title: A Peptidyl-Transesterifying Type I Thioesterase in Salinamide Biosynthesis.
abstract: Salinamide A belongs to a rare class of bicyclic depsipeptide antibiotics in which the installation of a (4-methylhexa-2,4-dienoyl)glycine handle across a hexadepsipeptide core contributes to its chemical complexity and biological properties. Herein, we report the genetic and biochemical basis for salinamide construction in the marine bacterium Streptomyces sp. CNB-091, which involves a novel intermolecular transesterification reaction catalyzed by a type I thioesterase. Heterologous expression studies revealed the central role of the nonribosomal peptide synthetase Sln9 in constructing and installing the distinctive acylglycine "basket handle" of salinamide. Biochemical characterization of the Sln9 thioesterase domain established that transesterification of the serine residue of desmethylsalinamide E with acylated glycyl thioesters yields desmethylsalinamide C.
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92037 (USA) http://scrippsscholars.ucsd.edu/bsmoore.
authors.forename: Lauren
authors.initials: L
authors.lastname: Ray
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92037 (USA) http://scrippsscholars.ucsd.edu/bsmoore.|Yokohama Research Center, JNC Corporation, Yokohama 236-8605 (Japan).
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamanaka
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92037 (USA) http://scrippsscholars.ucsd.edu/bsmoore. bsmoore@ucsd.edu.|Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92037 (USA). bsmoore@ucsd.edu.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Moore
mesh_terms: D047630:Depsipeptides / Q000096:biosynthesis* / Q000737:chemistry; D008968:Molecular Conformation; D010170:Palmitoyl-CoA Hydrolase / Q000737:chemistry / Q000378:metabolism*; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry / Q000378:metabolism
chemical_list: D047630:Depsipeptides; C529014:salinamide A; D010170:Palmitoyl-CoA Hydrolase
keywords: biosynthesis; intermolecular transesterification; peptides; salinamide; thioesterase