Paenilamicin: Structure and Biosynthesis of a Hybrid Nonribosomal Peptide/Polyketide Antibiotic from the Bee Pathogen Paenibacillus larvae

• Published in: Angewandte Chemie (International ed.) Vol. 53; no. 40; pp. 10821 - 10825
• Main Authors: Müller, Sebastian, Garcia-Gonzalez, Eva, Mainz, Andi, Hertlein, Gillian, Heid, Nina C., Mösker, Eva, van den Elst, Hans, Overkleeft, Herman S., Genersch, Elke, Süssmuth, Roderich D.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 26.09.2014; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - metabolism; antibacterial agents; Antiinfectives and antibacterials; Apis mellifera; Bees; Bees - growth & development; Bees - microbiology; Biosynthesis; Biosynthetic Pathways; Chemistry; Chemistry, Multidisciplinary; Clusters; Drugs; Fouling; Genes; Genes, Bacterial; Gram-Positive Bacterial Infections - microbiology; Gram-Positive Bacterial Infections - veterinary; Honey; Larva - microbiology; Larvae; Multigene Family; nonribosomal peptide synthesis; Paenibacillus - chemistry; Paenibacillus - genetics; Paenibacillus - metabolism; Paenibacillus - pathogenicity; Paenibacillus larvae; Peptides; Peptides - chemistry; Peptides - genetics; Peptides - metabolism; Physical Sciences; polyketide synthesis; Polyketides - chemistry; Polyketides - metabolism; Science & Technology; virulence factors; Virulence Factors - chemistry; Virulence Factors - genetics; Virulence Factors - metabolism; polyketide synthesis; nonribosomal peptide synthesis; Paenibacillus larvae; antibacterial agents; virulence factors
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201404572

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. The bee all and end all? American Foulbrood, which is caused by the bacterium Paenibacillus larvae, is a widespread and devastating disease of the honey bee brood. Through the isolation and structure elucidation of the antibacterial and antifungal paenilamicins, a fascinating nonribosomal biosynthesis has been deciphered. The study of the secondary metabolites of P. larvae sheds light on the virulence mechanisms of this serious disease.