scholarly journals Baikalomycins A-C, New Aquayamycin-Type Angucyclines Isolated from Lake Baikal Derived Streptomyces sp. IB201691-2A

2020 ◽  
Vol 8 (5) ◽  
pp. 680
Author(s):  
Irina Voitsekhovskaia ◽  
Constanze Paulus ◽  
Charlotte Dahlem ◽  
Yuriy Rebets ◽  
Suvd Nadmid ◽  
...  
Keyword(s):  
Natural Products ◽  
Lake Baikal ◽  
Structure Elucidation ◽  
Genome Mining ◽  
Ecological Niches ◽  
Hydroxyl Groups ◽  
Streptomyces Sp ◽  
Drug Leads ◽  
Promising Source ◽  
Antiproliferative Activities

Natural products produced by bacteria found in unusual and poorly studied ecosystems, such as Lake Baikal, represent a promising source of new valuable drug leads. Here we report the isolation of a new Streptomyces sp. strain IB201691-2A from the Lake Baikal endemic mollusk Benedictia baicalensis. In the course of an activity guided screening three new angucyclines, named baikalomycins A–C, were isolated and characterized, highlighting the potential of poorly investigated ecological niches. Besides that, the strain was found to accumulate large quantities of rabelomycin and 5-hydroxy-rabelomycin, known shunt products in angucyclines biosynthesis. Baikalomycins A–C demonstrated varying degrees of anticancer activity. Rabelomycin and 5-hydroxy-rabelomycin further demonstrated antiproliferative activities. The structure elucidation showed that baikalomycin A is a modified aquayamycin with β-d-amicetose and two additional hydroxyl groups at unusual positions (6a and 12a) of aglycone. Baikalomycins B and C have alternating second sugars attached, α-l-amicetose and α-l-aculose, respectively. The gene cluster for baikalomycins biosynthesis was identified by genome mining, cloned using a transformation-associated recombination technique and successfully expressed in S. albus J1074. It contains a typical set of genes responsible for an angucycline core assembly, all necessary genes for the deoxy sugars biosynthesis, and three genes coding for the glycosyltransferase enzymes. Heterologous expression and deletion experiments allowed to assign the function of glycosyltransferases involved in the decoration of baikalomycins aglycone.

scholarly journals Recent Advances in Discovery of Lead Structures from Microbial Natural Products: Genomics- and Metabolomics-Guided Acceleration

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2542
Author(s):  
Linda Sukmarini
Keyword(s):  
Natural Products ◽  
Genome Mining ◽  
Screening Methods ◽  
Technological Advancement ◽  
Natural Origin ◽  
Drug Discovery And Development ◽  
New Methodologies ◽  
Analytical Instrumentation ◽  
Microbial Natural Products ◽  
Drug Leads

Natural products (NPs) are evolutionarily optimized as drug-like molecules and remain the most consistently successful source of drugs and drug leads. They offer major opportunities for finding novel lead structures that are active against a broad spectrum of assay targets, particularly those from secondary metabolites of microbial origin. Due to traditional discovery approaches’ limitations relying on untargeted screening methods, there is a growing trend to employ unconventional secondary metabolomics techniques. Aided by the more in-depth understanding of different biosynthetic pathways and the technological advancement in analytical instrumentation, the development of new methodologies provides an alternative that can accelerate discoveries of new lead-structures of natural origin. This present mini-review briefly discusses selected examples regarding advancements in bioinformatics and genomics (focusing on genome mining and metagenomics approaches), as well as bioanalytics (mass-spectrometry) towards the microbial NPs-based drug discovery and development. The selected recent discoveries from 2015 to 2020 are featured herein.

scholarly journals Draft Genome Sequence of Streptomyces sp. Strain IB2014011-1, Isolated from Trichoptera sp. Larvae of Lake Baikal

2017 ◽  
Vol 5 (17) ◽  
Author(s):  
Denis V. Axenov-Gribanov ◽  
Bogdan T. Tokovenko ◽  
Yuriy V. Rebets ◽  
Irina V. Voytsekhovskaya ◽  
Zhanna M. Shatilina ◽  
...  
Keyword(s):  
Lake Baikal ◽  
Genome Sequence ◽  
Environmental Conditions ◽  
Draft Genome ◽  
Draft Genome Sequence ◽  
Ancient Lake ◽  
Streptomyces Sp ◽  
Promising Source ◽  
Species Biodiversity

ABSTRACT Unique ecosystems with specific environmental conditions have been proven to be a promising source for isolation of new Actinobacteria strains. Ancient Lake Baikal is one of the greatest examples of an ecosystem with high species biodiversity and endemicity caused by long-lasting isolated evolution and stable environmental conditions. Herein we report the draft genome sequence of Streptomyces sp. strain IB2014011-1, which was isolated from insect Trichoptera sp. larvae collected at the bottom of Lake Baikal.

scholarly journals The myxocoumarins A and B fromStigmatella aurantiacastrain MYX-030

2013 ◽  
Vol 9 ◽  
pp. 2579-2585 ◽  
Author(s):  
Tobias A M Gulder ◽  
Snežana Neff ◽  
Traugott Schüz ◽  
Tammo Winkler ◽  
René Gees ◽  
...  
Keyword(s):  
Natural Products ◽  
Structure Elucidation ◽  
Biological Evaluation ◽  
Biologically Active ◽  
Antifungal Properties ◽  
Structural Framework ◽  
Stigmatella Aurantiaca ◽  
Promising Source ◽  
Active Natural

The myxobacterial strainStigmatella aurantiacaMYX-030 was selected as promising source for the discovery of new biologically active natural products by our screening methodology. The isolation, structure elucidation and initial biological evaluation of the myxocoumarins derived from this strain are described in this work. These compounds comprise an unusual structural framework and exhibit remarkable antifungal properties.

scholarly journals A Review of Fungal Protoilludane Sesquiterpenoid Natural Products

Antibiotics ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 928
Author(s):  
Melissa M. Cadelis ◽  
Brent R. Copp ◽  
Siouxsie Wiles
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Structure Elucidation ◽  
Structural Diversity ◽  
Ring System ◽  
Diverse Range ◽  
Total Syntheses ◽  
Chemical Structures ◽  
Drug Leads ◽  
Unique Chemical

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.

scholarly journals In silico study of natural compounds from sesame against COVID-19 by targeting Mpro, PLpro and RdRp

RSC Advances ◽  
2021 ◽  
Vol 11 (36) ◽  
pp. 22398-22408
Author(s):  
Ahmed E. Allam ◽  
Yhiya Amen ◽  
Ahmed Ashour ◽  
Hamdy K. Assaf ◽  
Heba Ali Hassan ◽  
...  
Keyword(s):  
Natural Products ◽  
Traditional Medicine ◽  
In Silico ◽  
Natural Compounds ◽  
New Drug ◽  
In Silico Study ◽  
Drug Leads ◽  
Promising Source

Natural products and traditional medicine products with known safety profiles are a promising source for the discovery of new drug leads.

scholarly journals Iron-meditated fungal starvation by lupine rhizosphere-associated and extremotolerant Streptomyces sp. S29 desferrioxamine production

2020 ◽  
Author(s):  
Scott A. Jarmusch ◽  
Diego Lagos-Susaeta ◽  
Emtinan Diab ◽  
Oriana Salazar ◽  
Juan A. Asenjo ◽  
...  
Keyword(s):  
Iron Uptake ◽  
Structure Elucidation ◽  
Chemical Potential ◽  
Wine Industry ◽  
Ecological Niches ◽  
Molecular Networking ◽  
Streptomyces Sp ◽  
Hydroxamate Siderophores ◽  
Fungal Phytopathogens ◽  
Chelating Compounds

ABSTRACTSiderophores are iron-chelating compounds that aid iron uptake, one of the key strategies for microorganisms to carve out ecological niches in microbially diverse environments. Desferrioxamines are the principal siderophores produced by Streptomyces spp. Their biosynthesis has been well studied and as a consequence, the chemical potential of the pathway continues to expand. With all of this in mind, our study aimed to explore extremotolerant and Lupine rhizosphere-derived Streptomyces sp. S29 for its potential antifungal capabilities. Cocultivation of isolate S29 was carried out with Aspergillus niger and Botrytis cinerea, both costly fungal phytopathogens in the wine industry, to simulate their interaction within the rhizosphere. The results indicate that not only is Streptomyces sp. S29 extraordinary at producing hydroxamate siderophores but uses siderophore production as a means to ‘starve’ the fungi of iron. High resolution LC-MS/MS followed by GNPS molecular networking was used to observe the datasets for desferrioxamines and guided structure elucidation of new desferrioxamine analogues. Comparing the new chemistry, using tools like molecular networking and MS2LDA, with the known biosynthesis, we show that the chemical potential of the desferrioxamine pathway has further room for exploration.

scholarly journals A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus Pseudosporangium

2020 ◽  
Vol 16 ◽  
pp. 1100-1110 ◽  
Author(s):  
Shun Saito ◽  
Kota Atsumi ◽  
Tao Zhou ◽  
Keisuke Fukaya ◽  
Daisuke Urabe ◽  
...  
Keyword(s):  
Natural Products ◽  
Pathogenic Fungus ◽  
Genome Mining ◽  
Culture Collection ◽  
Side Chain ◽  
Chemical Derivatization ◽  
Unusual Structure ◽  
Promising Source ◽  
Biosynthetic Machinery ◽  
Shift Calculation

Aside from the well-studied conventional actinomycetes such as Streptomyces, the less investigated genera of actinomycetes also represent a promising source of natural products. Genome mining indicated that members of the underexplored genus Pseudosporangium, from which no secondary metabolites have been reported to date, may harbor the biosynthetic machinery for the formation of novel natural products. The strain RD062863, that is available at a public culture collection, was obtained and subjected to metabolite analysis, which resulted in the discovery of a novel cyclopeptide, pseudosporamide (1), along with three new oligomycin-class polyketides, pseudosporamicins A–C (2–4). The unusual structure of compound 1, featured by a biaryl-bond bridging across a tripeptide scaffold, N-acetyl-ʟ-Tyr-ʟ-Pro-ʟ-Trp, was determined by a combination of spectroscopic analyses, chemical derivatization, ECD calculation, and DFT-based theoretical chemical shift calculation, revealing the presence of an (S a)-axial chirality around the biaryl bond. Compounds 2–4 lacked hydroxylation on the side chain of the spiroacetal rings, which showed clear contrast to other oligomycin congeners and related polyketides with ring-truncation or expansion. The new macrolides 2–4 displayed potent antimicrobial activity against the Gram-positive bacterium Kocuria rhizohpila and the plant pathogenic fungus Glomerella cingulata. All compounds showed moderate cytotoxicity against P388 murine leukemia cells with IC50 values in the micromolar to submicromolar ranges. These results exemplified the validity of phylogeny-focused strain selection combined with biosynthetic gene-directed genome mining for the efficient discovery of new natural products.

scholarly journals Mechanisms of Action of Ribosomally Synthesized and Posttranslationally Modified Peptides (RiPPs)

2021 ◽  
Author(s):  
Li Cao ◽  
Truc Do ◽  
A James Link
Keyword(s):  
Natural Products ◽  
Mechanism Of Action ◽  
Molecular Mechanisms ◽  
Structural Information ◽  
Genome Mining ◽  
Mechanisms Of Action ◽  
Detailed Mechanism ◽  
Modified Peptides ◽  
Drug Leads

Abstract Natural products remain a critical source of medicines and drug leads. One of the most rapidly growing superclasses of natural products is RiPPs: ribosomally synthesized and posttranslationally modified peptides. RiPPs have rich and diverse bioactivities. This review highlights examples of the molecular mechanisms of action that underly those bioactivities. Particular emphasis is placed on RiPP/target interactions for which there is structural information. This detailed mechanism of action work is critical toward the development of RiPPs as therapeutics and can also be used to prioritize hits in RiPP genome mining studies.

Expanding the Natural Products Heterologous Expression Repertoire in the Model Cyanobacterium Anabaena sp. Strain PCC 7120: Production of Pendolmycin and Teleocidin B-4

2019 ◽  
Author(s):  
Patrick Videau ◽  
Kaitlyn Wells ◽  
Arun Singh ◽  
Jessie Eiting ◽  
Philip Proteau ◽  
...  
Keyword(s):  
Natural Products ◽  
Genome Mining ◽  
Gene Clusters ◽  
Combinatorial Biosynthesis ◽  
Test Case ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Cyanobacterium Anabaena ◽  
Anabaena Sp ◽  
Pcc 7120

Cyanobacteria are prolific producers of natural products and genome mining has shown that many orphan biosynthetic gene clusters can be found in sequenced cyanobacterial genomes. New tools and methodologies are required to investigate these biosynthetic gene clusters and here we present the use of <i>Anabaena </i>sp. strain PCC 7120 as a host for combinatorial biosynthesis of natural products using the indolactam natural products (lyngbyatoxin A, pendolmycin, and teleocidin B-4) as a test case. We were able to successfully produce all three compounds using codon optimized genes from Actinobacteria. We also introduce a new plasmid backbone based on the native <i>Anabaena</i>7120 plasmid pCC7120ζ and show that production of teleocidin B-4 can be accomplished using a two-plasmid system, which can be introduced by co-conjugation.

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