title: Epsilon-poly-L-lysine dispersity is controlled by a highly unusual nonribosomal peptide synthetase.
abstract: Epsilon-Poly-L-lysine (epsilon-PL) consists of 25-35 L-lysine residues in isopeptide linkages and is one of only two amino acid homopolymers known in nature. Elucidating the biosynthetic mechanism of epsilon-PL should open new avenues for creating novel classes of biopolymers. Here we report the purification of an epsilon-PL synthetase (Pls; 130 kDa) and the cloning of its gene from an epsilon-PL-producing strain of Streptomyces albulus. Pls was found to be a membrane protein with adenylation and thiolation domains characteristic of the nonribosomal peptide synthetases (NRPSs). It had no traditional condensation or thioesterase domain; instead, it had six transmembrane domains surrounding three tandem soluble domains. These tandem domains iteratively catalyzed L-lysine polymerization using free L-lysine polymer (or monomer in the initial reaction) as acceptor and Pls-bound L-lysine as donor, directly yielding chains of diverse length. Thus, Pls is a new single-module NRPS having an amino acid ligase-like catalytic activity for peptide bond formation.
authors.affiliation: Yokohama Research Center, Chisso Corporation, 5-1 Ookawa, Kanazawa-Ku, Yokohama 236-8605, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamanaka
authors.forename: Chitose
authors.initials: C
authors.lastname: Maruyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takagi
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Hamano
mesh_terms: D001426:Bacterial Proteins; D002384:Catalysis; D003001:Cloning, Molecular; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D046908:Peptide Biosynthesis, Nucleic Acid-Independent; D010453:Peptide Synthases / Q000378:metabolism*; D011107:Polylysine / Q000096:biosynthesis*; D011487:Protein Conformation; D013302:Streptomyces / Q000201:enzymology*; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; D011107:Polylysine; D010453:Peptide Synthases; C533948:epsilon-poly-L-lysine synthethase, Streptomyces albulus