Search results for "A40926"
showing 6 items of 6 documents
Complex Regulatory Networks Governing Production of the Glycopeptide A40926
2018
Glycopeptides (GPAs) are an important class of antibiotics, with vancomycin and teicoplanin being used in the last 40 years as drugs of last resort to treat infections caused by Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus. A few new GPAs have since reached the market. One of them is dalbavancin, a derivative of A40926 produced by the actinomycete Nonomuraea sp. ATCC 39727, recently classified as N. gerenzanensis. This review summarizes what we currently know on the multilevel regulatory processes governing production of the glycopeptide A40926 and the different approaches used to increase antibiotic yields. Some nutrients, e.g., valine, l-glutamine and mal…
A Two-Component regulatory system with opposite effects on glycopeptide antibiotic biosynthesis and resistance
2020
AbstractThe glycopeptide A40926, produced by the actinomycete Nonomuraea gerenzanensis, is the precursor of dalbavancin, a second-generation glycopeptide antibiotic approved for clinical use in the USA and Europe in 2014 and 2015, respectively. The final product of the biosynthetic pathway is an O-acetylated form of A40926 (acA40926). Glycopeptide biosynthesis in N. gerenzanensis is dependent upon the dbv gene cluster that encodes, in addition to the two essential positive regulators Dbv3 and Dbv4, the putative members of a two-component signal transduction system, specifically the response regulator Dbv6 and the sensor kinase Dbv22. The aim of this work was to assign a role to these two ge…
Expression in Streptomyces lividans of Nonomuraea genes cloned in an artificial chromosome
2004
A bacterial artificial chromosomal library of Nonomuraea sp. ATCC39727 was constructed using Escherichia coli-Streptomyces artificial chromosome (ESAC) and screened for the presence of dbv genes known to be involved in the biosynthesis of the glycopeptide A40926. dbv genes were cloned as two large, partially overlapping, fragments and transferred into the host Streptomyces lividans, thus generating strains S. lividansColon, two colonsNmESAC50 and S. lividansColon, two colonsNmESAC57. The heterologous expression of Nonomuraea genes in S. lividans was successfully demonstrated by using combined RT-PCR and proteomic approaches. MALDI-TOF analysis revealed that a Nonomuraea ABC transporter is e…
Phosphate-controlled regulator for the biosynthesis of the dalbavancin precursor A40926
2007
ABSTRACT The actinomycete Nonomuraea sp. strain ATCC 39727 produces the glycopeptide A40926, the precursor of the novel antibiotic dalbavancin. Previous studies have shown that phosphate limitation results in enhanced A40926 production. The A40926 biosynthetic gene ( dbv ) cluster, which consists of 37 genes, encodes two putative regulators, Dbv3 and Dbv4, as well as the response regulator (Dbv6) and the sensor-kinase (Dbv22) of a putative two-component system. Reverse transcription-PCR (RT-PCR) and real-time RT-PCR analysis revealed that the dbv14 - dbv8 and the dbv30 - dbv35 operons, as well as dbv4 , were negatively influenced by phosphate. Dbv4 shows a putative helix-turn-helix DNA-bind…
Two master switch regulators trigger A40926 biosynthesis in Nonomuraea sp. strain ATCC 39727
2015
ABSTRACT The actinomycete Nonomuraea sp. strain ATCC 39727 produces the glycopeptide A40926, the precursor of dalbavancin. Biosynthesis of A40926 is encoded by the dbv gene cluster, which contains 37 protein-coding sequences that participate in antibiotic biosynthesis, regulation, immunity, and export. In addition to the positive regulatory protein Dbv4, the A40926-biosynthetic gene cluster encodes two additional putative regulators, Dbv3 and Dbv6. Independent mutations in these genes, combined with bioassays and liquid chromatography-mass spectrometry (LC-MS) analyses, demonstrated that Dbv3 and Dbv4 are both required for antibiotic production, while inactivation of dbv6 had no effect. In …
Regulation of physiological differentiation in Nonomuraea sp. ATCC 39727
2014
The Actinomycete Nonomuraea produces the glycopeptide A40926, precursor of dalbavancin, a novel lipoglycopeptide homologous to vancomycin that could be used against emerging resistant Gram-positive bacteria. The A40926 biosynthetic gene cluster (dbv), which consists of 37 genes, encodes two regulators, Dbv3 (LuxR-like) and Dbv4 (StrR-like), as well as the response regulator (Dbv6) and the sensor-kinase (Dbv22) of a putative two-component system. Previous work demonstrated a positive role of Dbv4 in antibiotic production by activating the transcription of 13 dbv genes; up to now no role was assigned to Dbv3, Dbv6 and Dbv22. In addition, an IclR-like protein is thought to be involved in dbv4 …