Pyxipyrrolones: Structure Elucidation and Biosynthesis of Cytotoxic Myxobacterial Metabolites

Louise Kjaerulff; Ritesh Raju; Fabian Panter; Ullrich Scheid; Ronald Garcia; Jennifer Herrmann; Rolf Müller

doi:10.1002/anie.201704790

Pyxipyrrolones: Structure Elucidation and Biosynthesis of Cytotoxic Myxobacterial Metabolites

Louise Kjaerulff, Ritesh Raju, Fabian Panter, Ullrich Scheid, Ronald Garcia, Jennifer Herrmann, Rolf Müller^*

^*Corresponding author af dette arbejde

8 Citationer (Scopus)

Abstract

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 (μm range) with pyxipyrrolone B having 2- to 11-fold higher activity than A, although they differ only by one methylene group.

Originalsprog	Engelsk
Tidsskrift	Angewandte Chemie - International Edition
Vol/bind	56
Udgave nummer	32
Sider (fra-til)	9614-9618
Antal sider	5
ISSN	1433-7851
DOI	https://doi.org/10.1002/anie.201704790
Status	Udgivet - 1 aug. 2017
Udgivet eksternt	Ja

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10.1002/anie.201704790

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title = "Pyxipyrrolones: Structure Elucidation and Biosynthesis of Cytotoxic Myxobacterial Metabolites",

abstract = "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 (μm range) with pyxipyrrolone B having 2- to 11-fold higher activity than A, although they differ only by one methylene group.",

keywords = "biosynthesis, cytotoxicity, myxobacteria, secondary metabolites, structure elucidation",

author = "Louise Kjaerulff and Ritesh Raju and Fabian Panter and Ullrich Scheid and Ronald Garcia and Jennifer Herrmann and Rolf M{\"u}ller",

year = "2017",

month = aug,

day = "1",

doi = "10.1002/anie.201704790",

language = "English",

volume = "56",

pages = "9614--9618",

journal = "Angewandte Chemie International Edition",

issn = "1433-7851",

publisher = "Wiley-VCH Verlag GmbH & Co. KGaA",

number = "32",

}

TY - JOUR

T1 - Pyxipyrrolones

T2 - Structure Elucidation and Biosynthesis of Cytotoxic Myxobacterial Metabolites

AU - Kjaerulff, Louise

AU - Raju, Ritesh

AU - Panter, Fabian

AU - Scheid, Ullrich

AU - Garcia, Ronald

AU - Herrmann, Jennifer

AU - Müller, Rolf

PY - 2017/8/1

Y1 - 2017/8/1

N2 - 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 (μm range) with pyxipyrrolone B having 2- to 11-fold higher activity than A, although they differ only by one methylene group.

AB - 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 (μm range) with pyxipyrrolone B having 2- to 11-fold higher activity than A, although they differ only by one methylene group.

KW - biosynthesis

KW - cytotoxicity

KW - myxobacteria

KW - secondary metabolites

KW - structure elucidation

U2 - 10.1002/anie.201704790

DO - 10.1002/anie.201704790

M3 - Journal article

C2 - 28590072

AN - SCOPUS:85021809968

SN - 1433-7851

VL - 56

SP - 9614

EP - 9618

JO - Angewandte Chemie International Edition

JF - Angewandte Chemie International Edition

IS - 32

ER -

Pyxipyrrolones: Structure Elucidation and Biosynthesis of Cytotoxic Myxobacterial Metabolites

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