title: New aminocoumarins from the rare actinomycete Catenulispora acidiphila DSM 44928: identification, structure elucidation, and heterologous production.
abstract: Genome mining led to the discovery of a novel aminocoumarin gene cluster in the rare actinomycete Catenulispora acidiphila DSM 44928. Sequence analysis revealed the presence of genes putatively involved in export/resistance, regulation, and biosynthesis of the aminocoumarin moiety and its halogenation, as well as several genes with so far unknown function. Two new aminocoumarins, cacibiocin A and B, were identified in the culture broth of C. acidiphila. Heterologous expression of the putative gene cluster in Streptomyces coelicolor M1152 confirmed that this cluster is responsible for cacibiocin biosynthesis. Furthermore, total production levels of cacibiocins could be increased by heterologous expression and screening of different culture media from an initial yield of 4.9 mg L(-1) in C. acidiphila to 60 mg L(-1) in S. coelicolor M1152. By HR-MS and NMR analysis, cacibiocin A was found to contain a 3-amino-4,7-dihydroxycoumarin moiety linked by an amide bond to a pyrrole-2,5-dicarboxylic acid. The latter structural motif has not been identified previously in any natural compound. Additionally, cacibiocin B contains two chlorine atoms at positions 6' and 8' of the aminocoumarin moiety.
authors.affiliation: Eberhard-Karls-Universität Tübingen, Pharmazeutische Biologie, Auf der Morgenstelle 8, 72076 Tübingen (Germany); German Centre for Infection Research (DZIF), Partner site Tübingen (Germany).
authors.forename: Judith
authors.initials: J
authors.lastname: Zettler
authors.forename: Haiyang
authors.initials: H
authors.lastname: Xia
authors.forename: Nadja
authors.initials: N
authors.lastname: Burkard
authors.forename: Andreas
authors.initials: A
authors.lastname: Kulik
authors.forename: Stephanie
authors.initials: S
authors.lastname: Grond
authors.forename: Lutz
authors.initials: L
authors.lastname: Heide
authors.forename: Alexander K
authors.initials: AK
authors.lastname: Apel
mesh_terms: D000192:Actinomycetales / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D049933:Aminocoumarins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000737:chemistry* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D016680:Genome, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008968:Molecular Conformation; D005810:Multigene Family; D011758:Pyrroles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D013302:Streptomyces / Q000378:metabolism
chemical_list: D049933:Aminocoumarins; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001688:Biological Products; D011758:Pyrroles; D011994:Recombinant Proteins
keywords: actinobacteria; gene expression; heterologous expression; natural products; structure elucidation