title: Chaxamycins A-D, bioactive ansamycins from a hyper-arid desert Streptomyces sp.
abstract: Streptomyces sp. strain C34, isolated from soil collected in the Chilean hyper-arid Atacama Desert, was cultured on different media, resulting in the isolation and identification of four new ansamycin-type polyketides. The organism was selected for chemical investigation on the basis of a genome-mining PCR-based experiment targeting the gene encoding rifamycin-specific 3-amino-5-hydroxybenzoic acid synthetase (AHBA). The isolated compounds were structurally characterized using NMR and MS techniques and named chaxamycins A-D (1-4). Compounds 1-4 were tested for their antibacterial activity against Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 and for their ability to inhibit the intrinsic ATPase activity of the heat shock protein 90 (Hsp90). Chaxamycin D (4), which showed a selective antibacterial activity against S. aureus ATCC 25923, was tested further against a panel of MRSA clinical isolates. In a virtual screening experiment, chaxamycins A-D (1-4) have also been docked into the ATP-binding pocket in the N-terminal domain of the Hsp90, and the observed interactions are discussed.
authors.affiliation: Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen , Meston Walk, Aberdeen AB24 3UE, Scotland, UK.
authors.forename: Mostafa E
authors.initials: ME
authors.lastname: Rateb
authors.forename: Wael E
authors.initials: WE
authors.lastname: Houssen
authors.forename: Markus
authors.initials: M
authors.lastname: Arnold
authors.forename: Mostafa H
authors.initials: MH
authors.lastname: Abdelrahman
authors.forename: Hai
authors.initials: H
authors.lastname: Deng
authors.forename: William T A
authors.initials: WT
authors.lastname: Harrison
authors.forename: Chinyere K
authors.initials: CK
authors.lastname: Okoro
authors.forename: Juan A
authors.initials: JA
authors.lastname: Asenjo
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Andrews
authors.forename: Gail
authors.initials: G
authors.lastname: Ferguson
authors.forename: Alan T
authors.initials: AT
authors.lastname: Bull
authors.forename: Michael
authors.initials: M
authors.lastname: Goodfellow
authors.forename: Rainer
authors.initials: R
authors.lastname: Ebel
authors.forename: Marcel
authors.initials: M
authors.lastname: Jaspars
mesh_terms: D000251:Adenosine Triphosphatases / Q000187:drug effects; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006836:Hydro-Lyases / Q000235:genetics / Q000378:metabolism; D047029:Lactams, Macrocyclic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D015394:Molecular Structure; D013302:Streptomyces / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D000251:Adenosine Triphosphatases; C111160:3-amino-5-hydroxybenzoic acid synthase; D006836:Hydro-Lyases