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Cadasides, calcium-dependent acidic lipopeptides from the soil metagenome that are active against multidrug resistant bacteria.

07:00 EST 8th February 2019 | BioPortfolio

Summary of "Cadasides, calcium-dependent acidic lipopeptides from the soil metagenome that are active against multidrug resistant bacteria."

The growing threat of antibiotic resistance necessitates the discovery of antibiotics that are active against resistant pathogens. Calcium-dependent antibiotics are a small family of structurally diverse acidic lipopeptides assembled by non-ribosomal peptide synthetases (NRPSs) that are known to display various modes of action against antibiotic-resistant pathogens. Here we use NRPS adenylation (AD) domain sequencing to guide the identification, recovery and cloning of the cde biosynthetic gene cluster from a soil metagenome. Heterologous expression of the cde biosynthetic gene cluster led to the production of cadasides A (1) and B (2), a sub-family of acidic lipopeptides that is distinct from previously characterized calcium-dependent antibiotics in terms of both overall structure and acidic residue rich peptide core. The cadasides inhibit the growth of multidrug-resistant Gram-positive pathogens by disrupting cell wall biosynthesis in the presence of high concentrations of calcium. Interestingly, sequencing of AD domains from diverse soils found that sequences predicted to arise from cadaside-like gene clusters are predominantly found in soils containing high levels of calcium carbonate.

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This article was published in the following journal.

Name: Journal of the American Chemical Society
ISSN: 1520-5126
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Medical and Biotech [MESH] Definitions

A regulatory calcium-calmodulin-dependent protein kinase that specifically phosphorylates CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 1; CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 2; CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 4; and PROTEIN KINASE B. It is a monomeric enzyme that is encoded by at least two different genes.

A monomeric calcium-calmodulin-dependent protein kinase subtype that is primarily expressed in neuronal tissues; T-LYMPHOCYTES and TESTIS. The activity of this enzyme is regulated by its phosphorylation by CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.

A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.

A monomeric calcium-calmodulin-dependent protein kinase subtype that is expressed in a broad variety of mammalian cell types. Its expression is regulated by the action of CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE. Several isoforms of this enzyme subtype are encoded by distinct genes.

Acidic protein found in SARCOPLASMIC RETICULUM that binds calcium to the extent of 700-900 nmoles/mg. It plays the role of sequestering calcium transported to the interior of the intracellular vesicle.

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