title: Paenilamicin: structure and biosynthesis of a hybrid nonribosomal peptide/polyketide antibiotic from the bee pathogen Paenibacillus larvae.
abstract: The spore-forming bacterium Paenibacillus larvae is the causative agent of American Foulbrood (AFB), a fatal disease of honey bees that occurs worldwide. Previously, we identified a complex hybrid nonribosomal peptide/polyketide synthesis (NRPS/PKS) gene cluster in the genome of P. larvae. Herein, we present the isolation and structure elucidation of the antibacterial and antifungal products of this gene cluster, termed paenilamicins. The unique structures of the paenilamicins give deep insight into the underlying complex hybrid NRPS/PKS biosynthetic machinery. Bee larval co-infection assays reveal that the paenilamicins are employed by P. larvae in fighting ecological niche competitors and are not directly involved in killing the bee larvae. Their antibacterial and antifungal activities qualify the paenilamicins as attractive candidates for drug development.
authors: Institut für Chemie, Technische Universität Berlin, 10623 Berlin (Germany) http://www.biochemie.tu-berlin.de.
authors: Sebastian
authors: S
authors: Müller
authors: Eva
authors: E
authors: Garcia-Gonzalez
authors: Andi
authors: A
authors: Mainz
authors: Gillian
authors: G
authors: Hertlein
authors: Nina C
authors: NC
authors: Heid
authors: Eva
authors: E
authors: Mösker
authors: Hans
authors: H
authors: van den Elst
authors: Herman S
authors: HS
authors: Overkleeft
authors: Elke
authors: E
authors: Genersch
authors: Roderich D
authors: RD
authors: Süssmuth
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism*; D001516:Bees / Q000254:growth & development / Q000382:microbiology*; D053898:Biosynthetic Pathways; D005798:Genes, Bacterial; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology / Q000662:veterinary*; D007814:Larva / Q000382:microbiology; D005810:Multigene Family; D056507:Paenibacillus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D061065:Polyketides / Q000737:chemistry / Q000378:metabolism*; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides; D061065:Polyketides; D037521:Virulence Factors
keywords: Paenibacillus larvae; antibacterial agents; nonribosomal peptide synthesis; polyketide synthesis; virulence factors