were obtained after mutagenesis by NTG (3 mg/ml) and UV (30 W, 15 cm, 30 seconds) of spore suspensions. None showed improved production of RPM. We determined the susceptibility to antibiotics of S. hygroscopicus FC904 by two fold dilutions of antibiotics in oatmeal agar plates. It was found that the strain was resistant to penicillin, erythromycin, RPM, tetracycline and chloramphenicol, but susceptible to mitomycin C (MIC, 10 microg/ml) and aminoglycosides such as gentamicin (MIC, 0.1 microg/ml), kanamycin (MIC, 0.1 microg/ml) and streptomycin (MIC, 0.3 microg/ml). Protoplasts of strain FC904 were prepared after finding the best conditions for their formation. They were treated with gentamicin, erythromycin, mitomycin C and NTG. Surprisingly, gentamicin was especially effective for obtaining higher RPM-producing mutants. Mutant C14 was selected by exposing the protoplasts of the parent strain FC904 to 1 microg/ml of gentamicin at 28 degrees C for 2 hours. A higher RPM-producing mutant (C14-1) was obtained from the protoplasts of mutant C14 treated with gentamicin, and its titer was 60% higher than that of the parent strain FC904 by HPLC analysis. Another improved mutant (C14-2) was obtained from the spores of mutant C 14 treated with 1 microg/ml of gentamicin plus 2 mg/ml of NTG at 28 degrees C for 2 hours. Mutant C14-2 had a titer 124% higher than FC904. The possible mechanism for the effect of gentamicin by using protoplasts or spore suspensions will be discussed, i.e. the possibility of gentamicin being a mutagen or a selective agent.     

西罗莫司高产突变株FC904-33

西罗莫司是吸水链霉菌FC904产生的新型强效免疫抑制剂。为了获得高产西罗莫司突变株,采用UV、硝苯胍和甲基磺酸乙酯诱变剂诱变处理吸水链霉菌FC904的孢子悬液和发芽孢子,随后用西罗莫司对存活菌株进行自身代谢产物的耐受性试验,获得西罗莫司高产突变株FC904-33,其生物合成能力是原出发菌株的4.6倍。本文报道该突变株的培养特征、对抗生素的敏感性、西罗莫司生产能力和副产物等。     

免疫抑制剂SIPI-96-1014的分离和鉴别

在应用酵母突变体模型筛选免疫抑制过程中，筛选出一阳性菌株ＳＩＰＩ－９６－１０１４。经过发酵提取，分离和纯化，从其菌丝体中分离出一个活性化合物ＳＩＰＩ－９６－１０１４。通过对其理化性质等光谱数据的分析，确定其结构与化合物邻羟基乙酰苯胺一致。生物学活性研究表明，其对酵母野生株和突变株具有一定的抑制活性，详细的免疫抑制活性有待于进一步研究。     

FR-900520 and FR-900523, novel immunosuppressants isolated from a Streptomyces. II. Fermentation, isolation and physico-chemical and biological characteristics

FR-900520 and FR-900523, novel neutral macrolide immunosuppressants, were isolated from the cultured broth of Streptomyces hygroscopicus subsp. yakushimaensis No. 7238. Their molecular formulae were determined as C43H69NO12 and C42H67NO12, respectively. The compounds suppressed immune response in vitro. IC50 values of FR-900520 and FR-900523 for mouse mixed lymphocyte reaction were 0.55 nM and 1.6 nM, respectively. FR-900520, the major component, clearly prolonged skin allograft survival in rats.     

3L自动发酵罐中西罗莫司的发酵研究

采用美国NBS公司生产的BIOFLO3000型3L发酵罐进行西罗莫司发酵代谢过程的考察和代谢参数的累积,建立了较为适应的西罗莫司发酵条件,罐上发酵水平与摇瓶发酵水平相当.     

Novel antitumor antibiotic phospholine. 1. Production, isolation and characterization

Phospholine was isolated as an antitumor antibiotic from the fermentation broth of Streptomyces hygroscopicus. Phospholine is an amphoteric compound which has an amino group and a phosphoric acid ester as functional groups. Phospholine shows strong activities against L1210, P388 and EL-4.