Isolation and Identification of Pentalenolactone Analogs from Streptomyces sp. NRRL S-4

Terpene synthases are widely distributed in Actinobacteria. Genome sequencing of Streptomyces sp. NRRL S-4 uncovered a biosynthetic gene cluster (BGC) that putatively synthesizes pentalenolactone type terpenes. Guided by genomic information, the S-4 strain was chemically investigated, resulting in the isolation of two new sesquiterpenoids, 1-deoxy-8α-hydroxypentalenic acid (1) and 1-deoxy-9β-hydroxy-11-oxopentalenic acid (2), as shunt metabolites of the pentalenolactone (3) biosynthesis pathway. Their structures and absolute configurations were elucidated by analyses of HRESIMS and NMR spectroscopic data as well as time-dependent density functional theory/electronic circular dichroism (TDDFT/ECD) calculations. Compounds 1 and 2 exhibited moderate antimicrobial activities against Gram-positive and Gram-negative bacteria. These results confirmed that the pentalenolactone pathway was functional in this organism and will facilitate efforts for exploring Actinobacteria using further genome mining strategies.

Download Full-text

Genome Mining Coupled with OSMAC-Based Cultivation Reveal Differential Production of Surugamide A by the Marine Sponge Isolate Streptomyces sp. SM17 When Compared to Its Terrestrial Relative S. albidoflavus J1074

Microorganisms ◽

10.3390/microorganisms7100394 ◽

2019 ◽

Vol 7 (10) ◽

pp. 394 ◽

Cited By ~ 5

Author(s):

Eduardo Almeida ◽

Navdeep Kaur ◽

Laurence Jennings ◽

Andrés Felipe Carrillo Rincón ◽

Stephen Jackson ◽

...

Keyword(s):

Marine Sponge ◽

Carbon Catabolite Repression ◽

Marine Invertebrates ◽

Genome Mining ◽

Biosynthetic Gene Cluster ◽

Biosynthetic Gene ◽

Streptomyces Sp ◽

Streptomyces Albidoflavus ◽

Recent Interest ◽

New Compounds

Much recent interest has arisen in investigating Streptomyces isolates derived from the marine environment in the search for new bioactive compounds, particularly those found in association with marine invertebrates, such as sponges. Among these new compounds recently identified from marine Streptomyces isolates are the octapeptidic surugamides, which have been shown to possess anticancer and antifungal activities. By employing genome mining followed by an one strain many compounds (OSMAC)-based approach, we have identified the previously unreported capability of a marine sponge-derived isolate, namely Streptomyces sp. SM17, to produce surugamide A. Phylogenomics analyses provided novel insights on the distribution and conservation of the surugamides biosynthetic gene cluster (sur BGC) and suggested a closer relatedness between marine-derived sur BGCs than their terrestrially derived counterparts. Subsequent analysis showed differential production of surugamide A when comparing the closely related marine and terrestrial isolates, namely Streptomyces sp. SM17 and Streptomyces albidoflavus J1074. SM17 produced higher levels of surugamide A than S. albidoflavus J1074 under all conditions tested, and in particular producing >13-fold higher levels when grown in YD and 3-fold higher levels in SYP-NaCl medium. In addition, surugamide A production was repressed in TSB and YD medium, suggesting that carbon catabolite repression (CCR) may influence the production of surugamides in these strains.

Download Full-text

Complete Genome Sequence of Streptomyces sp. Strain BSE7F, a Bali Mangrove Sediment Actinobacterium with Antimicrobial Activities

Genome Announcements ◽

10.1128/genomea.00618-18 ◽

2018 ◽

Vol 6 (26) ◽

Cited By ~ 1

Author(s):

Ira Handayani ◽

Shanti Ratnakomala ◽

Puspita Lisdiyanti ◽

Fahrurrozi ◽

Mohammad Alanjary ◽

...

Keyword(s):

Genome Sequence ◽

Complete Genome Sequence ◽

Complete Genome ◽

Antimicrobial Activities ◽

Mangrove Sediment ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Content Type ◽

Streptomyces Sp ◽

Gram Positive Bacteria

The strain Streptomyces sp. BSE7F, a novel Streptomyces strain isolated from Indonesian mangrove sediment, displays antimicrobial activities against Gram-positive bacteria, Gram-negative bacteria, and yeast.

Download Full-text

Molecular Modeling, Density Functional Theory, ADME Prediction and Antimicrobial Activity Studies of 2-(substituted)oxazolo[4,5-b]pyridine Derivatives

New Journal of Chemistry ◽

10.1039/d1nj00701g ◽

2021 ◽

Author(s):

Ismail Celik ◽

Meryem Erol ◽

Gulcan Kuyucuklu

Keyword(s):

Density Functional Theory ◽

Antimicrobial Activity ◽

Molecular Modeling ◽

Density Functional ◽

Antimicrobial Activities ◽

Drug Resistant ◽

Pyridine Derivatives ◽

Functional Theory ◽

Adme Prediction ◽

Microdilution Method

In this study, the antimicrobial activities of previously synthesized 2-(substituted)oxazolo[4,5-b]pyridine derivatives on six bacteria, their twelve drug-resistant isolates, one fungus and two drug-resistant isolates were investigated by microdilution method. P6...

Download Full-text

New Sulfur-Containing Polyarsenicals from the New Caledonian Sponge Echinochalina bargibanti

Marine Drugs ◽

10.3390/md16100382 ◽

2018 ◽

Vol 16 (10) ◽

pp. 382 ◽

Cited By ~ 2

Author(s):

Petri Tähtinen ◽

Graziano Guella ◽

Giacomo Saielli ◽

Cécile Debitus ◽

Edouard Hnawia ◽

...

Keyword(s):

Mass Spectra ◽

Density Functional ◽

Antimicrobial Activities ◽

Functional Theory ◽

1H And 13C Nmr ◽

Combined Use ◽

Computational Testing ◽

Td Dft ◽

Sulfur Containing ◽

Structural Definition

Arsenicin A (C3H6As4O3) was isolated from the New Caledonian poecilosclerid sponge Echinochalina bargibanti, and described as the first natural organic polyarsenic compound. Further bioguided fractionation of the extracts of this sponge led us to isolate the first sulfur-containing organic polyarsenicals ever found in Nature. These metabolites, called arsenicin B and arsenicin C, are built on a noradamantane-type framework that is characterized by an unusual As–As bonding. Extensive NMR measurements, in combination with mass spectra, enabled the assignment of the structure for arsenicin B (C3H6As4S2) as 2. The scarcity of arsenicin C and its intrinsic chemical instability only allowed the collection of partial spectral data, which prevented the full structural definition. After the extensive computational testing of several putative structures, structure 3 was inferred for arsenicin C (C3H6As4OS) by comparing the experimental and density functional theory (DFT)-calculated 1H and 13C NMR spectra. Finally, the absolute configurations of 2 and 3 were determined with a combined use of experimental and time-dependent (TD)-DFT calculated electronic circular dichroism (ECD) spectra and observed specific rotations. These findings pose great challenges for the investigation of the biosynthesis of these metabolites and the cycle of arsenic in Nature. Arsenicins B and C showed strong antimicrobial activities, especially against S. aureus, which is comparable to the reference compound gentamycin.

Download Full-text

Identification and Heterologous Expression of the Biosynthetic Gene Cluster Encoding the Lasso Peptide Humidimycin, a Caspofungin Activity Potentiator

Antibiotics ◽

10.3390/antibiotics9020067 ◽

2020 ◽

Vol 9 (2) ◽

pp. 67 ◽

Cited By ~ 2

Author(s):

Marina Sánchez-Hidalgo ◽

Jesús Martín ◽

Olga Genilloud

Keyword(s):

Cell Wall ◽

Gene Cluster ◽

Genome Mining ◽

Biosynthetic Gene Cluster ◽

Antimicrobial Activities ◽

Biosynthetic Gene ◽

Fungal Cell ◽

Gibson Assembly ◽

Gram Positive Bacteria ◽

Anti Hiv

Humidimycin (MDN-0010) is a ribosomally synthesized and post-translationally modified peptide (RiPP) belonging to class I lasso peptides, and is structurally related to siamycins, which have been shown to have strong antimicrobial activities against Gram-positive bacteria and to possess anti-HIV activity. Humidimycin was isolated from the strain Streptomyces humidus CA-100629, and was shown to synergize the activity of the fungal cell wall inhibitor caspofungin. In this work, the biosynthetic gene cluster of humidimycin was identified by genome mining of S. humidus CA-100629, cloned by Gibson assembly, and heterologously expressed.

Download Full-text

Genome Mining of Marine-Derived Streptomyces sp. SCSIO 40010 Leads to Cytotoxic New Polycyclic Tetramate Macrolactams

Marine Drugs ◽

10.3390/md17120663 ◽

2019 ◽

Vol 17 (12) ◽

pp. 663 ◽

Cited By ~ 4

Author(s):

Wei Liu ◽

Wenjun Zhang ◽

Hongbo Jin ◽

Qingbo Zhang ◽

Yuchan Chen ◽

...

Keyword(s):

Gene Cluster ◽

Genome Mining ◽

Biosynthetic Gene Cluster ◽

Biosynthetic Gene ◽

Trans Orientation ◽

Streptomyces Species ◽

Streptomyces Sp ◽

Isolation And Characterization ◽

Planar Structures ◽

Ic50 Values

Polycyclic tetramate macrolactams (PTMs) biosynthetic gene cluster are widely distributed in different bacterial types, especially in Streptomyces species. The mining of the genomic data of marine-derived Streptomyces sp. SCSIO 40010 reveals the presence of a putative PTM-encoding biosynthetic gene cluster (ptm′ BGC) that features a genetic organization for potentially producing 5/5/6 type of carbocyclic ring-containing PTMs. A fermentation of Streptomyces sp. SCSIO 40010 led to the isolation and characterization of six new PTMs 1–6. Comprehensive spectroscopic analysis assigned their planar structures and relative configurations, and their absolute configurations were deduced by comparing the experimental electronic circular dichroism (ECD) spectra with the reported spectra of the known PTMs. Intriguingly, compounds 1–6 were determined to have a trans-orientation of H-10/H-11 at the first 5-membered ring, being distinct from the cis-orientation in their known PTM congeners. PTMs 1–5 displayed cytotoxicity against several cancer cell lines, with IC50 values that ranged from 2.47 to 17.68 µM.

Download Full-text

Novel Antimicrobial Peptides Derived from Flatfish Genes

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.47.8.2464-2470.2003 ◽

2003 ◽

Vol 47 (8) ◽

pp. 2464-2470 ◽

Cited By ~ 67

Author(s):

Aleksander Patrzykat ◽

Jeffrey W. Gallant ◽

Jung-Kil Seo ◽

Jennifer Pytyck ◽

Susan E. Douglas

Keyword(s):

Antimicrobial Peptides ◽

Antimicrobial Activities ◽

Resistant Organism ◽

Gram Negative Bacteria ◽

Genomic Information ◽

Carboxy Terminus ◽

Antibiotic Resistant ◽

Active Peptides ◽

Flanking Sequences ◽

Flanking Regions

ABSTRACT We report on the identification of active novel antimicrobials determined by screening both the genomic information and the mRNA transcripts from a number of different flatfish for sequences encoding antimicrobial peptides, predicting the sequences of active peptides from the genetic information, producing the predicted peptides chemically, and testing them for their activities. We amplified 35 sequences from various species of flatfish using primers whose sequences are based on conserved flanking regions of a known antimicrobial peptide from winter flounder, pleurocidin. We analyzed the sequences of the amplified products and predicted which sequences were likely to encode functional antimicrobial peptides on the basis of charge, hydrophobicity, relation to flanking sequences, and similarity to known active peptides. Twenty peptides were then produced synthetically and tested for their activities against gram-positive and gram-negative bacteria and the yeast Candida albicans. The most active peptide (with the carboxy-terminus amidated sequence GWRTLLKKAEVKTVGKLALKHYL, derived from American plaice) showed inhibitory activity over a concentration range of 1 to 8 μg/ml against a test panel of pathogens, including the intrinsically antibiotic-resistant organism Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and C. albicans. The methods described here will be useful for the identification of novel peptides with good antimicrobial activities.

Download Full-text

Synthesis, Density Functional Theory (DFT), Urease Inhibition and Antimicrobial Activities of 5-Aryl Thiophenes Bearing Sulphonylacetamide Moieties

Molecules ◽

10.3390/molecules201119661 ◽

2015 ◽

Vol 20 (11) ◽

pp. 19914-19928 ◽

Cited By ~ 11

Author(s):

Mnaza Noreen ◽

Nasir Rasool ◽

Yasmeen Gull ◽

Muhammad Zubair ◽

Tariq Mahmood ◽

...

Keyword(s):

Density Functional Theory ◽

Density Functional ◽

Antimicrobial Activities ◽

Urease Inhibition ◽

Functional Theory

Download Full-text

COX Inhibitory and Cytotoxic Naphthoketal-Bearing Polyketides from Sparticola junci

International Journal of Molecular Sciences ◽

10.3390/ijms222212379 ◽

2021 ◽

Vol 22 (22) ◽

pp. 12379

Author(s):

Katherine Yasmin M. Garcia ◽

Mark Tristan J. Quimque ◽

Gian Primahana ◽

Andreas Ratzenböck ◽

Mark Joseph B. Cano ◽

...

Keyword(s):

Density Functional ◽

Antimicrobial Activities ◽

Mouse Fibroblast ◽

Myelogenous Leukemia ◽

Functional Theory ◽

Docking Analysis ◽

Tddft Calculations ◽

Cox 2 ◽

K 562 Cells ◽

Cox 1

Axenic fermentation on solid rice of the saprobic fungus Sparticola junci afforded two new highly oxidized naphthalenoid polyketide derivatives, sparticatechol A (1) and sparticolin H (2) along with sparticolin A (3). The structures of 1 and 2 were elucidated on the basis of their NMR and HR-ESIMS spectroscopic data. Assignment of absolute configurations was performed using electronic circular dichroism (ECD) experiments and Time-Dependent Density Functional Theory (TDDFT) calculations. Compounds 1–3 were evaluated for COX inhibitory, antiproliferative, cytotoxic and antimicrobial activities. Compounds 1 and 2 exhibited strong inhibitory activities against COX-1 and COX-2. Molecular docking analysis of 1 conferred favorable binding against COX-2. Sparticolin H (2) and A (3) showed a moderate antiproliferative effect against myelogenous leukemia K-562 cells and weak cytotoxicity against HeLa and mouse fibroblast cells.

Download Full-text

Doping effects on the geometric and electronic structure of tin clusters

Physical Chemistry Chemical Physics ◽

10.1039/c9cp05124d ◽

2019 ◽

Vol 21 (44) ◽

pp. 24478-24488 ◽

Cited By ~ 1

Author(s):

Martin Gleditzsch ◽

Marc Jäger ◽

Lukáš F. Pašteka ◽

Armin Shayeghi ◽

Rolf Schäfer

Keyword(s):

Density Functional Theory ◽

Electronic Structure ◽

Density Functional ◽

Beam Deflection ◽

Functional Theory ◽

Doping Effects ◽

Depth Analysis ◽

Trajectory Simulations

In depth analysis of doping effects on the geometric and electronic structure of tin clusters via electric beam deflection, numerical trajectory simulations and density functional theory.

Download Full-text