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Pyxipyrrolones: Structure Elucidation and Biosynthesis of Cytotoxic Myxobacterial Metabolites
Author(s) -
Kjaerulff Louise,
Raju Ritesh,
Panter Fabian,
Scheid Ullrich,
Garcia Ronald,
Herrmann Jennifer,
Müller Rolf
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201704790
Subject(s) - myxobacteria , stereochemistry , biosynthesis , chemistry , gene cluster , methylene , gene , biochemistry , biology , bacteria , genetics , organic chemistry
In the search for new secondary metabolites from myxobacteria, a strain from the genus Pyxidicoccus was investigated. This led to the identification of a new class of natural products showing structural novelty and interesting biological activity. Isolation and structure elucidation of two analogues led to the identification of pyxipyrrolone A and B, harboring the novel 3‐methylene‐2,3,4,5,6,7,8,9‐octahydro‐1H‐benzo[e]isoindol‐1‐one scaffold. Mosher's ester analysis combined with NMR studies allowed the determination of all stereocenters but one. Genome sequencing of the producer strain led to the identification of a putative biosynthetic gene cluster for the pyxipyrrolones. The compounds showed activity against several cancer cell lines (μ m range) with pyxipyrrolone B having 2‐ to 11‐fold higher activity than A, although they differ only by one methylene group.