title: Manipulation of regulatory genes reveals complexity and fidelity in hormaomycin biosynthesis.
abstract: Hormaomycin (HRM) is a structurally remarkable peptide produced by Streptomyces griseoflavus W-384 that acts as a Streptomyces signaling metabolite and exhibits potent antibiotic activity against coryneform actinomycetes. HRM biosynthetic studies have been hampered by inconsistent and low production. To enhance fermentation titers, the role of its cluster-encoded regulatory genes was investigated. Extra copies of the putative regulators hrmA and hrmB were introduced into the wild-type strain, resulting in an increase of HRM production and its analogs up to 135-fold. For the HrmB overproducer, six bioactive analogs were isolated and characterized. This study demonstrates that HrmA and HrmB are positive regulators in HRM biosynthesis. A third gene, hrmH, was identified as encoding a protein capable of shifting the metabolic profile of HRM and its derivatives. Its manipulation resulted in the generation of an additional HRM analog.
authors.affiliation: Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, 53121 Bonn, Germany.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Cai
authors.forename: Roberta
authors.initials: R
authors.lastname: Teta
authors.forename: Christoph
authors.initials: C
authors.lastname: Kohlhaas
authors.forename: Max
authors.initials: M
authors.lastname: Crüsemann
authors.forename: Reiko
authors.initials: R
authors.lastname: Ueoka
authors.forename: Alfonso
authors.initials: A
authors.lastname: Mangoni
authors.forename: Michael F
authors.initials: MF
authors.lastname: Freeman
authors.forename: Jörn
authors.initials: J
authors.lastname: Piel
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology; D001173:Arthrobacter / Q000187:drug effects; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D047630:Depsipeptides / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D005810:Multigene Family; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism; D010456:Peptides, Cyclic
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D047630:Depsipeptides; C510371:hormaomycin; D010456:Peptides, Cyclic