Biosynthesis and structure of aeruginoside 126A and 126B, cyanobacterial peptide glycosides bearing a 2-carboxy-6-hydroxyoctahydroindole moiety.
Aeruginosins represent a group of peptide metabolites isolated from various cyanobacterial genera and from marine sponges that potently inhibit different types of serine proteases. Members of this family are characterized by the presence of a 2-carboxy-6-hydroxyoctahydroindole (Choi) moiety. We have identified and fully sequenced a NRPS gene cluster in the genome of the cyanobacterium Planktothrix agardhii CYA126/8. Insertional mutagenesis of a NRPS component led to the discovery and structural elucidation of two glycopeptides that were designated aeruginoside 126A and aeruginoside 126B. One variant of the aglycone contains a 1-amino-2-(N-amidino-Delta(3)-pyrrolinyl)ethyl moiety at the C terminus, the other bears an agmatine residue. In silico analyses of the aeruginoside biosynthetic genes aerA-aerI as well as additional mutagenesis and feeding studies allowed the prediction of enzymatic steps leading to the formation of aeruginosides and the unusual Choi moiety.
Ishida
Keishi
K
Humboldt University Berlin, Institute of Biology, 10115 Berlin, Germany.|Leibniz-Institute for Natural Product Research and Infection Biology (HKI) Dept. of Biomolecular Chemistry , 07745 Jena, Germany.
Christiansen
Guntram
G
Humboldt University Berlin, Institute of Biology, 10115 Berlin, Germany.|University of Hawaii at Manoa, Department of Chemistry, Honolulu, Hawaii 96822, USA.
Yoshida
Wesley Y
WY
University of Hawaii at Manoa, Department of Chemistry, Honolulu, Hawaii 96822, USA.
Kurmayer
Rainer
R
Austrian Academy of Science, Institute for Limnology, 5310 Mondsee, Austria.
Welker
Martin
M
Technical University Berlin, Institute of Chemistry, 10587 Berlin, Germany.
Valls
Nativitat
N
University of Barcelona, Faculty of Pharmacy, 08028-Barcelona, Spain.
Bonjoch
Josep
J
University of Barcelona, Faculty of Pharmacy, 08028-Barcelona, Spain.
Hertweck
Christian
C
Leibniz-Institute for Natural Product Research and Infection Biology (HKI) Dept. of Biomolecular Chemistry , 07745 Jena, Germany.
Börner
Thomas
T
Humboldt University Berlin, Institute of Biology, 10115 Berlin, Germany.
Hemscheidt
Thomas
T
University of Hawaii at Manoa, Department of Chemistry, Honolulu, Hawaii 96822, USA.|Cancer Research Center of Hawaii, Honolulu, Hawaii 96813, USA.
Dittmann
Elke
E
Humboldt University Berlin, Institute of Biology, 10115 Berlin, Germany.
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D003198:Computer Simulation; D000458:Cyanobacteria / Q000737:chemistry* / Q000235:genetics; D004252:DNA Mutational Analysis; D004269:DNA, Bacterial / Q000235:genetics; D006020:Glycopeptides; D006027:Glycosides / Q000096:biosynthesis* / Q000138:chemical synthesis*; D007211:Indoles / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D005810:Multigene Family / Q000235:genetics; D016296:Mutagenesis; D019151:Peptide Library; D010957:Plasmids / Q000235:genetics; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization
C436762:6-hydroxyoctahydroindole-2-carboxylic acid; D004269:DNA, Bacterial; D006020:Glycopeptides; D006027:Glycosides; D007211:Indoles; D019151:Peptide Library; D015842:Serine Proteinase Inhibitors; C521764:aeruginoside 126A; C521766:aeruginoside 126B