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。     

源自海洋真菌的抗肿瘤活性天然产物研究新进展

近年来,海洋真菌因其能够产生大量结构新颖、活性显著的代谢产物而受到广泛关注,其中许多代谢产物具有较强的抗肿瘤活性。本文按照海洋真菌的来源进行分类,从海洋动物来源真菌、红树林来源真菌、海洋沉积物来源真菌、海藻来源真菌、海水来源真菌等5个方面,综述了2014~2016年4月以来发表的具有抗肿瘤活性的海洋真菌来源的新天然产物,主要介绍天然产物的化学结构和生物活性,为具有抗肿瘤活性的海洋真菌天然产物的进一步研究开发提供参考。     

海绵来源真菌天然产物的研究进展

随着海洋药物及其药物先导化合物研究的不断深入,海绵来源微生物,因其种类繁多、代谢产物复杂多样,引发了科研工作者的兴趣。许多化合结构新颖、具有强烈生物活性的化合物从海绵来源真菌中发现,包括多肽、生物碱、聚酮类、萜类等。本文仅就近几年来所报道的海绵来源真菌新天然产物的结构类型及其生物活性做简要介绍。     

海洋曲霉来源的新天然产物

海洋真菌由于其遗传背景复杂、代谢产物种类多且产量高,已成为海洋微生物新天然产物的主要来源,从我们对2010–2013年初的海洋微生物来源新天然产物的统计来看,研究最多的是曲霉属(Aspergillus)真菌,占海洋真菌来源新天然产物的31%。本文从菌株来源、化合物结构及其生物活性等方面,综述了自1992年第一个海洋曲霉天然产物到2014年8月已报道的共512个海洋曲霉来源的新天然产物。这些海洋天然产物具有丰富的化学多样性,且36%的化合物表现出细胞毒、抑菌、抗氧化和抗寄生虫等生物活性;含氮化合物是其主要的结构类型、约占曲霉源海洋天然产物总数的52%,也是出现活性化合物比例最高的结构类型、约40%的含氮化合物具有生物活性,其中脱氢二酮哌嗪生物碱halimide的化学衍生物plinabulin已结束II期临床研究,并于2015年第三季度开始在美国和中国进行III期临床研究,用于治疗转移性的晚期非小细胞肺癌。     

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。     

海洋真菌活性代谢产物最新研究进展

海洋微生物因其特殊的生存环境而具有产生新型生物活性物质的巨大潜力.近年来,从海洋真菌中分离鉴定了许多结构新颖的次级代谢产物,这些化合物显示了良好的抗肿瘤、抗细菌或抗真菌等生物活性.本文对近两年来海洋真菌所产生的活性物质的研究进展进行综述,并对其发展进行展望.     

真菌代谢产物的药物发现——资源、问题和策略

本期菌物学报“真菌生物活性代谢产物的药物发现专刊”刊登了7篇深度论述的综述性文章,19篇研究论文及2篇简报。内容涉及植物内生真菌产紫杉醇/紫杉烷的研究现状及最新进展、虫草菌素产生菌的培养策略及其药理学研究进展、灵芝三萜和胞外多糖生物合成的调控策略、淡水和海水真菌活性代谢产物研究进展等。本期内容还涉及内生真菌的分离和鉴定、海洋真菌的代谢产物分离、大型真菌的培养、代谢产物的分离及其药理学研究、酚类化合物测定方法、蛋白质组学以及生物转化等研究,基本体现了我国真菌代谢产物新药发现研究的最新进展,对真菌代谢产物合成调控、活性代谢产物分离和结构鉴定以及药理学研究等都具有重要的参考价值。     

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。     

微生物肽类次级代谢产物研究进展

微生物肽类次级代谢产物是一类重要的天然产物,因含有稀有氨基酸而具有丰富的化学结构和生物活性。随着微生物天然产物分离纯化技术的发展,新型肽类产物层出不穷,在微生物次级代谢产物的研究领域扮演了重要的角色。本文综述近年来发现的来自细菌和真菌的微生物肽类代谢产物,以及采用基因挖掘等手段人工合成的新型肽类产物,并结合近年来本团队昆虫病原线虫共生菌肽类产物的研究积累,分析微生物肽类产物研究存在的问题及可能的解决方案,以期为微生物导向的新型活性肽类产物的深入发掘和应用研究提供参考。     

海洋沉积环境来源真菌次生代谢产物的研究

海洋沉积环境复杂多样,微生物往往进化形成与其环境相适应的代谢系统.真菌作为海洋沉积环境中的重要微生物,它们的次生代谢产物结构出新率高、生物活性显著,是开发海洋先导药物的新兴资源.本文综述了1995-2011年间发表的200个海洋沉积环境真菌次生代谢产物,其来源菌株广泛分布在真菌16个属,主要集中在Penicillium属(30％)、Aspergillus属(19％)、Spicaria属(18％)和Trichoderma属(13％);其结构类型包括生物碱类(86个)、萜类(42个)、聚酮类(42个)、肽类(15个)、甾体类(5个)、脑苷脂类(4个)和其他类(6个),活性研究主要集中在细胞毒性和抗菌等方面.     

海洋真菌生物活性物质研究之管见

海洋真菌是活性海洋天然产物的重要来源,到目前为止,已从海洋真菌的发酵产物中分离鉴定了1,117个新化合物。介绍了海洋真菌次生代谢产物的研究历史、现状、特点、研究方法、存在问题及其在新药研究中的应用前景。     

Major bioactive metabolites from marine fungi: A Review

Biologists and chemists of the world have been attracted towards marine natural products for the last five decades. Approximately 16,000 marine natural products have been isolated from marine organisms which have been reported in approximately 6,800 publications, proving marine microorganisms to be a invaluable source for the production of novel antibiotic, anti tumor, and anti inflammatory agents. The marine fungi particularly those associated with marine alga, sponge, invertebrates, and sediments appear to be a rich source for secondary metabolites, possessing Antibiotic, antiviral, antifungal and antiyeast activities. Besides, a few growth stimulant properties which may be useful in studies on wound healing, carcinogenic properties, and in the study of cancers are reported. Recent investigations on marine filamentous fungi looking for biologically active secondary metabolites indicate the tremendous potential of them as a source of new medicines. The present study reviews about some important bioactive metabolites reported from marine fungal strains which are anti bacterial, anti tumour and anti inflammatory in action. It highlights the chemistry and biological activity of the major bioactive alkaloids, polyketides, terpenoids, isoprenoid and non-isoprenoid compounds, quinones, isolated from marine fungi.     

海洋真菌来源的抗菌活性物质研究：方法与进展

病原微生物的耐药性已严重威胁到人类的健康,因此,研发结构新颖、活性显著的新型抗生素已迫在眉睫。海洋独特的生态环境孕育了多样的微生物种群,为抗菌活性先导化合物的发现提供了丰富的资源。简要介绍了海洋真菌的特点及抗菌活性化合物的研究方法,并从海洋动物来源真菌、海藻来源真菌、海洋沉积物来源真菌和红树林植物来源真菌等4个方面,综述了从2000年至今已报道的海洋真菌抗菌活性次级代谢产物的研究进展,其中包括83个抗菌活性化合物,引用国内外文献54篇。     

Metabolites of marine organisms as regulators of O-glycosylhydrolases

The ability of metabolites contained in culture liquid of 62 strains of marine fungi to affect the activity of two digestive enzymes of marine mollusks--endo-1,3-beta-D-glucanase of Spisula sachalinensis and beta-D-glucosidase of Littorina kurila--was studied. It was found that 66 and 71% of specimens activated, 18 and 7% inhibited, and 16 and 22% did not affect the activity of endo-1,3-beta-D-glucanase and beta-D-glucosidase, respectively. It is demonstrated that the metabolites of brown algae and marine sponges can be used for a targeted regulation of enzyme biosynthesis by marine fungi. The protein inhibitor of endo-1,3-beta-D-glucanases isolated from the brown alga Laminaria cichorioides blocked the biosynthesis of almost all O-glycosylhydrolases in five strains of marine fungi studied. The presence in culture medium of halistanol sulfate from the marine sponge of the family Halichondriidae either did not affect or activated the biosynthesis of enzymes involved in carbohydrate metabolism by marine fungi.     

Marine microorganisms as biocontrol agents against fungal phytopathogens and mycotoxins

Mycotoxins are a serious food safety concern for human and animal health. Much attention should be paid to the dietary exposure to mycotoxins in order to minimise the risk of mycotoxin contamination in the food chain. Among the reported strategies to manage the mycotoxin contamination into food and feed, biological control seems a promising approach, depending on their biological origins, and on the use of living organisms or their derivatives. Marine microorganisms have developed unique metabolic and physiological capabilities to thrive in extreme habitats and produce novel metabolites which are not often present in microbes of terrestrial origin. Some marine bacteria and fungi have a good potential for the control of fungal phytopathogens and mycotoxins. Biologists and chemists are needed to work together to explore the storehouse of marine microorganisms and marine active metabolites, because marine bacteria and fungi have a huge potential for practical application in biocontrol of fungal phytopathogens and preventing mycotoxin contamination.     

Effect of sea water concentration on hyphal growth and antimicrobial metabolite production in marine fungi

We studied the effect of sea water concentration in a culture medium on fungal growth and the production of antimicrobial metabolites. Most of the marine fungal isolates were identified as members of the same genera as terrestrial isolates, such asAspergillus andTrichoderma. Many of the marine fungi isolated grew more abundantly as the sea water concentration increased. The production of antimicrobial materials was improved as the sea water concentration increased. Even though the marine fungi were considered to be similar to fungi from terrestrial environments, from a mycological perspective, the two types have different physiological characteristics. The fungi from marine samples are useful microbial resources in the search for new bioactive compounds.     

海洋石油降解微生物及其降解机理

微生物修复作为一种新型环保的生物修复技术,已成为海洋石油污染生物修复的核心技术。对海洋石油降解微生物的种类即细菌、蓝藻、真菌以及藻类进行了总结,对微生物对石油烃的降解途径与降解机理进行了综述。微生物降解烷烃的过程包括末端氧化、烷基氢过氧化物以及环己烷降解3种形式。微生物对芳香烃的降解是通过芳香烃被氧化酶氧化导致苯环开环来实现的。微生物对多环芳烃的降解是在单加氧酶或双加氧酶的催化作用下被最终降解为二氧化碳和水而被分解。并对影响石油烃降解微生物的因素包括温度、营养物质等因素进行了分析。     

Lapachol biotransformation by filamentous fungi yields bioactive quinone derivatives and lapachol-stimulated secondary metabolites

Abstract

Lapachol is a natural naphthoquinone with a range of biological effects, including anticancer activity. Microbial transformations of lapachol can lead to the formation of new biologically active compounds. In addition, fungi can produce secondary metabolites that are also important for drug discovery. The goal of this study was to evaluate the ability of filamentous fungi to biotransform lapachol into biologically active compounds and identify secondary metabolites produced in the presence of lapachol. Seven out of nine strains of filamentous fungi tested exhibited the ability to biotransform or biodegrade lapachol. The bioactive derivatives norlapachol and isolapachol were identified among biotransformation products. Moreover, lapachol stimulated the production of pyrrolo-[1,2-a] pyrazine-1,4-dione, hexahydro-3-(2-methylpropyl) and phenol-2,4-bis-(1,1-dimethylethyl), secondary metabolites already known to have antimicrobial and antioxidant activities. These results open the perspective of using these strains of filamentous fungi for lapachol biotransformation and efficient production of several biologically active compounds.     

Molecular profiling of marine endophytic fungi from green algae: Assessment of antibacterial and anticancer activities

Bioactive natural metabolites, especially from the marine endophytic fungi, are largely unexplored. Endophytic fungi are being increasingly recognized as a group of organisms that produce novel metabolites of industrial importance. This study investigated the anticancer and antibacterial potential of the marine algal endophyte, Penicillium chrysogenum. The different organic solvent extracts of the endophytic fungi grown on different growth medium were analyzed for anticancer and antibacterial activities. The highest inhibitory activity was observed for the ethyl acetate (EA) extract of the culture filtrate grown in potato dextrose broth (PDB) for 21 days, against the tested human breast cancer cell (MCF-7) line. Similarly, the PDB-EA extract showed an appreciable activity against the human pathogens. The biochemical analysis of the Cha EA metabolites revealed terpenoids, steroids, phenolics and flavones. Gas Chromatography (GCMS) data revealed several bioactive compounds such as anthraquinone and cinnamic acid. The Cha EA extract induced membrane damage and thus, apoptosis in MCF-7cells. The secondary metabolites produced by these marine endophytic fungi have contributed to considerable anticancer and antimicrobial activities and hence, this study is an evidence of potential sources of antimicrobial and anticancer compounds from Penicillium chrysogenum.