Lanthipeptide

Streptomyces are prolific producers of secondary metabolites from which many clinically useful compounds have been derived. They inhabit diverse habitats but have rarely been reported in vertebrates. Here, we aim to determine to what extent the ecological source (bat host species and cave sites) influence the genomic and biosynthetic diversity of Streptomyces bacteria. We analysed draft genomes of 132 Streptomyces isolates sampled from 11 species of insectivorous bats from six cave sites in Arizona and New Mexico, USA...

Pyrroloiminoquinone containing natural products have long been known for their biological activities. They are derived from tryptophan, but their biosynthetic pathways have remained elusive. Studies on the biosynthetic gene cluster (BGC) that produces the ammosamides revealed that the first step is attachment of Trp to the C-terminus of a scaffold peptide in an ATP and tRNA dependent manner catalyzed by a PEptide Amino-acyl tRNA ligase (PEARL). The indole of the Trp is then oxidized to a hydroxyquinone. We previously proposed a chemically plausible and streamlined pathway for converting this intermediate to the ammosamides using additional enzymes encoded in the BGC...

The carboxyl-terminal (C-terminal) S-[(Z)-2-aminovinyl]-cysteine (AviCys) analogs have been identified in four families of ribosomally synthesized and post-translationally modified peptides (RiPPs): lanthipeptides, linaridins, thioamitides, and lipolanthines. Within identified biosynthetic pathways, a highly reactive enethiol intermediate, formed through an oxidative decarboxylation catalyzed by a LanD-like flavoprotein, can undergo two types of cyclization: a Michael addition with a dehydroamino acid or a coupling reaction initiated by a radical species...

BACKGROUND: Plant microbiome confers versatile functional roles to enhance survival fitness as well as productivity. In the present study two pearl millet panicle microbiome member species Bacillus subtilis PBs 12 and Bacillus paralicheniformis PBl 36 found to have beneficial traits including plant growth promotion and broad-spectrum antifungal activity towards taxonomically diverse plant pathogens. Understanding the genomes will assist in devising a bioformulation for crop protection while exploiting their beneficial functional roles...

The demands of intensified aquaculture production and escalating disease prevalence underscore the need for efficacious probiotic strategies to enhance fish health. This study focused on isolating and characterising potential probiotics from the gut microbiota of the emerging aquaculture species jade perch (Scortum barcoo). Eighty-seven lactic acid bacteria and 149 other bacteria were isolated from the digestive tract of five adult jade perch. The screening revealed that 24 Enterococcus hirae isolates inhibited the freshwater pathogens Aeromonas sobria and Streptococcus iniae...

The genus Bifidobacterium widely exists in human gut and has been increasingly used as the adjuvant probiotics for the prevention and treatment of diseases. However, the functional differences of Bifidobacterium genomes from different regions of the world remain unclear. We here describe an extensive study on the genomic characteristics and function annotations of 1512 genomes (clustered to 849 non-redundant genomes) of Bifidobacterium cultured from human gut. The distribution of some carbohydrate-active enzymes varied among different Bifidobacterium species and continents...

Myxobacteria have comparatively large genomes that contain many biosynthetic genes with the potential to produce secondary metabolites. Based on genome mining, we discovered a new biosynthetic gene cluster of class III lanthipeptide in the genome of the myxobacterium Melittangium boletus. The biosynthetic gene cluster contained a precursor peptide-coding gene bolA, and a class III lanthipeptide synthetase-coding gene bolKC. The expression vector containing bolA and bolKC was constructed using synthetic DNA with codon-optimized sequences based on the commercially available vector pET29b...

Bacillus clausii is a commercial spore probiotic known to treat multiple diseases. An increased interest in exploring the nutraceutical and probiotic properties of various microorganisms has made researchers explore more about these bacteria. The current trends in the healthcare industry are majorly focused on devising new therapies to avoid drug and pathogen resistance in patients. Antimicrobial peptides have been considered a source of antibiotics for a long time. Still, getting new therapies into the market is a big challenge...

A novel filamentous actinobacterium designated strain 4-36T showing broad-spectrum antifungal activity was isolated from a coal mining site in Mongolia, and its taxonomic position was determined using polyphasic approach. Optimum growth occurred at 30 °C, pH 7.5 and in the absence of NaCl. Aerial and substrate mycelia were abundantly formed on agar media. The colour of aerial mycelium was white and diffusible pigments were not formed. Phylogenetic analyses based on 16S rRNA gene sequence showed that strain 4-36T formed a distinct clade within the genus Amycolatopsis ...

We report the efficient and site selective modification of non-canonical dehydroamino acids in ribosomally synthesized and post-transationally modified peptides (RiPPs) by β-amination. The singly modified thiopeptide Thiostrepton showed an up to 35-fold increase in water solubility, and minimum inhibitory concentration (MIC) assays showed that antimicrobial activity remained good, albeit lower than the unmodified peptide. Also the lanthipeptide nisin could be modified using this method.

Fermented milk products (FMPs) contain probiotics that are live bacteria considered to be beneficial to human health due to the production of various bioactive molecules. In this study, nine artisanal FMPs (kefir, ayran, khurunga, shubat, two cottage cheeses, bryndza, khuruud and suluguni-like cheese) from different regions of Russia were characterized using metagenomics. A metagenomic sequencing of ayran, khurunga, shubat, khuruud and suluguni-like cheese was performed for the first time. The taxonomic profiling of metagenomic reads revealed that Lactococcus species, such as Lc...

A Gram-positive, aerobic, rod-shaped, spore-forming bacterium, designated NE201T , was isolated from a freshwater pond in Village Nerur, India. Growth was observed in the range of 15-45 °C temperature with optimum at 30 °C, pH range of 5-9 (optimum at 7.0), and at concentrations of NaCl ranging between 0 and 14% (optimum 0%, w/v). The 16S rRNA gene sequence showed the highest similarity with Fictibacillus enclensis NIO-1003T (JF893461) at 99.01% followed by F. rigui WPCB074T (EU939689) at 98...

Lanthipeptides make up a large group of natural products that belong to the ribosomally synthesized and post-translationally modified peptides (RiPPs). Lanthipeptides contain lanthionine and methyllanthionine bis-amino acids that have varying stereochemistry. The stereochemistry of new lanthipeptides is often not determined because current methods require equipment that is not standard in most laboratories. In this study, we developed a facile, efficient, and user-friendly method for detecting lanthipeptide stereochemistry, utilizing advanced Marfey's analysis with detection by liquid chromatography coupled with mass spectrometry (LC-MS)...

The myxobacteria are an attractive bioresource for bioactive compounds since the large size genome contains many biosynthetic gene clusters of secondary metabolites. The genome of the myxobacterium Melittangium boletus contains three biosynthetic gene clusters for lanthipeptide production. One of the gene clusters includes genes coding lanthipeptide precursor (melA), class II lanthipeptide synthetase (melM), and transporter (melT). The amino acid sequence of melA indicated similarity with that of known lanthipeptides mersacidin and lichenicidin A1 by the alignment...

Nisin serves as the prototype within the lantibiotic group of antimicrobial peptides, exhibiting a broad-spectrum inhibition against Gram-positive bacteria, including important food-borne pathogens and clinically relevant antibiotic-resistant strains. The gene-encoded nature of nisin allows for gene-based bioengineering, enabling the generation of novel derivatives. It has been demonstrated that nisin mutants can be produced with improved functional properties. Here, we particularly focus on the uncommon amino acid residues dehydroalanine (Dha) and dehydrobutyrin (Dhb), whose functions are not yet fully elucidated...

Streptomyces justiciae WPN32 is an endophytic actinobacterium isolated from the rhizosphere of turmeric field soil at the Botanical Garden of Suranaree University of Technology (Nakhon Ratchasima Province, Thailand). Here we present the draft genome sequence of S. justiciae WPN32. It was sequenced on the Illumina NextSeq 550 sequencer. The draft genome consisted of 123 contigs with a total size of 9,832,147 base pairs, an N50 of 237,572 base pairs and a GC content of 70.87%. The dDDH between WPN32 and Streptomyces justiciae 3R004T was 80...

Genome mining studies have revealed the remarkable combinatorial diversity of ribosomally synthesized and post-translationally modified peptides (RiPPs) in marine bacteria, including prochlorosins. However, mining strategies also prove valuable in investigating the genomic landscape of associated genes within biosynthetic gene cluster (BGC) specific to targeted RiPPs of interest. Our study contributes to the enrichment of knowledge regarding prochlorosin diversity. It offers insights into potential mechanisms involved in their biosynthesis and modification, such as hyper-modification, which may give rise to active lantibiotics...

Addressing the current antibiotic-resistance challenge would be aided by the identification of compounds with novel mechanisms of action. Epilancin 15X, a lantibiotic produced by Staphylococcus epidermidis 15 × 154, displays antimicrobial activity in the submicromolar range against a subset of pathogenic Gram-positive bacteria. S. epidermidis is a common member of the human skin or mucosal microbiota. We here investigated the mechanism of action of epilancin 15X. The compound is bactericidal against Staphylococcus carnosus as well as Bacillus subtilis and appears to kill these bacteria by membrane disruption...

Human-associated bacteria secrete modified peptides to control host physiology and remodel the microbiota species composition. Here we scanned 2,229 Human Microbiome Project genomes of species colonizing skin, gastrointestinal tract, urogenital tract, mouth and trachea for gene clusters encoding RiPPs (ribosomally synthesized and post-translationally modified peptides). We found 218 lanthipeptides and 25 lasso peptides, 70 of which were synthesized and expressed in E. coli and 23 could be purified and functionally characterized...

Cyclic peptides represent a burgeoning area of interest in therapeutic and biotechnological research. In opposition to their linear counterparts, cyclic peptides, such as certain ribosomally synthesized and post-translationally modified peptides (RiPPs), are more conformationally constrained and less susceptible to proteolytic degradation. The lanthipeptide RiPP cytolysin L forms a covalently enforced helical structure that may be used to disrupt helical interactions at protein-protein interfaces. Herein, an expression system is reported to produce lanthipeptides and structurally diverse cytolysin L derivatives in mammalian cells...