Progress in Research on Bioactive Secondary Metabolites from Deep-Sea Derived Microorganisms

Deep sea has an extreme environment which leads to biodiversity of microorganisms and their unique physical and biochemical mechanisms. Deep-sea derived microorganisms are more likely to produce novel bioactive substances with special mechanism of action for drug discovery. This article reviews secondary metabolites with biological activities such as anti-tumor, anti-bacterial, anti-viral, and anti-inflammatory isolated from deep-sea fungi and bacteria during 2018–2020. Effective methods for screening and obtaining natural active compounds from deep-sea microorganisms are also summarized, including optimizing the culture conditions, using genome mining technology, biosynthesis and so on. The comprehensive application of these methods makes broader prospects for the development and application of deep sea microbial bioactive substances.

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Bioactive secondary metabolites produced by microorganisms associated with plants

Biologia ◽

10.2478/s11756-007-0044-1 ◽

2007 ◽

Vol 62 (3) ◽

Cited By ~ 105

Author(s):

Silvia Firáková ◽

Mária Šturdíková ◽

Marta Múčková

Keyword(s):

Secondary Metabolites ◽

Host Plants ◽

Biological Activities ◽

Bioactive Metabolites ◽

Intercellular Spaces ◽

Biotechnological Production ◽

Bioactive Substances ◽

The Past ◽

Endophytic Microorganisms ◽

Bioactive Secondary Metabolites

AbstractIn the past few decades groups of scientists have focused their study on relatively new microorganisms called endophytes. By definition these microorganisms, mostly fungi and bacteria, colonise the intercellular spaces of the plant tissues. The mutual relationship between endophytic microorganisms and their host plants, taxanomy and ecology of endophytes are being studied. Some of these microorganisms produce bioactive secondary metabolites that may be involved in a host-endophyte relationship. Recently, many endophytic bioactive metabolites, known as well as new substances, possesing a wide variety of biological activities as antibiotic, antitumor, antiinflammatory, antioxidant, etc. have been identified. The microorganisms such as endophytes may be very interesting for biotechnological production of bioactive substances as medicinally important agents. Therefore the aim of this review is to briefly characterize endophytes and summarize the structuraly different bioactive secondary metabolites produced by endophytic microorganisms as well as microbial sources of these metabolites and their host plants.

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Marine Actinomycetes-derived Natural Products

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666191114102359 ◽

2020 ◽

Vol 19 (31) ◽

pp. 2868-2918 ◽

Cited By ~ 3

Author(s):

Chengfang Yang ◽

Rui Qian ◽

Yao Xu ◽

Junxi Yi ◽

Yiwen Gu ◽

...

Keyword(s):

Natural Products ◽

Drug Discovery ◽

Secondary Metabolites ◽

Metabolic Pathways ◽

Biological Activities ◽

Living Environment ◽

Marine Actinomycetes ◽

Bioactive Substances ◽

Lead Compounds

: Actinomycetes is an abundant resource for discovering a large number of lead compounds, which play an important role in microbial drug discovery. Compared to terrestrial microorganisms, marine actinomycetes have unique metabolic pathways because of their special living environment, which has the potential to produce a variety of bioactive substances. In this paper, secondary metabolites isolated from marine actinomycetes are reviewed (2013-2018), most of which exhibited cytotoxic, antibacterial, and antiviral biological activities.

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Discovery of a polybrominated aromatic secondary metabolite from a planctomycete points at an ambivalent interaction with its macroalgae host

10.1101/723874 ◽

2019 ◽

Author(s):

Fabian Panter ◽

Ronald Garcia ◽

Angela Thewes ◽

Nestor Zaburannyi ◽

Boyke Bunk ◽

...

Keyword(s):

Secondary Metabolites ◽

Secondary Metabolite ◽

Biological Activities ◽

Genome Mining ◽

Gene Clusters ◽

Laboratory Culture ◽

Culture Conditions ◽

Herbicidal Activity ◽

Spectrometric Analysis ◽

Plant Toxin

AbstractThe roles of the majority of bacterial secondary metabolites, especially those from uncommon sources are yet elusive even though many of these compounds show striking biological activities. To further investigate the secondary metabolite repertoire of underexploited bacterial families, we chose to analyze a novel representative of the yet untapped bacterial phylum Planctomycetes for the production of secondary metabolites under laboratory culture conditions. Development of a planctomycetal high density cultivation technique in combination with high resolution mass spectrometric analysis revealed Planctomycetales strain 10988 to produce the plant toxin 3,5 dibromo p-anisic acid. This molecule represents the first secondary metabolite reported from any planctomycete. Genome mining revealed the biosynthetic origin of this doubly brominated secondary metabolite and a biosynthesis model for the com-pound was devised. Comparison of the biosynthetic route to biosynthetic gene clusters responsible for formation of polybrominated small aromatic compounds reveals evidence for an evolutionary link, while the compound’s herbicidal activity points towards an ambivalent role of the metabolite in the planctomycetal ecosystem.

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Bioactive Secondary Metabolites from Endophytic Fungi

Current Medicinal Chemistry ◽

10.2174/0929867326666190916144709 ◽

2020 ◽

Vol 27 (11) ◽

pp. 1836-1854 ◽

Cited By ~ 5

Author(s):

Elena Ancheeva ◽

Georgios Daletos ◽

Peter Proksch

Keyword(s):

Secondary Metabolites ◽

Endophytic Fungi ◽

Host Plants ◽

Biological Activities ◽

Cytotoxic Agents ◽

Special Focus ◽

Plant Metabolites ◽

Direct Production ◽

Bioactive Secondary Metabolites ◽

Fungal Genes

Background: Endophytes represent a complex community of microorganisms colonizing asymptomatically internal tissues of higher plants. Several reports have shown that endophytes enhance the fitness of their host plants by direct production of bioactive secondary metabolites, which are involved in protecting the host against herbivores and pathogenic microbes. In addition, it is increasingly apparent that endophytes are able to biosynthesize medicinally important “phytochemicals”, originally believed to be produced only by their host plants. Objective: The present review provides an overview of secondary metabolites from endophytic fungi with pronounced biological activities covering the literature between 2010 and 2017. Special focus is given on studies aiming at exploration of the mode of action of these metabolites towards the discovery of leads from endophytic fungi. Moreover, this review critically evaluates the potential of endophytic fungi as alternative sources of bioactive “plant metabolites”. Results: Over the past few years, several promising lead structures from endophytic fungi have been described in the literature. In this review, 65 metabolites are outlined with pronounced biological activities, primarily as antimicrobial and cytotoxic agents. Some of these metabolites have shown to be highly selective or to possess novel mechanisms of action, which hold great promises as potential drug candidates. Conclusion: Endophytes represent an inexhaustible reservoir of pharmacologically important compounds. Moreover, endophytic fungi could be exploited for the sustainable production of bioactive “plant metabolites” in the future. Towards this aim, further insights into the dynamic endophyte - host plant interactions and origin of endophytic fungal genes would be of utmost importance.

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Bioactive secondary metabolites from the deep-sea derived fungus Aspergillus sp. SCSIO 41029

The Journal of Antibiotics ◽

10.1038/s41429-020-00378-y ◽

2020 ◽

Vol 74 (2) ◽

pp. 156-159

Author(s):

Weihao Chen ◽

Chunmei Chen ◽

Jieyi Long ◽

Sujuan Lan ◽

Xiuping Lin ◽

...

Keyword(s):

Secondary Metabolites ◽

Deep Sea ◽

Bioactive Secondary Metabolites ◽

Aspergillus Sp

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Genomic and Metabolomic Analysis of Antarctic Bacteria Revealed Culture and Elicitation Conditions for the Production of Antimicrobial Compounds

Biomolecules ◽

10.3390/biom10050673 ◽

2020 ◽

Vol 10 (5) ◽

pp. 673

Author(s):

Kattia Núñez-Montero ◽

Damián Quezada-Solís ◽

Zeinab G. Khalil ◽

Robert J. Capon ◽

Fernando D. Andreote ◽

...

Keyword(s):

Antibacterial Activity ◽

Secondary Metabolites ◽

Culture Media ◽

Genome Mining ◽

Gene Clusters ◽

Culture Conditions ◽

Bioactive Metabolites ◽

Bacterial Strains ◽

Antarctic Bacteria ◽

New Antibiotics

Concern about finding new antibiotics against drug-resistant pathogens is increasing every year. Antarctic bacteria have been proposed as an unexplored source of bioactive metabolites; however, most biosynthetic gene clusters (BGCs) producing secondary metabolites remain silent under common culture conditions. Our work aimed to characterize elicitation conditions for the production of antibacterial secondary metabolites from 34 Antarctic bacterial strains based on MS/MS metabolomics and genome mining approaches. Bacterial strains were cultivated under different nutrient and elicitation conditions, including the addition of lipopolysaccharide (LPS), sodium nitroprusside (SNP), and coculture. Metabolomes were obtained by HPLC-QTOF-MS/MS and analyzed through molecular networking. Antibacterial activity was determined, and seven strains were selected for genome sequencing and analysis. Biosynthesis pathways were activated by all the elicitation treatments, which varies among strains and dependents of culture media. Increased antibacterial activity was observed for a few strains and addition of LPS was related with inhibition of Gram-negative pathogens. Antibiotic BGCs were found for all selected strains and the expressions of putative actinomycin, carotenoids, and bacillibactin were characterized by comparison of genomic and metabolomic data. This work established the use of promising new elicitors for bioprospection of Antarctic bacteria and highlights the importance of new “-omics” comparative approaches for drug discovery.

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Genome mining of a marine-derived Streptomyces sp. PDH23 isolated from sponge in Da Nang sea for secondary metabolite gene clusters

Vietnam Journal of Biotechnology ◽

10.15625/1811-4989/18/4/14970 ◽

2021 ◽

Vol 18 (4) ◽

pp. 709-721

Author(s):

Le Ngoc Giang ◽

Le Thi Hong Minh ◽

Vu Thi Quyen ◽

Nguyen Mai Anh ◽

Nguyen Thi Kim Cuc ◽

...

Keyword(s):

Secondary Metabolites ◽

Antimicrobial Agents ◽

Biological Activities ◽

Wide Spectrum ◽

Genome Mining ◽

Gc Content ◽

Gene Clusters ◽

Gram Positive ◽

16S Rrna Analysis ◽

Streptomyces Sp

The streptomyces is one of the best characterized ubiquitous filamentous bacteria from the actinobacteriaclass. They are known to produce thousands of specialized metabolite biosynthesis gene clusters (SMBG). Their SMBG clusters have multiple activities ranging from antimicrobial, antitumor, antiviral and probiotic. Streptomyces strain and their isolates with interesting biological activities against gram-positive and gram-negative indicator strains was recently characterised. Currently, they are employed in more than half of all antibiotics used in human and veterinary medicine. With the increase in drug resistance bacteria, it is important to mine for new natural chemicals.In this study, screening via disk-diffusion agar method revealed that Streptomyces sp. PDH23 isolated from the Rhabdastrellaglobostellata marine sponge sample from Da Nang, Vietnam produce antimicrobial agents with a wide spectrum of activities. This species can produce highly active enzymes, which breakdown celluloses, amyloses and proteins. On top of that they are shown to restrict the grow of the gram positive Bacillus cereus ATCC14579 (BC), Staphylococcus aureus ATCC25923 (SA), the gram-negativeVibrio parahaemolyticus ATCC17802 (VP) and the Candida albicans ATCC10231 fungus (CA). They are antimethicillin-resistant S. aureus(MRSA) ATCC33591 andmethicillin-resistantS. epidermidis (MRSE) ATCC35984. The taxonomy of PDH23 was characterized using 16S rRNA analysis. Whole genome sequencing of PDH23 showed 8594820 base pairs with GC content of 72.03%. Mining of secondary metabolites reveals gene clusters responsible for the biosynthesis of known and/or novel secondary metabolites, including different types of terpene, NRPS-like , PKS, PKS-like, hglE-KS, betalactone, melanin, t1pks, t2pks, t3pks, nrps, indole, siderophore, bacteriocin, ectoine, butyrolactone, phenazine.

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Genome mining and UHPLC-MS/MS illuminate the specificity of secondary metabolite synthetic gene clusters in Bacillus subtilis NCD-2

10.21203/rs.3.rs-33091/v1 ◽

2020 ◽

Author(s):

Zhenhe Su ◽

Xiuye Chen ◽

Xiaomeng Liu ◽

Qinggang Guo ◽

Shezeng Li ◽

...

Keyword(s):

Bacillus Subtilis ◽

Secondary Metabolites ◽

Secondary Metabolite ◽

Biological Activities ◽

Genome Mining ◽

Gene Clusters ◽

Synthetic Gene ◽

Integrative Approach ◽

Amino Acid Sequence Similarity ◽

Genetic Characteristics

Abstract Background Bacillus subtilisstrain NCD-2 is anexcellent biocontrol agent against plant soil-borne diseases and shows broad-spectrum antifungal activities. This study aimed to explore all the secondary metabolite synthetic gene clusters and related bioactive compounds in NCD-2. An integrative approach, which coupled genome mining with structural identification technologies using ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry (UHPLC-MS/MS), was conducted to interpret the chemical origins of the significant biological activities in NCD-2. Results Genome mining revealed that NCD-2 contained nine gene clustershaving predicted functionsinvolving secondary metabolites with bioactive abilities. They encoded six known products-fengycin, surfactin, bacillaene, subtilosin, bacillibactin, and bacilysin-as well as three unknown products.Interestingly, the synthetic gene clusters for surfactin and fengycin showed 83% and 92% amino acid sequence similarity levels with the corresponding productsin Bacillus velezensisstrain FZB42. A further comparison of gene clusters encoding fengycin and surfactinrevealed that strain NCD-2 had lost thefenC and fenDgenes in the fengycinbiosynthetic operon, and that the surfactin synthetic enzyme-related gene srfAB was divided into two parts.Abioinformatics analysis showed that fenEAmay function as fenCD in synthesizing fengycinand that the structure of thisfengycin synthetic gene clusteris likely unique to NCD-2.Five kinds of fengycin,with 26 homologs, and surfactin,with 4 homologs,were detectedfrom strain NCD-2, which indicated the non-typical and unique nature of this fengycin biosynthetic gene cluster.To the best of our knowledge, this is the first report of a non-typical gene cluster related to fengycin synthesis. Conclusions The data provide the genetic characteristics of secondary metabolite synthetic gene clusters for fengycinand surfactin in B. subtilis NCD-2, including the unique synthetic mechanism for fengycin, and suggest that bioactive secondary metabolites explain the biological activities of NCD-2.

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The Chemistry, Biochemistry and Pharmacology of Marine Natural Products from Leptolyngbya, a Chemically Endowed Genus of Cyanobacteria

Marine Drugs ◽

10.3390/md18100508 ◽

2020 ◽

Vol 18 (10) ◽

pp. 508

Author(s):

Yueying Li ◽

C. Benjamin Naman ◽

Kelsey L. Alexander ◽

Huashi Guan ◽

William H. Gerwick

Keyword(s):

Nitrogen Fixation ◽

Drug Discovery ◽

Secondary Metabolites ◽

Primary Productivity ◽

Algal Blooms ◽

Biological Activities ◽

Biosynthetic Pathways ◽

Drug Discovery And Development ◽

Ecological Habitats ◽

Product Chemistry

Leptolyngbya, a well-known genus of cyanobacteria, is found in various ecological habitats including marine, fresh water, swamps, and rice fields. Species of this genus are associated with many ecological phenomena such as nitrogen fixation, primary productivity through photosynthesis and algal blooms. As a result, there have been a number of investigations of the ecology, natural product chemistry, and biological characteristics of members of this genus. In general, the secondary metabolites of cyanobacteria are considered to be rich sources for drug discovery and development. In this review, the secondary metabolites reported in marine Leptolyngbya with their associated biological activities or interesting biosynthetic pathways are reviewed, and new insights and perspectives on their metabolic capacities are gained.

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Natural Products from Deep-Sea-Derived Fungi ̶ A New Source of Novel Bioactive Compounds?

Current Medicinal Chemistry ◽

10.2174/0929867324666170314150121 ◽

2018 ◽

Vol 25 (2) ◽

pp. 186-207 ◽

Cited By ~ 22

Author(s):

Georgios Daletos ◽

Weaam Ebrahim ◽

Elena Ancheeva ◽

Mona El-Neketi ◽

Weiguo Song ◽

...

Keyword(s):

Natural Products ◽

Drug Discovery ◽

Secondary Metabolites ◽

Bioactive Compounds ◽

Deep Sea ◽

Underlying Assumption ◽

Pharmacologically Active ◽

Promising Source ◽

New Metabolites

Background: Over the last two decades, deep-sea-derived fungi are considered to be a new source of pharmacologically active secondary metabolites for drug discovery mainly based on the underlying assumption that the uniqueness of the deep sea will give rise to equally unprecedented natural products. Indeed, up to now over 200 new metabolites have been identified from deep-sea fungi, which is in support of the statement made above. Results: This review summarizes the new and/or bioactive compounds reported from deepsea- derived fungi in the last six years (2010 – October 2016) and critically evaluates whether the data published so far really support the notion that these fungi are a promising source of new bioactive chemical entities.

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