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.     

小单胞菌属次级代谢产物及其生物活性研究进展

小单胞菌属(Micromonospora)为稀有放线菌,广泛分布在土壤、海洋和动植物中,其所产代谢产物不仅具有抗菌、抗肿瘤、抗HIV等多种生物活性,而且化学结构新颖多样。本文从化学结构分类、生物活性等方面对近几年已报道的小单胞菌属来源的重要天然产物做了简要综述,以期为小单胞菌天然产物的开发和应用奠定基础。     

The endophytic Aspergillus strains: A bountiful source of natural products

Fungi that invade plant inner tissues without inducing disease symptoms are known as fungal endophytes. They represent a promising and tremendous reservoir of natural products with valuable biological potentials for application in medicine, agriculture and industry. Among the numerous existing endophytic fungi, Aspergillus strains constitute one of the most prolific sources of secondary metabolites with diverse chemical classes and interesting biological activities. This review covers the literature of the year 2020, reporting the isolation of 202 compounds obtained from more than 10 different endophytic Aspergillus species associated with different host plants. Analysis and interpretation of the collected data revealed that chemical investigation of endophytes belonging to the genus Aspergillus may greatly contribute to the discovery of potential drug leads. The isolated metabolites were chemically various and exhibited diverse biological activities such as antibacterial, anti-cancer, anti-plasmodial, anti-inflammatory, antioxidant, immunosuppressive and antifungal activities. Moreover, adoption of advanced technology in molecular biology together with modern chemical tools is anticipated to improve the discovery of new biopharmaceuticals from this valuable microbial world in the future.     

C7N氨基环醇家族的天然α-糖苷酶/淀粉酶抑制剂研究进展

C7N氨基环醇家族化合物是一类由放线菌产生的天然化合物,化学结构相对较新颖。其核心基团井岗胺赋予该家族化合物多种生物活性,其中最主要的是α-糖苷酶/淀粉酶抑制剂活性。该家族化合物在生物医学和农业领域中具有较大的应用价值。本文将结合作者的研究方向,综述已被报道的C7N家族α-糖苷酶/淀粉酶抑制剂的化学结构与生物活性。     

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。     

戊二酰亚胺类天然产物生物合成研究进展

微生物天然产物是天然药物的重要组成部分,而天然产物的良好生物活性很大程度上取决于发挥药效的结构基团。这些特殊药效基团的生物合成,通常是利用小分子羧酸、氨基酸等结构简单的初级代谢产物,经过复杂的生物化学过程,最终合成结构复杂活性多样的天然产物。戊二酰亚胺类天然产物是一类重要的细菌来源天然产物,它们具有良好的生物活性,是潜在的先导化合物,部分化合物已被开发成分子探针。本文综述了近年来微生物来源的戊二酰亚胺类天然产物及其生物合成研究,包括Iso-Migrastatin、Lactimidomyin、Cycloheximide、Streptimidone、Gladiostatin、Sesbanimide等,对戊二酰亚胺类天然产物的生物合成研究,将有效促进通过基因组挖掘策略寻找新型戊二酰亚胺类天然产物。     

Saccharopolyspora: an underexplored source for bioactive natural products

Actinomycetes are a rich source for secondary metabolites with a diverse array of biological activities. Among the various genera of actinomycetes, the genus Saccharopolyspora has long been recognized as a potential source for antibiotics and other therapeutic leads that belong to diverse classes of natural products. Members of the genus Saccharopolyspora have been widely reported from several natural sources including both terrestrial and marine environments. A plethora of this genus has been chemically investigated for the production of novel natural products with interesting pharmacological effects. Therefore, Saccharopolyspora is considered one of the pharmaceutical important genera that could provide further chemical diversity with potential lead compounds. In this review, the literature from 1976 until December 2018 was covered, providing a comprehensive survey of all natural products derived from this genus and their semi-synthetic derivatives along with their biological activities, whenever applicable. Moreover, the biological diversity of Saccharopolyspora species and their habitats were also discussed.     

芥子油苷在植物-生物环境关系中的作用

芥子油苷是一类含氮、含硫的植物次生代谢物质,主要分布于白花菜目的十字花科植物。芥子油苷及其降解产物具有多种生化活性,近年来人们更多地关注芥子油苷代谢与其它物质代谢途径的相互联系以及与植物生存环境的相互作用。介绍了芥子油苷及其分布、芥子油苷-黑芥子酶系统以及由芥子油苷介导的植物对昆虫、病原体的防御作用和植物与植物之间的化感作用的研究概况。     

Modern synthetic efforts toward biologically active terpenes

Terpenes represent one of the largest and most diverse classes of secondary metabolites, with over 55,000 members isolated to date. The terpene cyclase enzymes used in nature convert simple, linear hydrocarbon phosphates into an exotic array of chiral, carbocyclic skeletons. Further oxidation and rearrangement results in an almost endless number of conceivable structures. The enormous structural diversity presented by this class of natural products ensures a broad range of biological properties-ranging from anti-cancer and anti-malarial activities to tumor promotion and ion-channel binding. The marked structural differences of terpenes also largely thwart the development of any truly general strategies for their synthetic construction. This review focuses on synthetic strategies directed toward some of the most complex, biologically relevant terpenes prepared by total synthesis within the past decade. Of crucial importance are both the obstacles that modern synthetic chemists must confront when trying to construct such natural products and the key chemical transformations and strategies that have been developed to meet these challenges.     

Biological activities and potential cosmeceutical applications of bioactive components from brown seaweeds: a review

Seaweeds are the primary producers of all aquatic ecosystems. Chemical constituents isolated from diverse classes of seaweeds exert a wide range of nutritional, functional and biological activities. Unique metabolites of seaweeds possess specific biological properties that make them potential ingredients of many industrial applications such as functional foods, pharmaceuticals and cosmeceuticals. Cosmeceuticals of natural origin are becoming more popular than synthetic cosmetics. Hence, the investigation of new seaweeds derived functional components, a different source of natural products, has proven to be a promising area of cosmeceutical studies. Brown seaweeds also produce a range of active components including unique secondary metabolites such as phlorotannins and many of which have specific biological activities that give possibilities for their economic utilization. Brown seaweeds derived active compounds have been shown various functional properties including, antioxidant, antiwrinkling, whitening, antiinflammatory and antiallergy. It is well-known that these kind of biological effects are closely associated with cosmeceutical preparations. This communication reviews the current knowledge on brown seaweeds derived metabolites with various biological activities and the potential use as cosmeceutical ingredients. It is hoped that the reviewed literature on multifunctional properties of brown seaweeds will improve access to the seaweed based natural products specially the ability to incorporate these functional properties in cosmeceutical applications.     

Chemistry and biological activity of azoprenylated secondary metabolites

N-Prenyl secondary metabolites (isopentenylazo-, geranylazo-, farnesylazo- and their biosynthetic derivatives) represent a family of extremely rare natural products. Only in recent years have these alkaloids been recognized as interesting and valuable biologically active secondary metabolites. To date about 35 alkaloids have been isolated from plants mainly belonging to the Rutaceae family, and from fungi, bacteria, and/or obtained by chemical synthesis. These metabolites comprise anthranilic acid derivatives, diazepinones, and indole, and xanthine alkaloids. Many of the isolated prenylazo secondary metabolites and their semisynthetic derivatives are shown to exert valuable in vitro and in vivo anti-cancer, anti-inflammatory, anti-bacterial, anti-viral, and anti-fungal effects. The aim of this comprehensive review is to examine the different types of prenylazo natural products from a chemical, phytochemical and biological perspective.     

Microalgae in the postgenomic era: a blooming reservoir for new natural products

Bacteria, fungi, algae and higher plants are the most prolific producers of natural products (secondary metabolites). Compared to macroalgae, considerably fewer natural products have been isolated from microalgae, which offer the possibility of obtaining sufficient and well-defined biological material from laboratory cultures. Interest in microalgae is reinforced by large-scale data sets from genome sequencing projects and the development of genetic tools such as transformation protocols. This review highlights what is currently known about the biosynthesis and biological role of natural products in microalgae, with examples from isoprenoids, complex polyketides, nonribosomal peptides, polyunsaturated fatty acids and oxylipins, alkaloids, and aromatic secondary metabolites. In addition, we introduce a bioinformatic analysis of available genome sequences from totally 16 microalgae, belonging to the green and red algae, heterokonts and haptophytes. The results suggest that the biosynthetic potential of microalgae is underestimated and many microalgal natural products remain to be discovered.     

Chemical defensive substances of soft corals and gorgonians

Despite lack of efficient physical protection in the highly competitive and hostile environment, the marine invertebrates including soft corals and gorgonians can survive, mainly relying on their chemical defensive system by a series of secondary metabolites accumulating in their bodies or releasing to their surroundings. The chemical defensive functions of these secondary metabolites were found to serve as antipredatory, antimicrobial, allelopathy and antifouling agents. Study on chemical defensive substances from corals and gorgonians is one of the most important topics in marine chemical ecology. The research results could help us to understand the chemical ecological relationships between corals and their surrounding organisms. The research strategy and methodology played an enlightening role in the discovery of bioactive natural products and the generation of new drug lead compounds from marine sources. The chemical defensive substances from soft corals and gorgonians were reviewed. This review focused on the structures of these secondary metabolites as well as their functions including antipredatory, allelopathy and antifouling activities.     

Chemical defensive substances of soft corals and gorgonians

Despite lack of efficient physical protection in the highly competitive and hostile environment, the marine invertebrates including soft corals and gorgonians can survive, mainly relying on their chemical defensive system by a series of secondary metabolites accumulating in their bodies or releasing to their surroundings. The chemical defensive functions of these secondary metabolites were found to serve as antipredatory, antimicrobial, allelopathy and antifouling agents. Study on chemical defensive substances from corals and gorgonians is one of the most important topics in marine chemical ecology. The research results could help us to understand the chemical ecological relationships between corals and their surrounding organisms. The research strategy and methodology played an enlightening role in the discovery of bioactive natural products and the generation of new drug lead compounds from marine sources. The chemical defensive substances from soft corals and gorgonians were reviewed. This review focused on the structures of these secondary metabolites as well as their functions including antipredatory, allelopathy and antifouling activities.     

Secondary metabolites of slime molds (myxomycetes)

The compounds reported from the slime molds (myxomycetes) species are described. Almost 100 natural compounds including their chemical structures and biological activities are described in this review article. Only metabolites with a well-defined structure are included.     

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.     

软珊瑚(Sinularia flexibilis)和柳珊瑚(Plexaura homomalla)化学防御物质研究进展

软珊瑚(Sinularia flexibilis)和柳珊瑚(Plexaura homomalla)属于海洋低等无脊椎动物,虽然这些动物自身缺乏有效的物理防御手段,却能在竞争激烈的海洋环境中生存与繁衍,这主要是依靠其次级代谢产物的化学防御作用.这些次级代谢产物聚积在体内或释放到环境中,作用主要体现在抵御捕食者、抗病原微生物、克生与防附着等方面.珊瑚化学防御物质的研究有助于探讨珊瑚与其环境中其它生物的化学生态关系,属于海洋化学生态学研究的重要内容之一,其研究方法和思路对海洋活性天然产物乃至海洋新药先导化合物的发现,具有重要的启迪作用.综述了软珊瑚和柳珊瑚化学防御物质的研究进展,并阐释了软珊瑚和柳珊瑚中具有拒捕食、克生、防生物附着等生物活性的次级代谢产物的结构及其化学防御作用.     

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。     

Construction of a microbial natural product library for chemical biology studies

The RIKEN Natural Products Depository (NPDepo) is a public depository of small molecules. Currently, the NPDepo chemical library contains 39,200 pure compounds, half of which are natural products and their derivatives. In order to reinforce the uniqueness of our chemical library, we have improved our strategies for the collection of microbial natural products. Firstly, a microbial metabolite fraction library coupled with an MP (microbial products) plot database provides a powerful resource for the efficient isolation of microbial metabolites. Secondly, biosynthetic studies of microbial metabolites have enabled us to not only access ingenious biosynthetic machineries, but also obtain a variety of biosynthetic intermediates. Our chemical library contributes to the discovery of molecular probes for increasing our understanding of complex biological processes and for eventually developing new drug leads.