Uncovering the biotechnological capacity of marine and brackish water Planctomycetota.

An appealing strategy for finding novel bioactive molecules in Nature consists in exploring underrepresented and -studied microorganisms. Here, we investigated the antimicrobial and tumoral anti-proliferative bioactivities of twenty-three marine and estuarine bacteria of the fascinating phylum Planctomycetota. This was achieved through extraction of compounds produced by the Planctomycetota cultured in oligotrophic medium followed by an antimicrobial screening against ten relevant human pathogens including Gram-positive and Gram-negative bacteria, and fungi.

New Eremophilane-Type Sesquiterpenes from the Marine Sediment-Derived Fungus BC17 and Their Cytotoxic and Antimicrobial Activities.

The fungal strain BC17 was isolated from sediments collected in the intertidal zone of the inner Bay of Cadiz and characterized as . On the basis of the one strain-many compounds (OSMAC) approach, four new eremophilane-type sesquiterpenes (-), together with thirteen known derivatives (-) and two reported diketopiperazines (, ), were isolated from this strain. The chemical structures and absolute configurations of the new compounds were determined through extensive NMR and HRESIMS spectroscopic studies and ECD calculation.

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.

Discovery and Hit-to-Lead Optimization of Benzothiazole Scaffold-Based DNA Gyrase Inhibitors with Potent Activity against and .

We have developed compounds with a promising activity against and , which are both on the WHO priority list of antibiotic-resistant bacteria. Starting from DNA gyrase inhibitor , we identified compound , featuring a 10-fold improved aqueous solubility, a 10-fold improved inhibition of topoisomerase IV from and , a 10-fold decreased inhibition of human topoisomerase IIα, and no cross-resistance to novobiocin. Cocrystal structures of in complex with GyrB24 and ()- in complex with GyrB23 and GyrB24 revealed their binding to the ATP-binding pocket of the GyrB subunit.

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.

Kribbellichelins A and B, Two New Antibiotics from sp. CA-293567 with Activity against Several Human Pathogens.

Current needs in finding new antibiotics against emerging multidrug-resistant superbugs are pushing the scientific community into coming back to Nature for the discovery of novel active structures. Recently, a survey of halophilic actinomyectes from saline substrates of , in the Cúllar-Baza depression (Granada, Spain), led us to the isolation and identification of 108 strains from the rhizosphere of the endemic plant . Evaluation of the potential of these strains to produce new anti-infective agents against superbug pathogens was performed through fermentation in 10 different culture media using an OSMAC approach and assessment of the antibacterial and antifungal properties of their acetone extracts.

Discovery of actinomycin L, a new member of the actinomycin family of antibiotics.

Streptomycetes are major producers of bioactive natural products, including the majority of the naturally produced antibiotics. While much of the low-hanging fruit has been discovered, it is predicted that less than 5% of the chemical space of natural products has been mined. Here, we describe the discovery of the novel actinomycins L and L produced by Streptomyces sp.

Caerulines A and B, Flavonol Diacylglycosides from .

Two undescribed 4'--methylkaempferol-[3″,4″-di--coumaroyl]-α-l-rhamnopyranosides, caerulines A and B (), along with three known 4'--methylkaempferol diacylrhamnosides isomers () were isolated from an ethanol extract of the leaves of , a native plant growing on the Colombian Caribbean coast. The chemical structures of and were elucidated by spectroscopic methods. The effect of compounds against four pathogenic microorganisms [i.

Isolation and characterization of new phenolic siderophores with antimicrobial properties from sp. UIAU-6B.

Five new phenolic siderophores - were isolated from the organic extract of a culture broth in a modified SGG medium of sp. UIAU-6B, obtained from sediments collected from the Oyun river in North Central Nigeria. The structure of the new compounds, pseudomonin A-C (-) and pseudomobactin A and B ( and ) isolated alongside two known compounds, pseudomonine () and salicylic acid (), were elucidated based on high-resolution mass spectrometry, 1D and 2D NMR analyses.

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.

Pentaminomycins F and G, Nonribosomal Peptides Containing 2-Pyridylalanine.

Pentaminomycins F-H (-), a group of three new hydroxyarginine-containing cyclic pentapeptides, were isolated from cultures of a subsp. strain along with the known pentaminomycins A-E. The structures of the new peptides were determined by a combination of mass spectrometry, NMR, and Marfey's analyses.

Taxonomy Driven Discovery of Polyketides from .

Five new polyketides were isolated from the rare filamentous fungus IBT 16748 including calidiol A (); three phthalide derivatives califuranones A, A, and B (-); and a pair of enantiomers (-)-calitetralintriol A (-) and (+)-calitetralintriol A (+) together with four known metabolites (-). The structures of the new products were established by extensive spectroscopic analyses including HRMS and 1D and 2D NMR. The absolute configurations of two diastereomers and and the enantiomers (-) and (+) were assigned by comparing their experimental and calculated ECD data, whereas the absolute configuration of was proposed by analogy.

Oxepinamides L and M, two new oxepine-pyrimidinone-ketopiperazine type nonribosomal peptides from .

A chemical investigation of IBT 16748 led to the isolation of two new oxepine-pyrimidinone-ketopiperazine type nonribosomal peptides oxepinamides L () and M (). Their structures were characterised by spectroscopic analysis including HRESIMS, 1D and 2D NMR. The absolute structure of was assigned by ECD calculation.

New naphthyl derivatives from Aspergillus californicus.

Two new naphthyl-products calinaphthyltriol A (1) and calinaphthalenone A (2) were isolated from Aspergillus californicus IBT 16748 together with one known compound ophiobolin X (3). Their structures were elucidated by extensive spectroscopic analyses. The absolute configuration of 2 was solved by comparing its optical rotation with data for the known compounds 4, 5, and 6 as well as theoretical calculations.

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.

Nephrotic syndrome in the setting of LECT2 amyloidosis: Take a look at the podocyte.

Amyloid light-chain (AL) amyloidosis represents the most common type of amyloid affecting the kidneys. As AL amyloidosis is frequently clinically manifested as nephrotic syndrome, this glomerular syndrome has been improperly linked to all other types of kidney amyloidosis. In this report, we highlight the importance of amyloid typing, as the deposition of several amyloidotic proteins in the kidneys is not associated with heavy proteinuria.

Structural Elucidation of Antibiotic TKR2999, an Antifungal Lipodepsipeptide Isolated from the Fungus .

An antifungal lipodepsipeptide was obtained from cultures of the fungus CF-236885. Its structure, elucidated by HRMS and NMR spectroscopy, contained Gly, Thr, Asn, β-Ala, Orn, Ala, two Ser residues, and 3-hydroxy-4-methylhexadecanoic acid. The absolute configuration of its amino acid residues was determined using Marfey's analysis and -based configuration analysis helped to establish the relative configuration of the 3-hydroxy-4-methylhexadecanoic acid moiety.

Cacaoidin, First Member of the New Lanthidin RiPP Family.

Lantibiotics are ribosomally synthesized and post-translationally modified peptides (RiPPs) characterized by the presence of lanthionine or methyllanthionine rings and their antimicrobial activity. Cacaoidin, a novel glycosylated lantibiotic, was isolated from a Streptomyces cacaoi strain and fully characterized by NMR, mass spectrometry, chemical derivatization approaches and genome analysis. The new molecule combines outstanding structural features, such as a high number of d-amino acids, an uncommon glycosylated tyrosine residue and an unprecedented N,N-dimethyl lanthionine.

-Alkyl Hydroxamates Display Potent and Selective Antileishmanial Activity.

() causes visceral, cutaneous, and mucosal leishmaniasis in humans and canine leishmaniasis in dogs. Herein, we describe that -alkyl hydroxamate derivatives displayed potent and selective activity against the amastigote stage of while no activity was observed against promastigotes. Compound showed potent activity against .

First evidence of anticancer and antimicrobial activity in Mediterranean mesopelagic species.

Mesopelagic organisms form huge biomass aggregations, supporting important pelagic trophic webs and several top predators. Although some studies on the occurrence, biology and ecology of these organisms are available, to date there are no investigations on their potential use for anticancer and antimicrobial biotechnological applications. The aim of this study was to screen extracts of seven mesopelagic species for possible anticancer (Lung cell line A549, skin cell line A2058, liver cell line HepG2, breast cell line MCF7 and pancreas cell line MiaPaca-2) and antibacterial (Gram-negative bacteria Escherichia coli and Klebsiella pneumoniae, the Gram-positive bacteria methicillin resistant/sensitive Staphylococcus aureus, and Mycobacterium tuberculosis) activities.

Diketopiperazines and other bioactive compounds from bacterial symbionts of marine sponges.

Humanity faces great challenges, such as the rise of bacterial antibiotic resistance and cancer incidence. Thus, the discovery of novel therapeutics from underexplored environments, such as marine habitats, is fundamental. In this study, twelve strains from the phylum Firmicutes and thirty-four strains from the phylum Proteobacteria, isolated from marine sponges of the Erylus genus, collected in Portuguese waters, were tested for bioactivities and the secondary metabolites were characterised.

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 (-).

Design of High-Throughput Screening of Natural Extracts to Identify Molecules Bypassing Primary Coenzyme Q Deficiency in .

Coenzyme Q (CoQ) deficiency syndrome is a rare disease included in the family of mitochondrial diseases, which is a heterogeneous group of genetic disorders characterized by defective energy production. CoQ biosynthesis in humans requires at least 11 gene products acting in a multiprotein complex within mitochondria. The high-throughput screening (HTS) method based on the stabilization of the CoQ biosynthesis complex (Q-synthome) produced by the gene overexpression is proven here to be a successful method for identifying new molecules from natural extracts that are able to bypass the CoQ deficiency in yeast mutant cells.

Synthesis of Trichodermin Derivatives and Their Antimicrobial and Cytotoxic Activities.

Trichothecene mycotoxins are recognized as highly bioactive compounds that can be used in the design of new useful bioactive molecules. In , the first specific step in trichothecene biosynthesis is carried out by a terpene cyclase, trichodiene synthase, that catalyzes the conversion of farnesyl diphosphate to trichodiene and is encoded by the gene. Overexpression of resulted in increased levels of trichodermin, a trichothecene-type toxin, which is a valuable tool in preparing new molecules with a trichothecene skeleton.

Amphidinol 22, a New Cytotoxic and Antifungal Amphidinol from the Dinoflagellate .

Due to the unique biodiversity and the physical-chemical properties of their environment, marine microorganisms have evolved defense and signaling compounds that often have no equivalent in terrestrial habitats. The aim of this study was to screen extracts of the dinoflagellate for possible bioactivities (i.e.