青霉属真菌次级代谢产物的结构类型及其药用活性的研究进展

青霉属(Penicillium)真菌属于腐生类真菌,是自然界中一类重要的分解者。其可以产生多种多样的次级代谢产物。这些结构新颖、功能特殊的次级代谢产物在抗菌、抗氧化、抗肿瘤等药物开发中发挥重要作用,主要由聚酮类、生物碱、萜类、大环内酯等化学结构类型组成。本文综述了青霉属真菌次级代谢产物的结构类型以及丰富的生物药用活性,该内容可为后续青霉属真菌新型天然药物的开发提供研究思路。     

海洋微生物源活性产物的发酵条件优化研究进展

海洋微生物因其独特的生境和代谢途径,能够产生结构新颖且具有抗肿瘤、抗菌、抗病毒和免疫调节等多种生物活性的代谢产物,从而成为新活性化合物的重要源泉,并在新药物开发领域中越来越受到重视。但微生物来源的活性产物产量普遍较低,需要通过发酵优化提高其产量,为后续深入研究和开发提供物质基础。因此,本文根据化学分类介绍了来源于海洋微生物的活性化合物及其发酵条件优化,以期为其他海洋微生物资源的挖掘与利用提供相应的参考。     

海洋曲霉属真菌抗菌活性物质的研究进展

海洋微生物由于其独特的生存环境造就了许多结构新颖、具有特殊生物活性的代谢产物。随着科学技术的发展,科学界掀起了对海洋微生物代谢物的研究浪潮。近年来的研究表明,海洋曲霉属真菌及其次级代谢产物具有抗肿瘤、抗菌、抗病毒等生物活性。通过查阅文献与资料,对近年来海洋曲霉属真菌及其次级代谢产物的化学结构及生物活性研究与开发的进展进行综述总结,以期有助于后续研究及应用。     

嗜盐微生物的工业应用研究及进展

嗜盐微生物是一类生长于高盐环境的微生物,在新型生物化工产业及生物修复领域具有突出的应用潜力。本文简要介绍了嗜盐微生物的种类、生理特性,着重阐述了嗜盐微生物产生的活性物质在工业生产上的应用价值和开发前景,总结了近年来国内外在嗜盐微生物工业应用上的研究进展,对嗜盐微生物的应用研究做了概括。     

海洋动物来源微生物的共培养研究进展

近年来,由于一些新疾病的发生和细菌耐药性的出现,微生物来源次级代谢产物的筛选重复率越来越高,微生物一些代谢基因在现有实验室条件下无法表达,所以需要发现新的微生物资源,同时找到激活微生物代谢产物基因的方法。海洋动物体内蕴含着大量的共附生微生物资源,可以产生很多具有生物活性的化合物,是潜在的药用资源。本文综述了近年来海洋动物(海鞘、海绵、珊瑚和海葵等)来源的微生物进行共培养的研究策略,包括共培养菌株的选择、共培养条件、群体感应和信号分子对共培养菌株的影响,以及不同种类微生物间的共培养实例。共培养与单培养相比,增加了次级代谢产物的种类,提高了次级代谢产物的生物活性或产量。共培养的研究有助于发现新的海洋动物来源微生物的活性天然产物,为海洋药物的开发提供新思路。     

极端嗜热微生物及其高温适应机制的研究进展

极端嗜热微生物在高温条件下生长繁殖,其必然具有适应高温环境的特殊细胞结构、基因类型以及生理生化机制。极端嗜热微生物的研究对探索生命的起源以及极端嗜热微生物的开发和应用具有重要意义。对极端嗜热微生物中细胞膜、核酸分子、蛋白质分子、代谢产物和辅酶的高温适应机制的研究进展进行了概述,旨为极端嗜热微生物以及来源于极端嗜热微生物的各种生物分子的开发和应用提供理论依据。     

源于海洋真菌的抗肿瘤天然产物

海洋真菌因其特殊的生存环境和代谢机制而具有产生新型生物活性物质的潜力。近年来随着对海洋微生物研究的深入,从海洋真菌中发现了越来越多的具有抗肿瘤活性且结构新颖的天然产物。这些海洋真菌有的分离自海水、海泥或海洋沉积物,有的来自于海洋生物体。本文综述了近几年来从海洋真菌中分离得到的抗肿瘤天然产物的研究状况。     

植物内生菌活性代谢产物最新研究进展

内生菌广泛存在于植物组织中,作为一种新型的微生物资源,具有丰富的物种多样性,也是发掘新型天然活性物质的重要途径之一,有些内生菌还能产生与宿主植物相同或相似的活性成分。因此从植物内生菌中挖掘抗菌尤其抗临床耐药菌、抗肿瘤等天然活性产物不仅为新药的研发提供了新的方向,还能在一定程度上解决传统的天然产物药源——药用植物生长缓慢、资源紧缺等问题。从多个角度概述了近年来国内外报道的植物内生菌次生代谢产物及其来源、生物活性等方面的主要成果和最新进展,以期为植物内生菌活性代谢产物的研究提供参考。     

新的生命形式──极端微生物

近年来,在许多以前被认为是生命禁区的区域,发现了各式各样的新的生命形式。它们生存繁衍的理想场所恰恰是一些极端环境,如嗜热菌、嗜冷菌、嗜酸菌、嗜碱菌、嗜盐菌、嗜压菌等,这些统称为极端微生物（ｅｘｔｒｅｍｏｐｈｉｌｅｓ）。极端微生物具有独特的基因类型,特殊的生理机制及特殊的代谢产物,作为地球上的边缘生命现象,极端微生物颇为耐人寻味。它在生命起源、系统进化等方面将给人们许多重要的启示,在生命行为的原理上也将拓展人们的概念。极端微生物存在的原理,又具有极大的应用价值,极端微生物的特殊机制及特殊产物,将使…     

植物内生放线菌多样性及其活性代谢产物的研究进展

植物内生放线菌是一类能与宿主植物长期协同生长且不引起植物感染的特殊微生物。其作为植物内生微生物资源的重要组成部分,不仅分布广泛,资源丰富,绝大部分可产生与宿主植物相同或相似的次生代谢产物,而且这些次级代谢产物往往丰富多样并具有多种生物活性,是寻找和开发新型先导化合物的重要资源,具有重要的研究意义和潜在的应用价值。植物内生放线菌作为一种亟待开发的重要微生物资源,其重要性越来越被研究人员所认同。就近年来国内外关于植物内生放线菌多样性和其次级代谢物抗菌、抗肿瘤、抗氧化和抗虫等生物活性的研究近况进行综述,以期为植物内生放线菌资源的深入研究和应用提供参考。     

相容溶质四氢嘧啶的微生物合成研究进展北大核心CSCD

四氢嘧啶(ectoine)作为一种氨基酸的衍生物,是嗜盐微生物胞内重要的天然次级代谢物,具有保护细胞和稳定生物大分子的功能,可广泛应用于药物制备佐剂、器官移植与保存、皮肤创伤修复与新型化妆品研发等生物医学领域。由于四氢嘧啶的医用价值和商业市场需求,文中从野生菌株的筛选与诱变育种、构建基因工程菌株与系统代谢整合工程菌株、四氢嘧啶的优化发酵与生产工艺以及抽提纯化工艺等方面,系统论述了四氢嘧啶高效积聚和过量化生产研究策略,并展望多组学、计算生物学及“细胞工厂”等技术在后续四氢嘧啶高效生产上的应用前景。     

嗜盐耐盐微生物抗盐胁迫相关离子转运蛋白研究进展

离子转运蛋白在维持细胞内pH稳态、离子动态平衡等方面发挥着重要作用。钠离子转运体和钾离子转运体在嗜盐耐盐微生物中广泛存在,其"保钾排钠"机制是微生物抗盐胁迫的两大策略之一。近年来,嗜盐耐盐微生物中许多新型钠、钾离子转运体被陆续发现,如RDD蛋白、UPF0118蛋白、DUF蛋白和KimA蛋白等;Fe³⁺、Mg²⁺等其他金属离子的转运蛋白也被证实可通过影响微生物胞内相容性溶质的合成起到渗透调节的作用。本文综述了嗜盐耐盐微生物中抗盐胁迫相关的各类离子转运蛋白,分析其分子结构和工作机理,并对这些蛋白在农业方面的应用进行了展望。继续发现新的离子转运蛋白,探究抗盐胁迫相关离子转运蛋白的结构和机理,解析各转运系统的协同作用及分子调控机制,将进一步加深对嗜盐耐盐微生物抗盐胁迫调控的认识,并为盐碱地农作物的改良等提供新的思路。     

安徽定远盐矿可培养嗜盐微生物多样性

【背景】嗜盐微生物多生活于高盐环境,具有独特的生理代谢特征,是一类重要的极端环境微生物资源。【目的】为更好地认识我国陆相盐矿的嗜盐微生物多样性组成,更好地开发利用嗜盐微生物资源积累丰富的微生物菌种。【方法】对安徽定远盐矿盐芯样品进行嗜盐微生物的纯培养分离,并对所分离菌株进行基于16SrRNA基因的测序和序列相似性分析,并对所分离菌株进行物种多样性分析。在此基础上,对代表菌株进行菌落形态和耐盐度及酶活测定。【结果】通过纯培养共分离获得了嗜盐微生物264株,其中嗜盐古菌150株,占56.8%;嗜盐细菌114株,占43.2%。嗜盐古菌物种分别来自于Halorubrum、 Halopenitus、 Haloterrigena、 Natrinema、 Natronoarchaeum和Natronomonas等6个属;嗜盐细菌物种分别来自于Pseudomonas、Aliifodinibius、Halobacillus、Halomonas和Halospina等5个属。通过代表菌株的酶活平板检测,发现产胞外蛋白酶菌株1株,酯酶1株,淀粉酶2株;能液化明胶菌株2株。在物种多样性组成方面,发现嗜盐古菌的物种多样性指数高于嗜盐细菌。【结论】本研究对我国安徽定远陆相盐矿的可培养嗜盐微生物多样性进行探究,积累了丰富的嗜盐微生物菌株资源。     

Microbiological transformation of mycophenolic acid

In our microbial screening program, we have isolated a fungal strain which produced mycophenolic acid (MPA). This compound is a selective inhibitor of guanine synthesis and, therefore, it has antibacterial, antiviral, antitumor and selective immunosuppressive activities, too. This last effect was utilised by Roche-Syntex to develop a derivative of MPA to the immunosuppressive drug CellCept®.

In order to obtain novel derivatives of MPA with an enhanced activity, we applied bioconversion of MPA with various microorganisms. TLC with densitometric evaluation and HPLC methods were developed for measurement of MPA derivatives. In the course of the bioconversion of MPA by using various types of microorganisms amidation of the carboxyl group, hydroxylation of the C₄-methyl group and formation of glycoside derivatives from the hydroxyl group located on C₇ were observed as the most frequently occurring transformations. The structures of bioconversion products were determined by UV, IR, ¹H NMR, ¹³C NMR and mass spectroscopic methods.

The taxonomic features of cultures of the species applied in the bioconversion were also determined.     

综述——纳米材料与药物输递：基于聚合物的环境敏感型纳米抗肿瘤药物传输系统的研究

环境敏感型聚合物纳米抗肿瘤药物传递系统能够响应外界环境的微小刺激,引起自身结构的变化,释放出药物,在肿瘤治疗方面具长效低毒、可控及高载药量等优势,已被广泛应用于生物医学领域．本文介绍了聚合物环境响应型纳米药物传输系统的发展近况,并从pH 值敏感型、温度敏感型、氧化还原敏感型、酶敏感型以及其他敏感型给药系统角度,阐述了环境敏感型药物传输系统在抗肿瘤领域的研究现状及未来展望．     

Culturable halophilic archaeal diversity of Ayakekumu salt lake located in Xinjiang, China

Molecular diversity of halophilic archaea from Ayakekumu salt lake was investigated by the polymerase chain reaction (PCR) amplification and culture methods. 19 water samples and 15 soil samples were taken from 19 sites within Ayakekumu salt lake in winter and spring. Under aerobic culture conditions, some halophilic microorganisms were isolated by five different media. The 16S rRNA gene sequences of 62 red strains were amplified by using PCR, determined by the DNA sequencer and analyzed through the BLASTn program subsequently. Results revealed that all sequences belonged to six genera grouped within the Halobacteriaceae. Mostly 16S rRNA gene sequences related to the genera Halorubrum (47%) and Natrinema (24%) were detected. Subsequent analysis by using Shannon index indicated that cultured halophilic archaeal diversities are not significantly different between winter and spring samplings in Ayakekumu salt lake. Similarity values of haloarchaeal 16S rRNA gene sequences to known sequences were less than 97%, suggesting the presence of two novel taxa. In addition, taxonomic characteristics of Natrinema altunense and Halobiforma lacisalsi isolated from Ayakekumu salt lake had been described previously. The discovery of the novel species provides new opportunity to further examine the diversity of these halophilic microorganisms in Ayakekumu salt lake.     

Culturable halophilic archaeal diversity of Ayakekumu salt lake located in Xinjiang, China

Molecular diversity of halophilic archaea from Ayakekumu salt lake was investigated by the polymerase chain reaction (PCR) amplification and culture methods. 19 water samples and 15 soil samples were taken from 19 sites within Ayakekumu salt lake in winter and spring. Under aerobic culture conditions, some halophilic microorganisms were isolated by five different media. The 16S rRNA gene sequences of 62 red strains were amplified by using PCR, determined by the DNA sequencer and analyzed through the BLASTn program subsequently. Results revealed that all sequences belonged to six genera grouped within the Halobacteriaceae. Mostly 16S rRNA gene sequences related to the genera Halorubrum (47%) and Natrinema (24%) were detected. Subsequent analysis by using Shannon index indicated that cultured halophilic archaeal diversities are not significantly different between winter and spring samplings in Ayakekumu salt lake. Similarity values of haloarchaeal 16S rRNA gene sequences to known sequences were less than 97%, suggesting the presence of two novel taxa. In addition, taxonomic characteristics of Natrinema altunense and Halobiforma lacisalsi isolated from Ayakekumu salt lake had been described previously. The discovery of the novel species provides new opportunity to further examine the diversity of these halophilic microorganisms in Ayakekumu salt lake.     

Metabolism of chloride in halophilic prokaryotes

While much understanding has been achieved on the intracellular sodium and potassium concentrations of halophilic and halotolerant microorganisms and on their regulation, we know little on the metabolism of anions. Archaea of the family Halobacteriaceae contain molar concentrations of chloride, which is pumped into the cells by cotransport with sodium ions and/or using the light-driven primary chloride pump halorhodopsin. Most halophilic and halotolerant representatives of the bacterial domain contain low intracellular ion concentrations, with organic osmotic solutes providing osmotic balance. However, some species show a specific requirement for chloride. In Halobacillus halophilus certain functions, such as growth, endospore germination, motility and flagellar synthesis, and glycine betaine transport are chloride dependent. In this organism the expression of a large number of proteins is chloride regulated. Other moderately halophilic Bacteria such as Halomonas elongata do not show a specific demand for chloride. A very high requirement for chloride was demonstrated in two groups of Bacteria that accumulate inorganic salts intracellularly rather than using organic osmotic solutes: the anaerobic Halanaerobiales and the aerobic extremely halophilic Salinibacter ruber. It is thus becoming increasingly clear that chloride has specific functions in haloadaptation in different groups of halophilic microorganisms.     

放线菌天然产物糖基化改造研究进展

放线菌可以产生结构多样的天然产物, 其中包括很多重要的抗菌和抗肿瘤药物。糖基化修饰在天然产物中广泛存在, 糖基侧链的变化往往会影响天然产物的生物活性。本文综述了放线菌来源天然产物糖基化改造的研究进展。糖基侧链改造的方法主要分为体内基因工程和体外酶学法。运用这两种方法已经成功对多种天然产物进行了糖基侧链改造, 获得了大量带有新糖基修饰的天然产物, 其中有些生物活性得以提高。天然产物糖基侧链改造为新药开发提供了一个重要的途径。     

Haloarchaea: worth exploring for their biotechnological potential

Halophilic archaea are unique microorganisms adapted to survive under high salt conditions and biomolecules produced by them may possess unusual properties. Haloarchaeal metabolites are stable at high salt and temperature conditions that are useful for industrial applications. Proteins and enzymes of this group of archaea are functional under salt concentrations at which bacterial counterparts fail to be active. Such properties makes haloarchaeal enzymes suitable for salt-based applications and their use under dehydrating conditions. For example, bacteriorhodopsin or the purple membrane protein present in halophilic archaea has the most recognizable applications in photoelectric devices, artificial retinas, holograms etc. Haloarchaea are also useful for bioremediation of polluted hypersaline areas. Polyhydroxyalkanoates and exopolysccharides produced by these microorganisms are biodegradable and have the potential to replace commercial non-degradable plastics and polymers. Moreover, halophilic archaea have excellent potential to be used as drug delivery systems and for nanobiotechnology by virtue of their gas vesicles and S-layer glycoproteins. Despite of possible applications of halophilic archaea, laboratory-to-industrial transition of these potential candidates is yet to be established.