Isolation and optimized production of putative antimicrobial compounds from Egyptian soil isolate Streptomyces sp. MS. 10

Abstract Background The rapid spread of antibiotic resistance has increased research interest in the discovery of natural products, mainly from actinomycetes, which have been the primary source of antimicrobial compounds. This study aimed to isolate, characterize, and optimize the production of some of the bioactive compounds from bioactive soil actinomycetes. Results One promising soil actinomycete, which was molecularly identified as Streptomyces sp. and designated as Streptomyces sp. MS. 10, showed broad-spectrum antimicrobial activity, including activity against methicillin-resistant Staphylococcus aureus. Thus, it was selected for isolation of its major bioactive compounds. Polymerase chain reaction amplification of the genes responsible for antibiotic biosynthesis showed the presence of genes encoding type I and type II polyketide synthase. Liquid chromatography-mass spectrometry analysis found that the major antimicrobial compounds produced by Streptomyces sp. MS. 10 were weakly ionized bioactive secondary metabolites. A large-scale fermentation experiment of Streptomyces sp. MS. 10 using pre-optimized culture conditions followed by bioassay-guided chromatographic separation of its secondary metabolites resulted in the isolation of putative bioactive compounds that were identified as fatty acids using proton nuclear magnetic resonance spectroscopy. Conclusions Egyptian soil is still a good source for exploring bioactive actinomycetes. Additionally, this study highlighted the importance of combining both physicochemical and genotypic characterization with spectroscopic analysis of the major natural products when isolating bioactive metabolites.

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Taxonomy, Diversity and Cultivation of the Oudemansielloid/Xeruloid Taxa Hymenopellis, Mucidula, Oudemansiella, and Xerula with Respect to Their Bioactivities: A Review

Journal of Fungi ◽

10.3390/jof7010051 ◽

2021 ◽

Vol 7 (1) ◽

pp. 51

Author(s):

Allen Grace Niego ◽

Olivier Raspé ◽

Naritsada Thongklang ◽

Rawiwan Charoensup ◽

Saisamorn Lumyong ◽

...

Keyword(s):

Secondary Metabolites ◽

Bioactive Compounds ◽

State Of The Art ◽

Bioactive Metabolites ◽

High Quality ◽

Important Resource ◽

Molecular Weights ◽

Anti Cancer ◽

Potential Applications ◽

Commercial Applications

The oudemansielloid/xeruloid taxa Hymenopellis, Mucidula, Oudemansiella, and Xerula are genera of Basidiomycota that constitute an important resource of bioactive compounds. Numerous studies have shown antimicrobial, anti-oxidative, anti-cancer, anti-inflammatory and other bioactivities of their extracts. The bioactive principles can be divided into two major groups: (a) hydrophilic polysaccharides with relatively high molecular weights and (b) low molecular medium polar secondary metabolites, such as the antifungal strobilurins. In this review, we summarize the state of the art on biodiversity, cultivation of the fungi and bioactivities of their secondary metabolites and discuss future applications. Although the strobilurins are well-documented, with commercial applications as agrochemical fungicides, there are also other known compounds from this group that have not yet been well-studied. Polysaccharides, dihydro-citrinone phenol A acid, scalusamides, and acetylenic lactones such as xerulin, also have potential applications in the nutraceutical, pharmaceutical and medicinal market and should be further explored. Further studies are recommended to isolate high quality bioactive compounds and fully understand their modes of action. Given that only few species of oudemansielloid/xeruloid mushrooms have been explored for their production of secondary metabolites, these taxa represent unexplored sources of potentially useful and novel bioactive metabolites.

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Origins and Bioactivities of Natural Compounds Derived from Marine Ascidians and Their Symbionts

Marine Drugs ◽

10.3390/md17120670 ◽

2019 ◽

Vol 17 (12) ◽

pp. 670 ◽

Cited By ~ 6

Author(s):

Xiaoju Dou ◽

Bo Dong

Keyword(s):

Natural Products ◽

Secondary Metabolites ◽

Bioactive Compounds ◽

Natural Compounds ◽

Marine Animals ◽

Lead Compounds ◽

Chemical Structures ◽

Complex Interactions ◽

Novel Structures ◽

Important Drug

Marine ascidians are becoming important drug sources that provide abundant secondary metabolites with novel structures and high bioactivities. As one of the most chemically prolific marine animals, more than 1200 inspirational natural products, such as alkaloids, peptides, and polyketides, with intricate and novel chemical structures have been identified from ascidians. Some of them have been successfully developed as lead compounds or highly efficient drugs. Although numerous compounds that exist in ascidians have been structurally and functionally identified, their origins are not clear. Interestingly, growing evidence has shown that these natural products not only come from ascidians, but they also originate from symbiotic microbes. This review classifies the identified natural products from ascidians and the associated symbionts. Then, we discuss the diversity of ascidian symbiotic microbe communities, which synthesize diverse natural products that are beneficial for the hosts. Identification of the complex interactions between the symbiont and the host is a useful approach to discovering ways that direct the biosynthesis of novel bioactive compounds with pharmaceutical potentials.

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Use of proton nuclear magnetic resonance spectroscopy in detection and study of organic acidurias.

Clinical Chemistry ◽

10.1093/clinchem/31.11.1795 ◽

1985 ◽

Vol 31 (11) ◽

pp. 1795-1801 ◽

Cited By ~ 81

Author(s):

R A Iles ◽

A J Hind ◽

R A Chalmers

Keyword(s):

Nuclear Magnetic Resonance ◽

Magnetic Resonance ◽

Magnetic Resonance Spectroscopy ◽

Nuclear Magnetic Resonance Spectroscopy ◽

Clinical Care ◽

Proton Nuclear Magnetic Resonance ◽

Resonance Spectroscopy ◽

Type I ◽

Organic Acidurias ◽

Nuclear Magnetic

Abstract We used high-resolution proton nuclear magnetic resonance spectroscopy to detect, identify, and study the major normal and abnormal organic acid metabolites in urine from patients with propionic acidemia, methylmalonic aciduria, branched-chain ketoaciduria, isovaleric acidemia, and glutaric aciduria type I. Characteristic and diagnostic spectra were obtained at 400 MHz for each disorder in all the patients studied and neutral and basic compounds, including amino acids and acylcarnitines, were also detected. The technique is rapid (10 min) and requires small samples (0.5 mL) and no preliminary extraction or derivative preparation. We believe that it is particularly suitable for the rapid and acute diagnosis of inborn errors of metabolism, especially the organic acidurias, and for acute pediatric clinical care, when rapid monitoring of major metabolic alterations is required in a time scale suitable to influence directly and immediately the therapy of the patients concerned.

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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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Marine Rare Actinomycetes: A Promising Source of Structurally Diverse and Unique Novel Natural Products

Marine Drugs ◽

10.3390/md17050249 ◽

2019 ◽

Vol 17 (5) ◽

pp. 249 ◽

Cited By ~ 29

Author(s):

Subramani ◽

Sipkema

Keyword(s):

Natural Products ◽

New Species ◽

Secondary Metabolites ◽

Natural Product ◽

Bioactive Compounds ◽

Marine Environment ◽

Present Knowledge ◽

Bioactive Natural Products ◽

Rare Actinomycetes ◽

Promising Source

Rare actinomycetes are prolific in the marine environment; however, knowledge about their diversity, distribution and biochemistry is limited. Marine rare actinomycetes represent a rather untapped source of chemically diverse secondary metabolites and novel bioactive compounds. In this review, we aim to summarize the present knowledge on the isolation, diversity, distribution and natural product discovery of marine rare actinomycetes reported from mid-2013 to 2017. A total of 97 new species, representing 9 novel genera and belonging to 27 families of marine rare actinomycetes have been reported, with the highest numbers of novel isolates from the families Pseudonocardiaceae, Demequinaceae, Micromonosporaceae and Nocardioidaceae. Additionally, this study reviewed 167 new bioactive compounds produced by 58 different rare actinomycete species representing 24 genera. Most of the compounds produced by the marine rare actinomycetes present antibacterial, antifungal, antiparasitic, anticancer or antimalarial activities. The highest numbers of natural products were derived from the genera Nocardiopsis, Micromonospora, Salinispora and Pseudonocardia. Members of the genus Micromonospora were revealed to be the richest source of chemically diverse and unique bioactive natural products.

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SeMPI 2.0—A Web Server for PKS and NRPS Predictions Combined with Metabolite Screening in Natural Product Databases

Metabolites ◽

10.3390/metabo11010013 ◽

2020 ◽

Vol 11 (1) ◽

pp. 13

Author(s):

Paul F. Zierep ◽

Adriana T. Ceci ◽

Ilia Dobrusin ◽

Sinclair C. Rockwell-Kollmann ◽

Stefan Günther

Keyword(s):

Natural Products ◽

Secondary Metabolites ◽

Building Block ◽

Web Server ◽

Gene Clusters ◽

Type I ◽

Biosynthetic Gene ◽

Biosynthetic Gene Clusters ◽

A Genome ◽

Wide Range

Microorganisms produce secondary metabolites with a remarkable range of bioactive properties. The constantly increasing amount of published genomic data provides the opportunity for efficient identification of biosynthetic gene clusters by genome mining. On the other hand, for many natural products with resolved structures, the encoding biosynthetic gene clusters have not been identified yet. Of those secondary metabolites, the scaffolds of nonribosomal peptides and polyketides (type I modular) can be predicted due to their building block-like assembly. SeMPI v2 provides a comprehensive prediction pipeline, which includes the screening of the scaffold in publicly available natural compound databases. The screening algorithm was designed to detect homologous structures even for partial, incomplete clusters. The pipeline allows linking of gene clusters to known natural products and therefore also provides a metric to estimate the novelty of the cluster if a matching scaffold cannot be found. Whereas currently available tools attempt to provide comprehensive information about a wide range of gene clusters, SeMPI v2 aims to focus on precise predictions. Therefore, the cluster detection algorithm, including building block generation and domain substrate prediction, was thoroughly refined and benchmarked, to provide high-quality scaffold predictions. In a benchmark based on 559 gene clusters, SeMPI v2 achieved comparable or better results than antiSMASH v5. Additionally, the SeMPI v2 web server provides features that can help to further investigate a submitted gene cluster, such as the incorporation of a genome browser, and the possibility to modify a predicted scaffold in a workbench before the database screening.

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Genome-wide analysis and prediction of genes involved in the biosynthesis of polysaccharides and bioactive secondary metabolites in high-temperature-tolerant of wild Flammulina filiformis

10.21203/rs.2.13424/v2 ◽

2019 ◽

Author(s):

Juan Chen ◽

Jia-Mei Li ◽

Yan-Jing Tang ◽

Ke Ma ◽

Bing Li ◽

...

Keyword(s):

Secondary Metabolites ◽

Bioactive Compounds ◽

Fruiting Body ◽

Polyketide Synthase ◽

Developmental Stages ◽

Glucose Dehydrogenase ◽

Wild Strain ◽

Gene Clusters ◽

Type I ◽

Terpenoid Biosynthesis

Abstract Background: Flammulina filiformis (=Asian “F.velutipes”) is a popular commercial edible mushroom. Many bioactive compounds with medicinal effects, such as polysaccharides and sesquiterpenoids, have been isolated and identified from F. filiformis, but their biosynthesis and regulation at the molecular level remains unclear. In this study, we sequenced the genome of the wild strain F. filiformis Liu355, predicated its the biosynthetic gene clusters (BGCs) and profiled the expression of these genes in wild and cultivar strains and in different developmental stages of the wild F. filiformis strain by a comparative transcriptomic analysis. Results: We found that the genome of the F. filiformis was 35.01 M bp in length and harbored 10396 gene models. Thirteen putative terpenoid gene clusters were predicted and 12 sesquiterpene synthase genes belonging to four different groups and two type I polyketide synthase gene clusters were identified in the F. filiformis genome. The number of genes related to terpenoid biosynthesis was higher in the wild strain (119 genes) than in the cultivar strain (81 genes). Most terpenoid biosynthesis genes were upregulated in the primordium and fruiting body of the wild strain, while the polyketide synthase genes were generally upregulated in the mycelium of the wild strain. Moreover, genes encoding UDP-glucose pyrophosphorylase and UDP-glucose dehydrogenase, which are involved in polysaccharide biosynthesis, had relatively high transcript levels both in the mycelium and fruiting body of the wild F. filiformis strain. Conclusions: F. filiformis is enriched in a number of gene clusters involved in the biosynthesis of polysaccharides and terpenoid bioactive compounds and these genes usually display differential expression between wild and cultivar strains, even in different developmental stages. This study expands our knowledge of the biology of F. filiformis and provides valuable data for elucidating the regulation of secondary metabolites in this unique F. filiformis strain.

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Expanding the Scope of Detectable Microbial Natural Products by Complementary Analytical Methods and Cultivation Systems

10.26434/chemrxiv.12497537.v1 ◽

2020 ◽

Author(s):

Chantal Bader ◽

Patrick Haack ◽

Fabian Panter ◽

Daniel Krug ◽

Rolf Müller

Keyword(s):

Natural Products ◽

Secondary Metabolites ◽

Genetic Manipulation ◽

Biosynthetic Gene Cluster ◽

Mass Spectrometry Analysis ◽

Ion Cyclotron Resonance ◽

Spectrometry Analysis ◽

Molecular Features ◽

Micro Organisms ◽

Microbial Natural Products

Recent advances in genome sequencing unveiled a large discrepancy between the genome-encoded capacity of micro-organisms to produce secondary metabolites and the number of natural products (NP) actually detected in their extracts. In order connect biosynthetic gene cluster diversity to NPs, common approaches include genetic manipulation of producers and diversifying the cultivation conditions. However, the range of detectable metabolites is fundamentally limited by the applied analytical method. In this work, we present a two-platform mass spectrometry analysis for the comprehensive secondary metabolomics characterization of nine myxobacterial strains. We evaluated direct infusion (DI) measurements of crude extracts on a Fourier Transform Ion Cyclotron Resonance (FTICR) mass spectrometer and compared them to measurements conducted on a Time-Of-Flight (TOF) device coupled to liquid chromatography (LC), a setup widely used in NP laboratories. We demonstrate that both methods are likewise successful to detect known metabolites, whereas statistical analysis of unknowns highlights their complementarity: strikingly, 82-99% molecular features were only found with one of the analytical setups. In addition, we evaluated NP profile differences seen from our set of strains grown in liquid culture versus their swarming colonies on agar plates. The detection of 21-96% more molecular features when both liquid and plate cultures were ana-lyzed (compared to only one of them) translates into increased chances to identify new NPs. Determination of strain-specific compounds in combination with GNPS molecular networking revealed strain Mx3 as particularly promising in terms of isolation and structure elucidation of novel secondary metabolites.

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Expanding the Scope of Detectable Microbial Natural Products by Complementary Analytical Methods and Cultivation Systems

10.26434/chemrxiv.12497537 ◽

2020 ◽

Author(s):

Chantal Bader ◽

Patrick Haack ◽

Fabian Panter ◽

Daniel Krug ◽

Rolf Müller

Keyword(s):

Natural Products ◽

Secondary Metabolites ◽

Genetic Manipulation ◽

Biosynthetic Gene Cluster ◽

Mass Spectrometry Analysis ◽

Ion Cyclotron Resonance ◽

Spectrometry Analysis ◽

Molecular Features ◽

Micro Organisms ◽

Microbial Natural Products

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Screening and Isolation of Associated Bioactive Microorganisms fromFasciospongia cavernosafrom of Visakhapatnam Coast, Bay of Bengal

E-Journal of Chemistry ◽

10.1155/2012/873203 ◽

2012 ◽

Vol 9 (4) ◽

pp. 2166-2176

Author(s):

P. Shamsher Kumar ◽

E. Radha Krishna ◽

P. Sujatha ◽

B. Veerendra Kumar

Keyword(s):

Secondary Metabolites ◽

Bay Of Bengal ◽

Antimicrobial Activities ◽

Middle Part ◽

Marine Sponges ◽

Bioactive Metabolites ◽

Antimicrobial Compounds ◽

Human Therapy ◽

Effective Drugs ◽

Visakhapatnam Coast

Nature, especially the marine environment, provides the most effective drugs used in human therapy. Among the metazoans, the marine sponges produce the most potent and highly selective bioactive secondary metabolites. These animals (or their associated symbiotic microorganisms) synthesize secondary metabolites whose activity and selectivity has developed during their long evolutionary history. During the course of exploitation of these resources two marine sponges,Fasciospongia cavernosa doc var.brown (dark brown) Fasciospongia cavernosa doc var.yellow (yellow)collected from the visakhapatnam coast of Bay of Bengal were investigated in order to assess the potential of these microorganisms for the production of antimicrobial compounds. The aqueous and organic extracts of both the sponges showed broad spectrum antibiotic activity. In this study a total of 178 microorganisms were isolated from different parts of two sponges and most of them from middle part of the sponge. The isolates were investigated in order to assess the potential of these microorganisms for the production of antimicrobial compounds. Testing for antimicrobial activities were performed against Gram-positive (Staphylococcus aureus, Bacillus subtilis, Bacillus cereus) Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli, Proteus vulgaris), fungi (Candida albicans, Aspergillus niger) and 10 pathogenic organisms. Resulting mean diameter of inhibition zones revealed isolates B4 & B6 were the most potent of all the isolates. The present study has revealed the presence of high numbers of diverse culturable microorganisms associated with the marine sponges from Visakhapatnam Coast of Bay of Bengal as well as their potential to produce bioactive metabolites.

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