scholarly journals Natural Indole Alkaloids from Marine Fungi: Chemical Diversity and Biological Activities

2021 ◽  
Author(s):  
Jiao Li ◽  
Chun-Lin Zhuang

The indole scaffold is one of the most important heterocyclic ring systems for pharmaceutical development, and serves as an active moiety in several clinical drugs. Fungi derived from marine origin are more liable to produce novel indole-containing natural products due to their extreme living environments. The indole alkaloids from marine fungi have drawn considerable attention for their unique chemical structures and significant biological activities. This review attempts to provide a summary of the structural diversity of marine fungal indole alkaloids including prenylated indoles, diketopiperazine indoles, bisindoles or trisindoles, quinazoline-containing indoles, indole-diterpenoids, and other indoles, as well as their known biological activities, mainly focusing on cytotoxic, kinase inhibitory, antiinflammatory, antimicrobial, anti-insecticidal, and brine shrimp lethal effects. A total of 306 indole alkaloids from marine fungi have been summarized, covering the references published from 1995 to early 2021, expecting to be beneficial for drug discovery in the future.

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 488
Author(s):  
Afrah E. Mohammed ◽  
Zainab H. Abdul-Hameed ◽  
Modhi O. Alotaibi ◽  
Nahed O. Bawakid ◽  
Tariq R. Sobahi ◽  
...  

By the end of the twentieth century, the interest in natural compounds as probable sources of drugs has declined and was replaced by other strategies such as molecular target-based drug discovery. However, in the recent times, natural compounds regained their position as extremely important source drug leads. Indole-containing compounds are under clinical use which includes vinblastine and vincristine (anticancer), atevirdine (anti-HIV), yohimbine (erectile dysfunction), reserpine (antihypertension), ajmalicine (vascular disorders), ajmaline (anti-arrhythmic), vincamine (vasodilator), etc. Monoterpene Indole Alkaloids (MIAs) deserve the curiosity and attention of researchers due to their chemical diversity and biological activities. These compounds were considered as an impending source of drug-lead. In this review 444 compounds, were identified from six genera belonging to the family Apocynaceae, will be discussed. These genera (Alstonia, Rauvolfia, Kopsia, Ervatamia, and Tabernaemontana, and Rhazya) consist of 400 members and represent 20% of Apocynaceae species. Only 30 (7.5%) species were investigated, whereas the rest are promising to be investigated. Eleven bioactivities, including antibacterial, antifungal, anti-inflammatory and immunosuppressant activities, were reported. Whereas cytotoxic effect represents 47% of the reported activities. Convincingly, the genera selected in this review are a wealthy source for future anticancer drug lead.


Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3227
Author(s):  
Yuanwei Liu ◽  
Kishneth Palaniveloo ◽  
Siti Aisyah Alias ◽  
Jaya Seelan Sathiya Seelan

Soft corals are widely distributed across the globe, especially in the Indo-Pacific region, with Sarcophyton being one of the most abundant genera. To date, there have been 50 species of identified Sarcophyton. These soft corals host a diverse range of marine fungi, which produce chemically diverse, bioactive secondary metabolites as part of their symbiotic nature with the soft coral hosts. The most prolific groups of compounds are terpenoids and indole alkaloids. Annually, there are more bio-active compounds being isolated and characterised. Thus, the importance of the metabolite compilation is very much important for future reference. This paper compiles the diversity of Sarcophyton species and metabolites produced by their associated marine fungi, as well as the bioactivity of these identified compounds. A total of 88 metabolites of structural diversity are highlighted, indicating the huge potential these symbiotic relationships hold for future research.


Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1898
Author(s):  
Fauzia Izzati ◽  
Mega Ferdina Warsito ◽  
Asep Bayu ◽  
Anggia Prasetyoputri ◽  
Akhirta Atikana ◽  
...  

Marine invertebrates have been reported to be an excellent resource of many novel bioactive compounds. Studies reported that Indonesia has remarkable yet underexplored marine natural products, with a high chemical diversity and a broad spectrum of biological activities. This review discusses recent updates on the exploration of marine natural products from Indonesian marine invertebrates (i.e., sponges, tunicates, and soft corals) throughout 2007–2020. This paper summarizes the structural diversity and biological function of the bioactive compounds isolated from Indonesian marine invertebrates as antimicrobial, antifungal, anticancer, and antiviral, while also presenting the opportunity for further investigation of novel compounds derived from Indonesian marine invertebrates.


2020 ◽  
Vol 6 (4) ◽  
pp. 312
Author(s):  
Jia Chen ◽  
Zhimin Li ◽  
Yi Cheng ◽  
Chunsheng Gao ◽  
Litao Guo ◽  
...  

Sphinganine-analog mycotoxins (SAMs) including fumonisins and A. alternata f. sp. Lycopersici (AAL) toxins are a group of related mycotoxins produced by plant pathogenic fungi in the Fusarium genus and in Alternaria alternata f. sp. Lycopersici, respectively. SAMs have shown diverse cytotoxicity and phytotoxicity, causing adverse impacts on plants, animals, and humans, and are a destructive force to crop production worldwide. This review summarizes the structural diversity of SAMs and encapsulates the relationships between their structures and biological activities. The toxicity of SAMs on plants and animals is mainly attributed to their inhibitory activity against the ceramide biosynthesis enzyme, influencing the sphingolipid metabolism and causing programmed cell death. We also reviewed the detoxification methods against SAMs and how plants develop resistance to SAMs. Genetic and evolutionary analyses revealed that the FUM (fumonisins biosynthetic) gene cluster was responsible for fumonisin biosynthesis in Fusarium spp. Sequence comparisons among species within the genus Fusarium suggested that mutations and multiple horizontal gene transfers involving the FUM gene cluster were responsible for the interspecific difference in fumonisin synthesis. We finish by describing methods for monitoring and quantifying SAMs in food and agricultural products.


Marine Drugs ◽  
2020 ◽  
Vol 18 (6) ◽  
pp. 321 ◽  
Author(s):  
Minghua Jiang ◽  
Zhenger Wu ◽  
Heng Guo ◽  
Lan Liu ◽  
Senhua Chen

Marine-derived fungi are a significant source of pharmacologically active metabolites with interesting structural properties, especially terpenoids with biological and chemical diversity. In the past five years, there has been a tremendous increase in the rate of new terpenoids from marine-derived fungi being discovered. In this updated review, we examine the chemical structures and bioactive properties of new terpenes from marine-derived fungi, and the biodiversity of these fungi from 2015 to 2019. A total of 140 research papers describing 471 new terpenoids of six groups (monoterpenes, sesquiterpenes, diterpenes, sesterterpenes, triterpenes, and meroterpenes) from 133 marine fungal strains belonging to 34 genera were included. Among them, sesquiterpenes, meroterpenes, and diterpenes comprise the largest proportions of terpenes, and the fungi genera of Penicillium, Aspergillus, and Trichoderma are the dominant producers of terpenoids. The majority of the marine-derived fungi are isolated from live marine matter: marine animals and aquatic plants (including mangrove plants and algae). Moreover, many terpenoids display various bioactivities, including cytotoxicity, antibacterial activity, lethal toxicity, anti-inflammatory activity, enzyme inhibitor activity, etc. In our opinion, the chemical diversity and biological activities of these novel terpenoids will provide medical and chemical researchers with a plenty variety of promising lead compounds for the development of marine drugs.


2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Fabien Le Chevalier ◽  
Isabelle Correia ◽  
Lucrèce Matheron ◽  
Morgan Babin ◽  
Mireille Moutiez ◽  
...  

Abstract Background Cyclodipeptide oxidases (CDOs) are enzymes involved in the biosynthesis of 2,5-diketopiperazines, a class of naturally occurring compounds with a large range of pharmaceutical activities. CDOs belong to cyclodipeptide synthase (CDPS)-dependent pathways, in which they play an early role in the chemical diversification of cyclodipeptides by introducing Cα-Cβ dehydrogenations. Although the activities of more than 100 CDPSs have been determined, the activities of only a few CDOs have been characterized. Furthermore, the assessment of the CDO activities on chemically-synthesized cyclodipeptides has shown these enzymes to be relatively promiscuous, making them interesting tools for cyclodipeptide chemical diversification. The purpose of this study is to provide the first completely microbial toolkit for the efficient bioproduction of a variety of dehydrogenated 2,5-diketopiperazines. Results We mined genomes for CDOs encoded in biosynthetic gene clusters of CDPS-dependent pathways and selected several for characterization. We co-expressed each with their associated CDPS in the pathway using Escherichia coli as a chassis and showed that the cyclodipeptides and the dehydrogenated derivatives were produced in the culture supernatants. We determined the biological activities of the six novel CDOs by solving the chemical structures of the biologically produced dehydrogenated cyclodipeptides. Then, we assessed the six novel CDOs plus two previously characterized CDOs in combinatorial engineering experiments in E. coli. We co-expressed each of the eight CDOs with each of 18 CDPSs selected for the diversity of cyclodipeptides they synthesize. We detected more than 50 dehydrogenated cyclodipeptides and determined the best CDPS/CDO combinations to optimize the production of 23. Conclusions Our study establishes the usefulness of CDPS and CDO for the bioproduction of dehydrogenated cyclodipeptides. It constitutes the first step toward the bioproduction of more complex and diverse 2,5-diketopiperazines.


Author(s):  
Sanrda Kim Tiam ◽  
Muriel Gugger ◽  
Justine Demay ◽  
Severine Le Manach ◽  
Charlotte Duval ◽  
...  

Cyanobacteria are an ancient lineage of slow-growing photosynthetic bacteria and a prolific source of natural products with diverse chemical structures and potent biological activities and toxicities. The chemical identification of these compounds remains a major bottleneck. Strategies that can prioritize the most prolific strains and novel compounds are of great interest. Here, we combine chemical analysis and genomics to investigate the chemodiversity of secondary metabolites based on their pattern of distribution within some cyanobacteria. Planktothrix being a cyanobacterial genus known to form blooms worldwide and to produce a broad spectrum of toxins and other bioactive compounds, we applied this combined approach on four closely related strains of Planktothrix. The chemical diversity of the metabolites produced by the four strains was evaluated using an untargeted metabolomics strategy with high-resolution LC-MS. Metabolite profiles were correlated with the potential of metabolite production identified by genomics for the different strains. Although, the Planktothrix strains present a global similarity in term biosynthetic cluster gene for microcystin, aeruginosin and prenylagaramide for example, we found remarkable strain-specific chemo-diversity. Only few of the chemical features were common to the four studied strains. Additionally, the MS/MS data were analyzed using Global Natural Products Social Molecular Networking (GNPS) to identify molecular families of the same biosynthetic origin. In conclusion, we present an efficient integrative strategy for elucidating the chemical diversity of a given genus and link the data obtained from analytical chemistry to biosynthetic genes of cyanobacteria.


2021 ◽  
Vol 75 (6) ◽  
pp. 543-547
Author(s):  
Florian Hubrich ◽  
Alessandro Lotti ◽  
Thomas A. Scott ◽  
Jörn Piel

Nature has evolved a remarkable array of biosynthetic enzymes that install diverse chemistries into natural products (NPs), bestowing them with a range of important biological properties that are of considerable therapeutic value. This is epitomized by the ribosomally synthesized and post-translationally modified peptides (RiPPs), a class of peptide natural products that undergo extensive post-translational modifications to produce structurally diverse bioactive peptides. In this review, we provide an overview of our research into the proteusin RiPP family, describing characterized members and the maturation enzymes responsible for their unique chemical structures and biological activities. The diverse enzymology identified in the first two proteusin pathways highlights the enormous potential of the RiPP class for new lead structures and novel pharmacophore-installing maturases as biocatalytic tools for drug discovery efforts.


Antibiotics ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 928
Author(s):  
Melissa M. Cadelis ◽  
Brent R. Copp ◽  
Siouxsie Wiles

Natural products have been a great source for drug leads, due to a vast majority possessing unique chemical structures. Such an example is the protoilludane class of natural products which contain an annulated 5/6/4-ring system and are almost exclusively produced by fungi. They have been reported to possess a diverse range of bioactivities, including antimicrobial, antifungal and cytotoxic properties. In this review, we discuss the isolation, structure elucidation and any reported bioactivities of this compound class, including establishment of stereochemistry and any total syntheses of these natural products. A total of 180 protoilludane natural products, isolated in the last 70 years, from fungi, plant and marine sources are covered, highlighting their structural diversity and potential in drug discovery.


Marine Drugs ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 115 ◽  
Author(s):  
Amr El-Demerdash ◽  
Atanas G. Atanasov ◽  
Olaf K. Horbanczuk ◽  
Mohamed A. Tammam ◽  
Mamdouh Abdel-Mogib ◽  
...  

Marine natural products (MNPs) continue to be in the spotlight in the global drug discovery endeavor. Currently, more than 30,000 structurally diverse secondary metabolites from marine sources have been isolated, making MNPs a profound, renewable source to investigate novel drug compounds. Marine sponges of the genus Suberea (family: Aplysinellidae) are recognized as producers of bromotyrosine derivatives, which are considered distinct chemotaxonomic markers for the marine sponges belonging to the order Verongida. This class of compounds exhibits structural diversity, ranging from simple monomeric molecules to more complex molecular scaffolds, displaying a myriad of biological and pharmacological potentialities. In this review, a comprehensive literature survey covering the period of 1998–2018, focusing on the chemistry and biological/pharmacological activities of marine natural products from marine sponges of the genus Suberea, with special attention to the biogenesis of the different skeletons of halogenated compounds, is presented.


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