title: Insights into the biosynthesis of hormaomycin, an exceptionally complex bacterial signaling metabolite.
abstract: Hormaomycin produced by Streptomyces griseoflavus is a structurally highly modified depsipeptide that contains several unique building blocks with cyclopropyl, nitro, and chlorine moieties. Within the genus Streptomyces, it acts as a bacterial hormone that induces morphological differentiation and the production of bioactive secondary metabolites. In addition, hormaomycin is an extremely potent narrow-spectrum antibiotic. In this study, we shed light on hormaomycin biosynthesis by a combination of feeding studies, isolation of the biosynthetic nonribosomal peptide synthetase (NRPS) gene cluster, and in vivo and in vitro functional analysis of enzymes. In addition, several nonnatural hormaomycin congeners were generated by feeding-induced metabolic rerouting. The NRPS contains numerous highly repetitive regions that suggest an evolutionary scenario for this unusual bacterial hormone, providing new opportunities for evolution-inspired metabolic engineering of novel nonribosomal peptides.
authors: Department of Bioorganic Chemistry, Max Planck Institute for Chemical Ecology, 07745 Jena, Germany.
authors: Ivonne
authors: I
authors: Höfer
authors: Max
authors: M
authors: Crüsemann
authors: Markus
authors: M
authors: Radzom
authors: Bernadette
authors: B
authors: Geers
authors: Daniel
authors: D
authors: Flachshaar
authors: Xiaofeng
authors: X
authors: Cai
authors: Axel
authors: A
authors: Zeeck
authors: Jörn
authors: J
authors: Piel
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D055162:Biocatalysis; D047630:Depsipeptides / Q000096:biosynthesis* / Q000737:chemistry; D005810:Multigene Family; D046908:Peptide Biosynthesis, Nucleic Acid-Independent; D010453:Peptide Synthases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics; D010456:Peptides, Cyclic
chemical_list: D001426:Bacterial Proteins; D047630:Depsipeptides; D010453:Peptide Synthases; C510371:hormaomycin; D010456:Peptides, Cyclic; C104385:non-ribosomal peptide synthase