Complete Genome Assembly of DSM 45807 Allows the Characterization of a Novel Glycopeptide Biosynthetic Gene Cluster.

Background: Glycopeptide antibiotics (GPAs) are a very successful class of clinically relevant antibacterials, used to treat severe infections caused by Gram-positive pathogens, e.g., multidrug resistant and methicillin-resistant staphylococci.

Cross-Talking of Pathway-Specific Regulators in Glycopeptide Antibiotics (Teicoplanin and A40926) Production.

Teicoplanin and A40926 (natural precursor of dalbavancin) are clinically relevant glycopeptide antibiotics (GPAs) produced by NRRL B-16726 and ATCC 39727. Their biosynthetic enzymes are coded within large biosynthetic gene clusters (BGCs), named for teicoplanin and for A40926, whose expression is strictly regulated by pathway-specific transcriptional regulators (PSRs), coded by cluster-situated regulatory genes (CSRGs). Herein, we investigated the "cross-talk" between the CSRGs from and , through the analysis of GPA production levels in and strains, with knockouts of CSRGs cross-complemented by the expression of heterologous CSRGs.

Structural Determinants of the Specific Activities of an L-Amino Acid Oxidase from CPMOR-1 with Broad Substrate Specificity.

The strain CPMOR-1 expresses a flavin adenine dinucleotide (FAD)-dependent L-amino acid oxidase (LAAO) with broad substrate specificity. Steady-state kinetic analysis of its reactivity towards the 20 proteinogenic amino acids showed some activity to all except proline. The relative specific activity for amino acid substrates was not correlated only with or values, since the two parameters often varied independently of each other.

Genomic Insights into the Distribution and Phylogeny of Glycopeptide Resistance Determinants within the Phylum.

The spread of antimicrobial resistance (AMR) creates a challenge for global health security, rendering many previously successful classes of antibiotics useless. Unfortunately, this also includes glycopeptide antibiotics (GPAs), such as vancomycin and teicoplanin, which are currently being considered last-resort drugs. Emerging resistance towards GPAs risks limiting the clinical use of this class of antibiotics-our ultimate line of defense against multidrug-resistant (MDR) Gram-positive pathogens.

Genomic-Led Discovery of a Novel Glycopeptide Antibiotic by DSM 45129.

Glycopeptide antibiotics (GPAs) are last defense line drugs against multidrug-resistant Gram-positive pathogens. Natural GPAs teicoplanin and vancomycin, as well as semisynthetic oritavancin, telavancin, and dalbavancin, are currently approved for clinical use. Although these antibiotics remain efficient, emergence of novel GPA-resistant pathogens is a question of time.

New Molecular Tools for Regulation and Improvement of A40926 Glycopeptide Antibiotic Production in ATCC 39727.

Genome sequencing has revealed that spp. represent a still largely unexplored source of specialized metabolites. ATCC 39727 is the most studied representative species since it produces the glycopeptide antibiotic (GPA) A40926 - the precursor of the clinically relevant antibiotic dalbavancin, approved by the FDA in 2014 for the treatment of acute skin infections caused by multi-drug resistant Gram-positive pathogens.

The L-amino Acid Oxidase with Antimicrobial Activity Is a Flavoenzyme.

The marine environment is a rich source of antimicrobial compounds with promising pharmaceutical and biotechnological applications. The genus harbors one of the highest proportions of bacterial species producing antimicrobial molecules. For decades, the presence of proteins with L-amino acid oxidase (LAAO) and antimicrobial activity in has been known.

Structure and Enzymatic Properties of an Unusual Cysteine Tryptophylquinone-Dependent Glycine Oxidase from Pseudoalteromonas luteoviolacea.

Glycine oxidase from Pseudoalteromonas luteoviolacea (PlGoxA) is a cysteine tryptophylquinone (CTQ)-dependent enzyme. Sequence analysis and phylogenetic analysis place it in a newly designated subgroup (group IID) of a recently identified family of LodA-like proteins, which are predicted to possess CTQ. The crystal structure of PlGoxA reveals that it is a homotetramer.