不同生境来源杂色曲霉次级代谢产物研究进展

杂色曲霉是曲霉属的常见种类，广泛分布于海洋、高等植物、红树林和节肢动物等生境中，近年研究表明杂色曲霉可产生生物碱、萜类、聚酮等结构多样的次级代谢产物，具有抗菌、抗肿瘤、抗氧化、抗病毒等活性。本文总结了2017—2022年间报道的37株杂色曲霉次级代谢产物结构及其生物活性的研究进展，涉及325个次级代谢产物，其中新化合物111个。本文揭示了杂色曲霉的次级代谢产物与生境的相关性，对从更多生境来源的杂色曲霉及其它微生物资源来挖掘新天然产物具有参考作用。     

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。     

小球腔菌属次级代谢产物的化学及其生物学活性研究进展

小球腔菌可引发油菜黑胫病等给农业造成严重的经济损失。该属真菌的次级代谢产物研究开始较早,化合物分离工作主要围绕黑胫病致病菌株,研究发现该属真菌的次级代谢产物十分丰富,许多化学结构新颖、具有显著生物活性的化合物均被发现。为使该属的真菌资源得到充分的开发与利用,本文对40多年来报道的小球腔菌属次级代谢产物的化学及其生物学活性进行了较为全面的综述。     

海洋真菌及其活性代谢产物研究进展

微生物生理活性物质对人类健康极其重要。近年来,海洋微生物研究逐步成为热点,而海洋真菌是海洋微生物的重要组成部分。当前,具有生物活性的海洋真菌代谢产物被广泛应用于食品和医药产业中,研究和开发海洋真菌的生物活性代谢产物具有重要的实际意义。     

海绵共附生真菌多样性及其次级代谢产物的研究进展

海绵由于其独特的生理结构、进食方式使其体内部聚集了大量的微生物,这些微生物产生了多种结构新颖的生物活性物质,因此海绵及其共附生微生物的研究成为了海洋药物研发的热点。就海绵中共附生真菌的分布情况,新技术的应用及其生物次级代谢产物的生物活性展开综述。     

深海来源真菌次级代谢产物研究进展

深海环境复杂多样,微生物为了适应这种极端环境往往会形成独特的代谢途径,进而产生一些具有某种生理活性的结构新颖的次级代谢产物。真菌作为深海环境中的重要微生物类群之一,因其次级代谢产物出新率高、生物活性显著,近年来成为海洋天然产物研究的焦点,倍受研究者关注。本文综述了2004-2017年间发表的217个深海(50 m)真菌来源的新颖次级代谢产物,其来源菌株广泛分布在真菌18个属,主要集中在Penicillium属(30%)、Aspergillus属(24%)、Spiromastix属(13%)和Acremonium属(7%);其结构类型包括聚酮类(99个)、生物碱类(54个)、萜类(50个)、肽类(11个)、其他类(3个);活性研究主要集中在细胞毒性、抗菌、抗病毒、抗污损等方面。     

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.     

地衣及其内生真菌活性次级代谢产物研究进展

地衣是一种独特的菌藻共生体,能够在荒漠、高山、冻土等恶劣环境生存,具有特殊的生理结构和独特的生存环境。地衣及其内生真菌能够产生结构新颖、活性广泛的次级代谢产物,研究地衣及其内生真菌次级代谢产物对新型药用资源开发以及利用等方面都具有重要的意义。本文关注了近年来地衣及其内生真菌的次级代谢产物相关研究,并对其生物活性方面的研究成果进行综述。     

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。     

甘草来源内生真菌多样性和抗菌活性研究

甘草作为使用广泛的根茎入药中药材,其自身复杂的微环境蕴藏了丰富的微生物资源,是未被充分发掘的新结构、新机制抗菌活性天然产物资源库。本文主要聚焦内蒙、甘肃和宁夏甘草中内生真菌,经过表观形态学特征分析,结合ITS-rDNA共获得134株真菌,其归属于16个属,显示出较好的真菌群落多样性,同时还发现青霉和曲霉属为各地甘草内生真菌的优势菌属。对所得内生真菌静置发酵后获得的代谢粗提物,利用纸片扩散法进行抗菌活性筛选与分析,发现其中35株真菌次级代谢产物具有广谱的抗菌活性。对比HPLC-UV指纹图谱分析结果,发现多个内生真菌的次级代谢产物中具有系列紫外吸收的天然产物。本研究表明,不同产地的甘草来源内生真菌群落具有丰富的多样性和良好的抗菌活性,预示着潜在的新颖抗菌天然产物研究价值。     

Marine natural product peptides with therapeutic potential: Chemistry,biosynthesis, and pharmacology

The oceans are a uniquely rich source of bioactive metabolites, of which sponges have been shown to be among the most prolific producers of diverse bioactive secondary metabolites with valuable therapeutic potential. Much attention has been focused on marine bioactive peptides due to their novel chemistry and diverse biological properties. As summarized in this review, marine peptides are known to exhibit various biological activities such as antiviral, anti-proliferative, antioxidant, anti-coagulant, anti-hypertensive, anti-cancer, antidiabetic, antiobesity, and calcium-binding activities. This review focuses on the chemistry and biology of peptides isolated from sponges, bacteria, cyanobacteria, fungi, ascidians, and other marine sources. The role of marine invertebrate microbiomes in natural products biosynthesis is discussed in this review along with the biosynthesis of modified peptides from different marine sources. The status of peptides in various phases of clinical trials is presented, as well as the development of modified peptides including optimization of PK and bioavailability.     

Achievements in the Study of Marine Low‐Molecular Weight Biologically Active Metabolites from the Vietnamese Territorial Waters as a Result of Expeditions aboard the Research Vessel ‘Akademik Oparin’ (2004–2017)

Until 2004, the secondary metabolites of marine organisms of the Vietnamese territorial waters had been studied very poorly. Only four new compounds were isolated from 1977 to 2003. Joint Russian‐Vietnamese expeditions aboard the research vessel ‘Akademik Oparin’ made it possible to study in detail the chemical diversity of marine micro‐ and macroorganisms. As a result of five expeditions, more than 250 low‐molecular weight natural compounds, including 117 new metabolites, were isolated from marine invertebrates and microfilamentous fungi. Their biological activities, such as cytotoxic, cytoprotective, and antioxidant activities, were investigated. Information about the structure and biological activity of the compounds, the source for their isolation and the geographical location of the objects is summarized in this review.     

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。     

Developing Aspergillus as a host for heterologous expression

Filamentous fungi have long been used for production of a range of valuable products; with the advent of molecular biology, it became apparent that these fungi possess considerable potential as expression hosts for the production of heterologous proteins and small molecules. Aspergillus is an important genus, including well known species of economically significant molds, and widely used for basic genetic research. The development of a genetic engineering "toolkit" for Aspergillus, such as those existing for the simpler yeasts and bacteria, was delayed due to the added complexity of the filamentous fungi, and also to the lesser resources devoted to their study. History of the development of Aspergillus as an expression host, current state of the art and future directions are reviewed, touching on related research in other fungi when discussing the areas of greatest potential for future biotechnological applications, focusing on the large and diverse families of fungal secondary metabolites.     

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.     

红树林内生真菌研究进展

红树林作为一种特殊的植物群落具有丰富的内生真菌资源,目前已分离鉴定的红树林真菌超过200种,成为海洋真菌的第二大类群,已报道的红树林内生真菌主要类群是链格孢霉(Alternaria)、曲霉(Aspergillus)、芽枝霉(Cladosporium)、炭疽菌(Colletotrichum)、镰孢霉(Fusarium)、拟青霉(Paecilomyces)、拟盘多毛孢(Pestalotiopsis)、青霉(Penicillium)、茎点霉(Phoma)、拟茎点霉(Phomopsis)、叶点霉(Phyllosticta)和木霉(Trichoderma)等.大部分红树林内生真菌具有较宽的宿主范围,极少数只有单一的宿主,不同红树林植物的内生真菌区系及优势种群有很大差异.红树林内生真菌的定殖因宿主植物不同部位、植株的年龄及季节和环境的变化明显不同.红树林内生真菌能产生多种代谢产物,具有抗菌、抗肿瘤等药用价值.红树林植物内生真菌的研究和开发具有重要意义.本文综述了红树林内生真菌的生物多样性及其分布、生物学功能和次生代谢产物等方面的研究进展.     

Natural products potential of Dictyoceratida sponges-associated micro-organisms

The marine environment represents one of the most underexplored environments in the world. Marine sponges have a higher taxonomic diversity according to definite environmental conditions. They have been considered interesting sources for bioactive compounds. Dictyoceratida sponges are divided into five families which are widely distributed and habituating different types of micro-organisms. However, some secondary metabolites are probably not produced by the sponges themselves, but rather by their associated micro-organisms. These secondary metabolites are characterized by different chemical structures and consequently different biological activities. This review outlines the reported secondary metabolites from micro-organisms associated with Dictyoceratida sponges and their investigated biological activities from 1991 to 2019. The increasing research studies in this field can play a major role in marine microbial natural products drug discovery in the future.     

Pharmaceutically active secondary metabolites of marine actinobacteria

Marine actinobacteria are one of the most efficient groups of secondary metabolite producers and are very important from an industrial point of view. Many representatives of the order Actinomycetales are prolific producers of thousands of biologically active secondary metabolites. Actinobacteria from terrestrial sources have been studied and screened since the 1950s, for many important antibiotics, anticancer, antitumor and immunosuppressive agents. However, frequent rediscovery of the same compounds from the terrestrial actinobacteria has made them less attractive for screening programs in the recent years. At the same time, actinobacteria isolated from the marine environment have currently received considerable attention due to the structural diversity and unique biological activities of their secondary metabolites. They are efficient producers of new secondary metabolites that show a range of biological activities including antibacterial, antifungal, anticancer, antitumor, cytotoxic, cytostatic, anti-inflammatory, anti-parasitic, anti-malaria, antiviral, antioxidant, anti-angiogenesis, etc. In this review, an evaluation is made on the current status of research on marine actinobacteria yielding pharmaceutically active secondary metabolites. Bioactive compounds from marine actinobacteria possess distinct chemical structures that may form the basis for synthesis of new drugs that could be used to combat resistant pathogens. With the increasing advancement in science and technology, there would be a greater demand for new bioactive compounds synthesized by actinobacteria from various marine sources in future.     

厦门杏林湾红树林根际真菌分离及活性分析

【背景】海洋微生物是天然药物资源宝库,海洋环境中的微生物能够产生很多区别于陆生微生物的天然产物。红树林生长于陆地与海洋交界带的滩涂浅滩,是陆地向海洋过渡的特殊生态系统,可能蕴含着丰富的微生物资源和潜在的大量结构新颖的代谢产物。【目的】以厦门杏林湾红树林根际海泥和海水为研究对象,探索其中可培养海洋真菌的多样性及其发酵提取物的抗细菌和抗真菌活性,以期为发现新的药物先导化合物提供菌株资源。【方法】样品预处理后涂布于GPY、PDA、Martin和MEA这4种培养基,28℃倒置培养,待培养基上长出合适大小的菌落后,挑取单菌落接种于PDA培养基纯化。利用纸片扩散法对发酵提取物进行抗菌活性筛选,通过高效液相色谱分析提取物的化学多样性,并采用形态观察结合rDNAITS序列分析对活性较好的4株真菌进行菌种鉴定。【结果】共分离出71株真菌,其中49株真菌对金黄色葡萄球菌有抗性,6株真菌对白色念珠菌有抗性,2株真菌对大肠杆菌有抗性,菌株HS5-MEA-4和HS6-MEA-10初步鉴定为土曲霉,菌株HS5-GPY-7和HS6-GPY-15分别为棘孢曲霉和Aspergillus templicola。【结论】初步认知了厦门杏林湾红树林环境真菌多样性及其发酵提取物的活性和化学多样性特征,为后续海洋真菌次级代谢产物研究提供了依据。     

杜比亚蟑螂共生真菌次生代谢产物及其生物活性

为探究杜比亚蟑螂体内共生真菌种类,测定共生真菌次生代谢产物的抑菌活性和抗氧化活性,筛选出具有抗菌和抗氧化活性的菌株,本研究采用组织块分离法分离杜比亚蟑螂体内的共生真菌,通过形态学和分子生物学相结合的方法对分离到的共生真菌进行鉴定;分别采用薄层层析-生物自显影法和DPPH法测定共生真菌次生代谢产物的抗细菌活性和抗氧化活性。结果表明,从杜比亚蟑螂体内共分离鉴定得到5种不同的共生真菌,主要分布于青霉属(1株)、曲霉属(3株)和聚孢霉属(1株)。活性测定的结果表明,菌株Bdf-2、Bdf-4和Bdf-5表现出较好的抗菌活性,且菌液提取物的抗菌活性要强于菌丝。Bdf-1,Bdf-2和Bdf-3菌液次生代谢产物表现出抗氧化活性,IC 50值分别为0.26 mg/mL、2.20 mg/mL和0.75 mg/mL。杜比亚蟑螂共生真菌以青霉属和曲霉属为主,且具有抗菌和抗氧化活性的次生代谢产物主要分布于菌液中。