天然活性先导化合物生物转化研究进展

天然活性先导化合物生物转化是利用生物催化剂(如：酶、微生物、动植物细胞)将加入到生物反应系统中的天然活性先导化合物进行特异性的分子结构修饰以获得高效、低毒新化合物的方法。该方法可以有效地提高已知的天然活性先导化合物的活性、降低毒副作用、改善水溶性和生物利用度,也可以用来生产具有重要应用价值的微量天然活性先导化合物,同时可用于药物代谢机制的研究。国内外学者已经针对甾体、醌类、黄酮类、萜类等化合物开展了天然活性先导化合物生物转化研究,筛选出一批有重要应用价值的生物转化反应类型,但针对天然活性先导化合物生物转化的机制、生物转化过程工程以及生物转化产物活性等方面的研究较少。将现代生命科学技术(如：生物催化剂的定向改造、高通量筛选、组合生物转化、非水相生物转化)引入天然活性先导化合物生物转化研究中,必将推进天然活性先导化合物的快速发展。     

天然产物的生物转化

本文按反应类型综述了近五年来天然产物生物转化的研究进展,并对生物技术干预下的生物转化作了简要介绍.     

天然活性多肽的研究进展

综述了近年来天然来源的活性多肽的研究近况,主要侧重直链肽的研究近况,包括人,动物,植物来源多肽的提取分离方法,氨基酸组成以及生物活性等方面的研究进展。     

手性药物合成中的生物转化

目前手性药物的发展非常迅速,本文介绍了利用微生物及其酶系作为生物催化剂,进行外消旋底物的拆分或前手性底物的不对称化,以合成手性药物的生物转化方法;并评述了生物转化在合成手性药物这一领域的应用现状及今后的发展趋势。     

二氢杨梅素结构修饰及生物活性研究进展

二氢杨梅素是一种二氢黄酮醇,具有抗菌、抗炎、抗肿瘤以及保肝护肝等多种生物活性。由于其结构中的6个羟基导致其脂溶性差及生物利用度低,因此对其进行结构修饰以期提高生物利用度和生物活性。本文综述了二氢杨梅素的化学法结构修饰及其生物活性等研究工作,化学修饰方法涉及醚化反应、酯化反应和金属配合物等方法,合成的衍生物具有抗病毒、抗菌、抗氧化、神经保护以及抑制肿瘤细胞增殖等活性,并且提出二氢杨梅素结构修饰过程中存在的挑战及发展方向,为更好地开发二氢杨梅素衍生物提供技术服务。     

大豆异黄酮微生物转化研究进展

大豆异黄酮是大豆在其生长过程中形成的一类次生代谢产物,具有抗氧化、抗癌、减少骨质流失、降低心脑血管发病率等多种生理功能。目前已知,被摄人机体的大豆异黄酮将被肠道微生物菌群转化为具有更高、更广生物学活性的不同产物。因此,大豆异黄酮对人体的有益调节作用强弱并不简单取决于摄人机体的净含量的多少,更在于被摄人机体的大豆异黄酮将如何被肠道菌群转化。本文从大豆异黄酮的组成与功能、大豆异黄酮体内吸收、代谢及微生物转化、转化产物的活性以及高效合成等方面进行了系统综述,对大豆异黄酮微生物生物转化研究现状和存在问题进行分析总结,并对今后发展趋势进行展望,旨在推动高活性大豆异黄酮微生物转化产物的研究与开发。     

手性药物合成中的生物转化

目前手性药物的发展非常迅速,本文介绍了利用微生物及其酶系作为生物催化剂,进行外消旋底物的拆分或前手性底物的不对称化,以合成手性药物的生物转化方法;并评述了生物转化在合成手性药物这一领域的应用现状及今后的发展趋势。     

天然多糖分子修饰研究进展

多糖衍生物因其在生物学上的重要作用引起了科学家们的高度重视。近年来,国内外在多糖的分子修饰方法、多糖衍生物的药理学、结构与功能关系、临床应用上的研究已取得很大进展。本文综述了近年来国内外多糖的分子修饰方法及其衍生物的生物活性研究,并对其应用前景进行展望。     

植物甾醇微生物转化制备甾体药物中间体的研究进展

微生物选择性降解植物甾醇侧链获取甾体药物合成的重要中间体雄甾-4-烯-3,17-二酮（4-AD）和雄甾-1,4-二烯-3,17-二酮（ADD）对于我国制药行业具有重要意义。现存文献资料对该领域缺乏全面系统的分析总结,从甾醇侧链微生物转化的机理、途径及其收率的影响因素等几个方面综述了近几年的研究进展,并对此领域的发展趋势进行了展望。     

天然药物抗HIV 机制的研究进展

艾滋病是威胁人类健康的重大传染性疾病,目前仍未有令人满意的治疗方法。近年来的研究发现,天然药物具有广泛的抗HIV药理学活性,如免疫调节、抑制HIV复制中相关功能酶、抗氧化等。本文就天然药物抗HIV的相关作用机制展开综述。     

石杉碱甲结构改造的研究进展

石杉碱甲是高效、高选择性的可逆性乙酰胆碱酯酶抑制剂,是治疗早老性痴呆症的一个有前景的药物.本文概述了石杉碱甲的性质、结构和构效关系,从结构简化、C10、吡啶酮环、脂桥环、环外双键和桥头氨基等方面综述了石杉碱甲结构改造的研究进展,并描述了所得的新型石杉碱甲类似物的抗乙酰胆碱酯酶的生物活性.在已合成的大量的石杉碱甲类似物中,部分类似物的活性优于天然石杉碱甲,石杉碱甲结构改造的研究取得了可喜的进展.     

利奈唑胺C 环结构改造研究进展

首个唑烷酮类抗菌药利奈唑胺自2000 年上市以来,其耐药性问题日趋严重,开发新型唑烷酮类抗菌药物成为研究热点之一。综述了近年来对利奈唑胺C 环进行的结构改造及相关衍生物的研究进展,旨在为唑烷酮类抗菌药的深入研发提供参考。     

Enzyme Modification by Natural Chemical Chaperons of Microorganisms

We demonstrated for the first time that alkyl hydroxybenzenes (the d₁ microbial autoregulatory factors involved in stress responses of cells) are capable of stabilizing enzymes in aqueous media and increasing their catalytic activity. The stabilizing effect of a chemical analogue of alkyl hydroxybenzenes, C₇-AHB, was established in in vitro studies with enzymes of microbial origin: a protease produced by Bacillus licheniformis, cellulase produced by Trichoderma viride, and -amylase produced by Bacillus subtilis. This effect manifested itself in considerable extension of the temperature and pH ranges of the enzymatic activity. The modulation of the catalytic activities of the stabilized enzymes depended on the C₇-AHB concentration and on the time of preincubation of the complexes obtained. We demonstrated that not only enzymes but also their polymeric substrates formed complexes with C₇-AHB and this significantly influenced the efficiency of hydrolytic reactions. We also conducted comparative studies on the efficiency of hydrolytic reactions in systems in which the structure of enzymes and/or substrates was modified with C₇-AHB.     

木霉属真菌的生物降解及生物转化作用研究进展

木霉（Trichoderma spp．）属于半知菌亚门、丝孢纲、丝孢目,粘孢菌类,是一类具有很大应用生产潜力的真菌,目前国际上已查明并命名的木霉属真菌,共计60种和2个变型,国内正式发表的木霉菌有10种,记录种名20个。木霉属真菌的生物降解、转化功能与分泌纤维素酶、葡聚糖酶、几丁质酶、脂肪酶、木聚糖酶等酶的能力相关,综述了木霉属真菌生物降解和生物转化底物及其他方面的研究进展。     

结构修饰提高酶稳定性、活性

酶因其特异性和可持续性而成为广泛应用的绿色催化剂，其稳定性和催化活性是决定酶适用性的关键因素。为满足实际应用需求，通过蛋白质结构修饰赋予其所需的催化特性是当前的研究热点。提高热稳定性的策略有：引入非共价/共价相互作用（疏水相互作用、氢键、盐桥、芳香环相互作用、二硫键）、环截短、C端和N端工程，及增加脯氨酸/减少甘氨酸的数目等；获得具有高效性和多样性的生物催化剂的策略有：降低空间位阻、拓宽催化口袋、增加底物亲和力及调节活性位点灵活性等。然而，在稳定性或催化功能改造的过程中，新突变的引入会削弱其他功能，致使进化过程中稳定性和催化活性相互制约。因此，采用基于理性计算优选突变热点、基于多重蛋白质稳定性或活性改造策略的共进化，以及基于高度稳定的蛋白质骨架创造或/和优化蛋白质功能等多种策略克服酶稳定性-活性之间的权衡。本综述重点阐述了结构修饰方法在提高酶稳定性或/和催化活性方面的应用，并展望了该领域的未来发展前景。     

Research Progress on the Structural Modification of Magnolol and Honokiol and the Biological Activities of Their Derivatives

Magnolol and Honokiol are the primary active components that have been identified and extracted from Magnolia officinalis, and several investigations have demonstrated that they have significant pharmacological effects. Despite their therapeutic benefits for a wide range of illnesses, research on and the implementation of these compounds have been hindered by their poor water solubility and low bioavailability. Researchers are continually using chemical methods to alter their structures to make them more effective in treating and preventing diseases. Researchers are also continuously developing derivative drugs with high efficacy and few adverse effects. This article summarizes and analyzes derivatives with significant biological activities reported in recent research obtained by structural modification. The modification sites have mainly focused on the phenolic hydroxy groups, benzene rings, and diene bonds. Changes to the allyl bisphenol structure will result in unexpected benefits, including high activity, low toxicity, and good bioavailability. Furthermore, alongside earlier experimental research in our laboratory, the structure-activity relationships of magnolol and honokiol were preliminarily summarized, providing experimental evidence for improving their development and utilization.     

抗病原真菌药物的研究进展

本文概述了抗病原真菌药物的作用机制、研究现状和发展趋势。同时,结合本课题组的研究结果,对从甾体皂苷中寻找新型抗菌药物提出展望。     

Biotransformation and Dissolution of Petroleum Hydrocarbons in Natural Flowing Seawater at Low Temperature

The objective of this study was to establish methods for controlled studies of hydrocarbon depletion from thin oil films in cold natural seawater, and to determine biotransformation in relation to other essential depletion processes. Mineral oil was immobilized on the surface of hydrophobic Fluortex fabrics and used for studies of microbial biodegradation in an experimental seawater flow-through system at low temperatures (5.9-7.4 degrees C) during a test period of 42 days. The seawater was collected from a depth of 90 m, and microbial characterization by epifluorescence microscopy, fluorescence in situ hybridization, and most-probable number analysis showed relatively larger fractions of archaea and oil-degrading microbes than in the corresponding surface water. Chemical analysis of hydrocarbons attached to the fabrics during the test period showed that n-alkanes (C10-C36) were decreased by 98% after 21 days, while naphthalenes were depleted by 99-100% during the same period. At the end of the period 4-5 ring polyaromatic hydrocarbon (PAH) compounds were removed by 82% from the fabrics. Analysis of the recalcitrant pentacyclic triterpane C30 17alpha(H),21beta(H)-hopane showed that the oil remained adsorbed to the fabrics during the test period. Comparison of depletion analysis with calculation of hydrocarbon dissolution in a flow-through system indicated that naphthalenes and smaller PAH compounds (alkylated 2-ring and 3-ring compounds) were removed from the fabrics by dissolution. The data further implied that depletion of n-alkanes and 4-5 ring PAH hydrocarbons were the result of biotransformation processes. PCR amplification of bacterial 16S rRNA genes from microbes adhering on the immobilized oil surfaces showed the dominance of a few bands when analysed in denaturing gradient gel electrophoresis (DGGE). Sequence analysis of DGGE bands revealed phylogenetic affiliation to the alpha- and gamma-subdivisions of proteobacteria and to the Chloroflexus-Flavobacterium-Bacteroides group.