Genome-Led Discovery of the Antibacterial Cyclic Lipopeptide Kutzneridine A and Its Silent Biosynthetic Gene Cluster from Species.

Genome analysis of sp. CA-103260 revealed a putative lipopeptide-encoding biosynthetic gene cluster (BGC) that was cloned into a bacterial artificial chromosome (BAC) and heterologously expressed in M1152. As a result, a novel cyclic lipo-tetrapeptide containing two diaminopropionic acid residues and an exotic ,-acetonide ring, kutzneridine A (), was isolated and structurally characterized.

Dilarmycins A-C, Calcium-Dependent Lipopeptide Antibiotics with a Non-canonical Ca-Binding Motif.

Genome analysis of strain sp. CA-278952 revealed a biosynthetic gene cluster encoding a putative lipopeptide with a sequence containing an Asp-Gly-Glu-Ala motif. We envisioned that this motif could mimic the canonical Asp-X-Asp-Gly sequence found in previously reported calcium-dependent lipopeptide antibiotics.

Madurastatins with Imidazolidinone Rings: Natural Products or Side-Reaction Products from Extraction Solvents?

Madurastatins are a group of pentapeptides containing an oxazoline moiety, and, in a few cases, an imidazolidinone ring as an additional structural feature. In our search for new potential antiparasitic metabolites from natural sources, we studied the acetone extracts from a culture of sp. CA-135719.

New Phocoenamicin and Maklamicin Analogues from Cultures of Three Marine-Derived Strains.

Antimicrobial resistance can be considered a hidden global pandemic and research must be reinforced for the discovery of new antibiotics. The spirotetronate class of polyketides, with more than 100 bioactive compounds described to date, has recently grown with the discovery of phocoenamicins, compounds displaying different antibiotic activities. Three marine strains (CA-214671, CA-214658 and CA-218877), identified as phocoenamicins producers, were chosen to scale up their production and LC/HRMS analyses proved that EtOAc extracts from their culture broths produce several structurally related compounds not disclosed before.

Crossiellidines A-F, Unprecedented Pyrazine-Alkylguanidine Metabolites with Broad-Spectrum Antibacterial Activity from sp.

Crosiellidines are intriguing pyrazine-alkylguanidine metabolites isolated from the minor actinomycete genus . Their structures present an unprecedented 2-methoxy-3,5,6-trialkyl pyrazine scaffold and uncommon guanidine prenylations, including an exotic -prenylated -hydroxyguanidine moiety. The novel substitution pattern of the 2-methoxypyrazine core inaugurates a new class of naturally occurring pyrazine compounds, the biosynthetic implications of which are discussed herein.

Identification and heterologous expression of the globomycin biosynthetic gene cluster.

Globomycin is a cyclic lipodepsipeptide originally isolated from several species which displays strong and selective antibacterial activity against Gram-negative pathogens. Its mode of action is based on the competitive inhibition of the lipoprotein signal peptidase II (LspA), which is absent in eukaryotes and considered an attractive target for the development of new antibiotics. Despite its interesting biological properties, the gene cluster encoding its biosynthesis has not yet been identified.

Complete Genome Sequence Analysis of sp. CA-293567 and Identification of the Kribbellichelins A & B and Sandramycin Biosynthetic Gene Clusters.

Minor genera actinomycetes are considered a promising source of new secondary metabolites. The strain sp. CA-293567 produces sandramycin and kribbellichelins A & B In this work, we describe the complete genome sequencing of this strain and the in silico identification of biosynthetic gene clusters (BGCs), focusing on the pathways encoding sandramycin and kribbellichelins A-B.

Exploring as Phocoenamicins Producers.

Over the past few years, new technological and scientific advances have reinforced the field of natural product discovery. The spirotetronate class of natural products has recently grown with the discovery of phocoenamicins, natural actinomycete derived compounds that possess different antibiotic activities. Exploring the MEDINA's strain collection, 27 actinomycete strains, including three marine-derived and 24 terrestrial strains, were identified as possible phocoenamicins producers and their taxonomic identification by 16S rDNA sequencing showed that they all belong to the genus.

Identification of the Biosynthetic Gene Cluster for Pyracrimycin A, an Antibiotic Produced by sp.

Actinomycetes make a wealth of complex, structurally diverse natural products, and a key challenge is to link them to their biosynthetic gene clusters and delineate the reactions catalyzed by each of the enzymes. Here, we report the biosynthetic gene cluster for pyracrimycin A, a set of nine genes that includes a core nonribosomal peptide synthase () that utilizes serine and proline as precursors and a monooxygenase () that catalyzes Baeyer-Villiger oxidation. The cluster is similar to the one for brabantamide A; however, pyracrimycin A biosynthesis differs in that feeding experiments with isotope-labeled serine and proline suggest that a ring opening reaction takes place and a carbon is lost from serine downstream of the oxidation reaction.

Activation and Identification of a Griseusin Cluster in sp. CA-256286 by Employing Transcriptional Regulators and Multi-Omics Methods.

are well-known producers of a range of different secondary metabolites, including antibiotics and other bioactive compounds. Recently, it has been demonstrated that "silent" biosynthetic gene clusters (BGCs) can be activated by heterologously expressing transcriptional regulators from other BGCs. Here, we have activated a silent BGC in sp.

Complete Genome Sequence of sp. CA-230715, Encoding a 35-Module Type I Polyketide Synthase.

We report the sequencing, assembly, and annotation of the genome of sp. CA-230715, a potentially interesting producer of natural products. The genome of CA-230715 was sequenced using PacBio, Illumina, and Nanopore technologies.

Complete Genome Sequence of the Rare Actinobacterium sp. Strain CA-103260.

Here, we report the sequencing, assembly, and annotation of the genome of the rare actinobacterium sp. strain CA-103260. The genome of CA-103260 was sequenced using PacBio and Illumina technologies and it consists of a circular 11,609,901-bp chromosome.

Discovery and Characterization of Epemicins A and B, New 30-Membered Macrolides from sp. CA-103260.

Actinobacteria have been a rich source of novel, structurally complex natural products for many decades. Although the largest genus is , from which the majority of antibiotics in current and past clinical use were originally isolated, other less common genera also have the potential to produce a wealth of novel secondary metabolites. One example is the genus, which currently contains only five reported species.

Complete Genome Sequence of sp. Strain CA-256286.

Here, we report the sequencing, assembly, and annotation of the genome of sp. strain CA-256286. The genome consists of a linear 7,726,360-nucleotide chromosome and a linear 466,817-nucleotide putative plasmid.

Krisynomycins, Imipenem Potentiators against Methicillin-Resistant , Produced by .

A reinvestigation of the acetone extract of the strain CA-091830 of , producer of the imipenem potentiator krisynomycin, resulted in the isolation of two additional analogues, krisynomycins B () and C (), with different chlorination patterns. Genome sequencing of the strain followed by detailed bioinformatics analysis led to the identification of the corresponding biosynthetic gene cluster (BGC) of this cyclic nonribosomal peptide family. The planar structure of the new molecules was determined using HRMS, ESI-qTOF-MS/MS, and 1D and 2D NMR data.

Identification, Cloning and Heterologous Expression of the Gene Cluster Directing RES-701-3, -4 Lasso Peptides Biosynthesis from a Marine Strain.

RES-701-3 and RES-701-4 are two class II lasso peptides originally identified in the fermentation broth of sp. RE-896, which have been described as selective endothelin type B receptor antagonists. These two lasso peptides only differ in the identity of the C-terminal residue (tryptophan in RES-701-3, 7-hydroxy-tryptophan in RES-701-4), thus raising an intriguing question about the mechanism behind the modification of the tryptophan residue.

New Napyradiomycin Analogues from sp. Strain CA-271078.

As part of our continuing efforts to discover new bioactive compounds from microbial sources, a reinvestigation of extracts of scaled-up cultures of the marine-derived sp. strain CA-271078 resulted in the isolation and structural elucidation of four new napyradiomycins (-, ). The known napyradiomycin SC (), whose structural details had not been previously described in detail, and another ten related known compounds (-).

Caniferolide A, a Macrolide from Streptomyces caniferus, Attenuates Neuroinflammation, Oxidative Stress, Amyloid-Beta, and Tau Pathology in Vitro.

The macrolide caniferolide A was isolated from extracts of a culture of the marine-derived actinomycete Streptomyces caniferus, and its ability to ameliorate Alzheimer's disease (AD) hallmarks was determined. The compound reduced neuroinflammatory markers in BV2 microglial cells activated with lipopolysaccharide (LPS), being able to block NFκB-p65 translocation to the nucleus and to activate the Nrf2 pathway. It also produced a decrease in pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), reactive oxygen species (ROS) and nitric oxide release and inhibited iNOS, JNK, and p38 activities.

Structure elucidation and biosynthetic gene cluster analysis of caniferolides A-D, new bioactive 36-membered macrolides from the marine-derived Streptomyces caniferus CA-271066.

Bioassay-guided isolation based on the antifungal activity of a culture broth of the marine-derived actinomycete Streptomyces caniferus CA-271066 led to the discovery of new 36-membered polyol macrolides, caniferolides A-D (1-4). Their connectivity was determined by spectroscopic methods including ESITOF-MS and 1D/2D NMR. The relative stereochemistry of each stereocluster in these compounds was established using NOE analysis, the universal database method and J-based configuration analysis, further assisted by comparisons with NMR data of structurally related macrolides.

Streptocyclinones A and B ameliorate Alzheimer's disease pathological processes in vitro.

Alzheimer's disease (AD) is a pathology characterized by the abnormal accumulation of amyloid-beta (Aβ) and hyperphosphorylated tau. Oxidative stress and neuroinflammation are also strongly related to this disease. The ability of two new glycosylated angucyclinones, streptocyclinones A and B (1 and 2), isolated from Streptomyces sp to improve AD hallmarks was evaluated.

Phocoenamicins B and C, New Antibacterial Spirotetronates Isolated from a Marine Micromonospora sp.

Phocoenamicins B and C ( and ), together with the known spirotetronate phocoenamicin (), were isolated from cultures of sp. The acetone extract from a culture of this strain, isolated from marine sediments collected in the Canary Islands, displayed activity against methicillin-resistant (MRSA), H37Ra and . Bioassay-guided fractionation of this extract using SP207ss column chromatography and preparative reversed-phased HPLC led to the isolation of the new compounds and belonging to the spirotetronate class of polyketides.

MDN-0171, a new medermycin analogue from Streptomyces albolongus CA-186053.

A new medermycin derivative, MDN-0171 (1), and two known structurally related compounds, medermycin (2) and antibiotic G15-F (3) were isolated from the acetone extract of culture broths of the marine-derived Streptomyces albolongus strain CA-186053. Their structures were determined using a combination of spectroscopic techniques, including 1D and 2D NMR and electrospray-time of flight mass spectrometry (ESI-TOF MS). Compounds 2 and 3 accounted for the antimicrobial activity (against methicillin-resistant Staphylococcus aureus and Escherichia coli) previously detected in the crude extract of this actinomycete.

MDN-0170, a New Napyradiomycin from Streptomyces sp. Strain CA-271078.

A new napyradiomycin, MDN-0170 (), was isolated from the culture broth of the marine-derived actinomycete strain CA-271078, together with three known related compounds identified as 4-dehydro-4a-dechloronapyradiomycin A1 (), napyradiomycin A1 () and 3-chloro-6,8-dihydroxy-8-α-lapachone (). The structure of the new compound was determined using a combination of spectroscopic techniques, including 1D and 2D NMR and electrospray-time of flight mass spectrometry (ESI-TOF MS). The relative configuration of compound which contains two independent stereoclusters, has been established by molecular modelling in combination with nOe and coupling constant analyses.

New ikarugamycin derivatives with antifungal and antibacterial properties from Streptomyces zhaozhouensis.

A bioassay guided fractionation of the ethyl acetate extract from culture broths of the strain Streptomyces zhaozhouensis CA-185989 led to the isolation of three new polycyclic tetramic acid macrolactams (1-3) and four known compounds. All the new compounds were structurally related to the known Streptomyces metabolite ikarugamycin (4). Their structural elucidation was accomplished using a combination of electrospray-time of flight mass spectrometry (ESI-TOF MS) and 1D and 2D NMR analyses.

Antimicrobial activity of heterotrophic bacterial communities from the marine sponge Erylus discophorus (Astrophorida, Geodiidae).

Heterotrophic bacteria associated with two specimens of the marine sponge Erylus discophorus were screened for their capacity to produce bioactive compounds against a panel of human pathogens (Staphylococcus aureus wild type and methicillin-resistant S. aureus (MRSA), Bacillus subtilis, Pseudomonas aeruginosa, Acinetobacter baumanii, Candida albicans and Aspergillus fumigatus), fish pathogen (Aliivibrio fischeri) and environmentally relevant bacteria (Vibrio harveyi). The sponges were collected in Berlengas Islands, Portugal.