短刺小克银汉霉AS 3.970对川丁特罗的微生物转化

目的对川丁特罗进行微生物转化研究。方法利用短刺小克银汉霉Cunninghamella.blakesleana AS 3.970对川丁特罗进行微生物转化,通过柱层析、液相色谱-质谱及核磁技术对川丁特罗微生物转化产物进行分离与鉴定。结果短刺小克银汉霉Cunninghamella.blakesleana AS 3.970转化川丁特罗累计获得三个转化产物,分别是川丁特罗芳香羟胺代谢物、川丁特罗叔丁基羟基取代代谢物和1-羧基川丁特罗。结论通过微生物转化技术可以对川丁特罗进行微生物结构修饰。     

海洋毛霉属真菌Mucor sp.MNP801转化天然香豆素后的挥发性成分研究

目的运用实验室保藏的海洋真菌Mucor sp.MNP801转化6,7-二甲氧基香豆素,以期望进一步得到新的活性物质的研究。方法运用海洋真菌对特定的天然产物进行生物转化,并借助于GC-MS等手段分析转化组与对照组培养基的乙酸乙酯萃取物的差别。结果发现转化组中出现对照组没有且异于加入底物的新产物2-乙酰-4-乙酰氨基-5-硝基苯酚,为首次从海洋毛霉属真菌中发现的产物。结论运用海洋微生物对天然产物进行代谢,对开发新的活性物质有一定的意义。     

短刺小克银汉霉菌对马兜铃酸A的代谢转化

选取短刺小克银汉霉菌（Cunninghamella blakesleana AS3．910）用微生物转化的方法对马兜铃酸A（Aristolochic acid）进行了代谢转化研究并比较，微生物转化产物和哺乳动物体内的代谢产物的异同。考察了影响微生物转化产物形成的各种因素，并对该转化体系进行了优化，采用高效液相色谱、质谱对代谢产物进行了检测和分析。多种因素条件会对微生物的转化产生影响，发酵液中主要的转化产物是马兜铃酸A的O去甲基化物，该产物和报道的NSL动物在摄入马兜铃酸A后尿中发现的一种代谢产物结构相同。利用小克银汉霉菌的转化可以方便地制备马兜铃酸A在哺乳动物体内的某些代谢产物，它可以作为研究马兜铃酸A代谢物的一个体外模型进行探索。     

人参皂苷生物转化的研究进展

目的综述人参皂苷在体内及体外的生物转化研究概况。方法查阅国内外相关文献,以其中的26篇文献为依据对人参皂苷在体内的转化途径及产物加以介绍,也对体外转化中使用的酶法和微生物法加以详细阐述。结果人参皂苷在体内被代谢成为多种稀有人参皂苷,它们是人参在体内发挥药理活性作用的物质。体外生物转化人参皂苷的方法较多,并取得了许多有意义的成果。结论为人参皂苷的代谢研究及稀有人参皂苷的体外生物转化制备提供了参考。     

短刺小克银汉霉AS 3.970对白鲜碱的微生物转化

目的 采用短刺小克银汉霉AS 3.970(C.blakesleana AS 3.970)对白鲜碱展开微生物转化研究。方法 利用30株丝状真菌对白鲜碱进行微生物转化,筛选出转化效果好的菌株;然后在该菌株微生物转化试验中考察接种量、转化温度、培养基pH值、转化时间等不同因素对白鲜碱微生物转化作用的影响,选择出最优的转化条件;在最优转化条件下,规模制备白鲜碱的微生物转化产物并进行结构鉴定。结果 短刺小克银汉霉AS 3.970对白鲜碱的微生物转化效果好,在微生物转化研究中发现白鲜碱转化的最优条件是转化温度为28℃,培养基初始pH值为7.0,最适接种量5%(体积分数),转化时间为7 d;通过分离纯化和结构鉴定,最终得到两个主要转化产物,分别是4-甲氧基-2,3-二氢呋喃喹啉与3-(2-羟乙基)-4-甲氧基喹啉酮。结论 通过微生物转化技术可以对白鲜碱进行微生物结构修饰。     

哺乳动物代谢的微生物模型

由于哺乳动物产生的药物代谢产物往往仅有痕量,故难以测定其化学结构和生物活性。本文综述应用微生物模拟哺乳类代谢过程,使产生足量的药物代谢产物,以供用于药理研究。微生物转化微生物转化即指微生物系统对各种化学物     

人体微生物天然产物研究进展

得益于基因测序技术、微生物组学研究和生物信息学分析手段的快速发展，人体微生物天然产物研究近年来取得了长足的进展。随着研究的深入，人们发现人体微生物天然产物往往会参与产生菌与宿主或与其他人体微生物之间的相互作用，可以直接或间接地影响人体健康。相应地，不少人体微生物天然产物展现出良好的成药性或作为疾病诊疗新型标志物的潜力。因此，研究人体微生物天然产物不仅能够拓展活性天然产物的来源，促进药物研发，而且在疾病诊断和改善人体健康方面具有重要的意义。综述了人体微生物天然产物研究常用的3类策略，并着重介绍了一些具有代表性的化合物的发现方法及其多样的结构与活性，以期为相关方向的进一步深入研究提供参考。     

人参皂苷的微生物转化研究进展

研究表明人参稀有皂苷具有很强的生物活性,为获得稀有人参皂苷的各种研究越来越多,而生物转化法制备稀有人参皂苷已成为一条重要途径。本文对产稀有人参皂苷微生物转化的方法最新研究进展进行了简要的综述,并简要展望了人参皂苷生物转化研究的前景。     

Advances in the Study of Biotransformation of Ginsenoside by Microorganisms

研究表明人参稀有皂苷具有很强的生物活性,为获得稀有人参皂苷的各种研究越来越多,而生物转化法制备稀有人参皂苷已成为一条重要途径.本文对产稀有人参皂苷微生物转化的方法最新研究进展进行了简要的综述,并简要展望了人参皂苷生物转化研究的前景.     

微生物转化在药学中的应用

目的对近十年来微生物转化在药学研究和工业生产中的应用及发展进行综述。方法在查阅国内外文献的基础上,简介了微生物转化的几种主要化学反应和微生物转化在手性药物合成、药物代谢及天然药物中的应用。结果与讨论通过综述微生物转化在药学研究和生产中的应用,说明了微生物转化的重要性及广阔的发展前景。     

Thoughts and facts about antibiotics: Where we are now and where we are heading

The declining trends in microbial metabolite and natural products research and the refocusing of this research area are discussed. Renewing natural products research requires inexhaustible natural resources, as well as new genetic techniques and microbial sources, including endophytic microbes. The numbers of known bioactive metabolites are summarized according to their microbiological origin, biological activities and chemical structures. Synthetic and natural product-based libraries are also compared. Importantly, the wide range of microbial metabolite bioactivities, future trends and the importance of prioritizing natural products over synthetic compounds are emphasized.     

Application of microbial biotransformation for the new drug discovery using natural drugs as substrates

This review describes microbial transformation studies of natural drugs, its importance in correlating them with the corresponding metabolism (biotransformation) in animal system and in the structural modification of complex drug molecules, which are difficult to obtain synthetically. Emphasis is laid on the potential microorganisms, which mimic the pathways of mammalian metabolism and which involve in stereoselective, regiospecific and selective conversions of natural drugs to their derivatives by microorganisms, which are more useful and difficult to synthesize. This paper describes the present state-of-art, will elucidate the additional possibilities with microbial biotransformation of natural drugs, i.e., comparison of microbial transformation with mammalian metabolism and possibility of producing novel molecules, which are difficult to produce by other means.     

Natural Products in Drug Discovery and Development. 27-28 June 2005, London, UK

The meeting covered many aspects of the use of natural products in drug discovery and development. The historical and current contributions of natural products to the main classes of medicines, technical improvements to the supply of marine microbial products by fermentation and molecular biology and the value of natural chemical diversity for providing patentable, drug-like lead molecules were among the topics discussed. Several compounds in current clinical trials were described; these included several anticancer compounds and two compounds in development by Phytopharm plc, PYM-50028 (Cogane) and PYM-50018 (Myogane), for the treatment of neurodegenerative disease.     

The historical delivery of antibiotics from microbial natural products--can history repeat?

Microbial natural products are the origin of most of the antibiotics on the market today. However, research in antibiotics and natural products has declined significantly during the last decade as a consequence of diverse factors, among which the lack of interest of industry in the field and the strong competition from collections of synthetic compounds as source of drug leads. As a consequence, there is an alarming scarcity of new antibiotic classes in the pipelines of the pharmaceutical industry. Still, microbial natural products remain the most promising source of novel antibiotics, although new approaches are required to improve the efficiency of the discovery process. The impact of microbial biodiversity, the influence of growth conditions on the production of secondary metabolites, the choice of the best approach at the screening step and the challenges faced during the isolation and identification of the active compounds are examined in this review as the critical factors contributing to success in the effort of antibiotic discovery from microbial natural products.     

微生物天然产物生物及化学信息学最新进展

摘要：微生物天然产物一直是药物开发的重要源泉，而且目前仍是新结构天然产物的重要来源。但随着微生物天然产物基数的增加，重复发现已经成为制约其发展的主要因素，而基于生物信息学和化学信息学建立起来的基因组挖掘技术是解决这一问题的关键。近年来天然产物相关信息学研究一直处于加速发展阶段，为了使天然产物研究者能够及时了解并选择性使用这些信息学工具，以提高新化合物的发现效率，本文对近两年来微生物天然产物研究领域相关的信息学工具进行了综述。     

Unusual microbial lactonization and hydroxylation of asiatic acid by Umbelopsis isabellina

Asiatic acid (1) is a natural triterpenoid isolated from Centella asiatica. This paper reports the microbial transformation of asiatic acid by an endophytic fungus Umbelopsis isabellina to obtain derivatives potentially useful for further studies. Incubation of asiatic acid with U. isabellina afforded two derivatives 2α,3β,7β, 23-tetrahydroxyurs-12-ene-28-oic acid (2) and 2α,3β,7β,23-tetrahydroxyurs-11-ene-28,13-lactone (3). The structures of these compounds were elucidated by spectral data. Compound 3 has formed an unusual lactone. These two products are new compounds. The possible transformation passway was also discussed.     

Microbial biotransformation of kurarinone by Cunninghamella echinulata AS 3.3400

In this paper, microbial transformation of kurarinone (1) by Cunninghamella echinulata AS 3.3400 was investigated and four transformed products were isolated and identified as 6″-hydroxykurarinone (2), 4″,5″,8″-trihydroxynorkurarinone (3), norkurarinone (4), and kurarinone-7-O-β-glucoside (5), respectively. Among them, 3 and 5 are new compounds, and the rare glycosylation in microbial transformation was observed. In addition, the cytotoxicities of transformed products (2–5) were also investigated.     

Natural products from cyanobacteria: Exploiting a new source for drug discovery

In the 1990s, the pharmaceutical industry shifted its focus to a combinatorial chemistry approach to fill drug-discovery pipelines; however, more recently there has been renewed interest in natural products as sources of lead compounds. Cyanobacteria are prolific producers of natural products displaying enormous chemical diversity, yet, until recently, exploitation of the genera was hampered by a number of issues related to their handling. With most of these problems now resolved, cyanobacteria have the potential to expand the variety of natural products obtained from microorganisms. The relative disregard in the past of cyanobacteria compared with other microbial sources of natural products, as well as the huge chemical diversity and biological activities of their products, recommend them as an attractive source of novel drugs for use in diverse therapeutic areas.     

微生物天然产物数据库的建立及应用

微生物天然产物数据库（microbial natural products database，MNPD）是由中国医学科学院医药生物技术研究所和创腾科技有限公司联合开发，在MDL ISIS Base化学信息管理系统上构建的综合性天然产物数据库。包括15000多个微生物天然产物的来源、制备、理化性质、二维和三维化学结构、生物活性和原始文献等信息资料，可用于微生物天然产物的信息查询、总结性检索和计算机辅助药物分子设计研究。微生物天然产物数据库是医药领域科研工作者开展药物研发及相关工作的重要工具。本文简要介绍了数据库的开发历程、组成、功能及一些应用实例。     

具有烯二炔类抗生素产生能力的稀有放线菌的筛选

高质量的微生物天然产物库是新药研发的重要来源,目前我国已经建立了较大规模的微生物产物库,建立高效准确的筛选模型来筛选烯二炔类抗肿瘤抗生素对已建立的微生物产物库进行筛选对于新药研发至关重要.本文重点讨论了目前已经较为常用的烯二炔类抗生素产生菌的筛选方法,包括基于活性与基因的筛选模型和精原细胞筛选模型,之后根据甄永苏院士的团队所做的内容提出两种新的理论上可行而且未来有可能被构建的筛选模型.