11 research outputs found
1145-118 Torasemide inhibits transcardiac extraction of aldosterone in patients with congestive heart failure
Serum Level of Uric Acid, Partly Secreted From the Failing Heart, is a Prognostic Marker in Patients With Congestive Heart Failure
1145-118 Torasemide inhibits transcardiac extraction of aldosterone in patients with congestive heart failure
1031-134 Relationship between the transcardiac increase of plasma heart-type fatty acid-binding protein and left ventricular remodeling in patients with dilated cardiomyopathy
tRNA-Dependent Aminoacylation of an Amino Sugar Intermediate in the Biosynthesis of a Streptothricin-Related Antibiotic
Relationship Between Renal Function and Plasma Brain Natriuretic Peptide in Patients With Heart Failure
Segmented Assimilation, Transnationalism, and Educational Attainment of Brazilian Migrant Children in Japan
A peptide ligase and the ribosome cooperate to synthesize the peptide pheganomycin
Peptide antibiotics are typically biosynthesized by one of two distinct machineries in a ribosome-dependent or ribosome-independent manner. Pheganomycin (PGM (1)) and related analogs consist of the nonproteinogenic amino acid (S)-2-(3,5-dihydroxy-4-hydroxymethyl)phenyl-2-guanidinoacetic acid (2) and a proteinogenic core peptide, making their origin uncertain. We report the identification of the biosynthetic gene cluster from Streptomyces cirratus responsible for PGM production. Unexpectedly, the cluster contains a gene encoding multiple precursor peptides along with several genes plausibly encoding enzymes for the synthesis of amino acid 2. We identified PGM1, which has an ATP-grasp domain, as potentially capable of linking the precursor peptides with 2, and validate this hypothesis using deletion mutants and in vitro reconstitution. We document PGM1's substrate permissivity, which could be rationalized by a large binding pocket as confirmed via structural and mutagenesis experiments. This is to our knowledge the first example of cooperative peptide synthesis achieved by ribosomes and peptide ligases using a peptide nucleophile