Ag ene cluster encoding ac ryptic trans-acyl transferase polyketide synthase (PKS) was identified in the genomes of Burkholderia gladioli BCC0238 and BCC1622, both isolated from the lungs of cystic fibrosis patients.Bioinfomatics analyses indicated the PKS assembles an ovel member of the glutarimide class of antibiotics,h itherto only isolated from Streptomyces species.S creening of ar ange of growth parameters led to the identification of gladiostatin, the metabolic product of the PKS.NMR spectroscopic analysis revealed that gladiostatin, which has promising activity against several human cancer cell lines and inhibits tumor cell migration, contains an unusual 2-acyl-4-hydroxy-3-methylbutenolide in addition to the glutarimide pharmacophore.A nA fsA-like domain at the C-terminus of the PKS was shown to catalyze condensation of 3-ketothioesters with dihydroxyacetone phosphate,t hus indicating it playsakey role in polyketide chain release and butenolide formation.
Tw oBurkholderia gladioli strains isolated from the lungs of cystic fibrosis patients were found to produce unusual lipodepsipeptides containing aunique citrate-derived fatty acid and ar are dehydro-b-alanine residue.T he gene cluster responsible for their biosynthesis was identified by bioinformatics and insertional mutagenesis.I n-frame deletions and enzyme activity assays were used to investigate the functions of several proteins encoded by the biosynthetic gene cluster,which was found in the genomes of about 45 %ofB.gladioli isolates, suggesting that its metabolic products playanimportant role in the growth and/or survival of the species.T he Chrome Azurol Sa ssayi ndicated that these metabolites bind ferric iron, whichs uppresses their production when added to the growth medium. Moreover,agene encoding aTonB-dependent ferric-siderophore receptor is adjacent to the biosynthetic genes,s uggesting that these metabolites mayf unction as siderophores in B. gladioli.
Tw oBurkholderia gladioli strains isolated from the lungs of cystic fibrosis patients were found to produce unusual lipodepsipeptides containing aunique citrate-derived fatty acid and ar are dehydro-b-alanine residue.T he gene cluster responsible for their biosynthesis was identified by bioinformatics and insertional mutagenesis.I n-frame deletions and enzyme activity assays were used to investigate the functions of several proteins encoded by the biosynthetic gene cluster,which was found in the genomes of about 45 %ofB.gladioli isolates, suggesting that its metabolic products playanimportant role in the growth and/or survival of the species.T he Chrome Azurol Sa ssayi ndicated that these metabolites bind ferric iron, whichs uppresses their production when added to the growth medium. Moreover,agene encoding aTonB-dependent ferric-siderophore receptor is adjacent to the biosynthetic genes,s uggesting that these metabolites mayf unction as siderophores in B. gladioli.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.