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Regulation and biosynthesis of syringolin and syringolin-like molecules and investigation of their role and mode of action in the interaction of bacteria with plants and other eukaryotes

English title Regulation and biosynthesis of syringolin and syringolin-like molecules and investigation of their role and mode of action in the interaction of bacteria with plants and other eukaryotes
Applicant Dudler Robert
Number 115970
Funding scheme Project funding
Research institution Institut für Pflanzen- und Mikrobiologie Universität Zürich
Institution of higher education University of Zurich - ZH
Main discipline Botany
Start/End 01.10.2007 - 31.12.2011
Approved amount 369'900.00
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All Disciplines (2)

Discipline
Botany
Experimental Microbiology

Keywords (6)

hypersensitive reaction; powdery mildew; syringolin; glidobactin; Burkholderia pseudomallei; Pseudomonas sringae

Lay Summary (English)

Lead
Lay summary
We have previously identified syringolin A, an unusual peptide derivative that is synthesized by a mixed non-ribosomal peptide synthetase/polyketide synthetase and that is secreted by the phytopathogenic bacterium Pseudomonas syringae pv. syringae. Spray application of syringolin A has the remarkable property to trigger hypersensitive cell death at infection sites of powdery mildew-infected wheat and Arabidopsis plants. Changes in global gene activity were monitored in wheat and Arabidopsis after spraying of uninfected and powdery mildew-infected plants with syringolin A or a control solution. The results were to a large degree congruent in both species and allowed to formulate a hypothesis about the cellular target and the mode of action of syringolin A that will be tested in this project.Syringolin A is a tripeptide derivative that is synthesized by a mixed non-ribosomal peptide synthetase/polyketide synthetase that is encoded by a gene cluster we previously cloned. The architecture of this gene cluster allowed us to derive a unique model explaining the biosynthesis of syringolin A. Structurally, syringolin is similar in its tripeptide part to the glidobactins, which are acylated tripeptide derivatives. Glidobactins are reported to have antifungal and antitumor activity. The biosynthesis model of the peptide part of syringolin A nicely can accommodate also the tripeptide part of glidobactins. Searching the nearly 600 available eubacterial genome sequences for genes with an architecture similar to the one of the syringolin synthetase genes resulted in the identification of three taxa that are hypothesized to encode synthetases of twelve-membered ring-containing tripeptides: Burkholderia pseudomallei, a dangerous human pathogen and causal agent of melioidosis, Photorhabdus luminescens, an insect pathogen, and Burkholderia mallei, an animal pathogen and causal agent of glanders.A PCR fragment was successfully amplified from genomic DNA of DSM 7029, a bacterium of uncertain origin reported in the literature to synthesize glidobactins. We have cloned that genes encoding the glidobactin synthetase from a bacterium producing the compound. We will also conduct experiments to elucidate the mode of action of glidobatin.The experiments proposed in this project will identify the target on syringolin A and thus identify a new way of how a plant pathogen may manipulate the physiology of the host. Syringolin A belongs to the unique class of compounds containing a twelve-membered ring structure which have an intriguing distribution in nature as far as it is currently known. Elucidation of the biology and mode of action of this class not only increases knowledge about how a plant pathogen interacts with plants, but may also have implications for other pathogens such as Burkholderia pseudomallei, the causing agent of melioidosis.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Pseudomonas syringae Virulence Factor Syringolin A Counteracts Stomatal Immunity by Proteasome Inhibition
Schellenberg B, Ramel C, Dudler R (2010), Pseudomonas syringae Virulence Factor Syringolin A Counteracts Stomatal Immunity by Proteasome Inhibition, in MOLECULAR PLANT-MICROBE INTERACTIONS, 23(10), 1287-1293.
Convergent Synthesis and Biological Evaluation of Syringolin A and Derivatives as Eukaryotic 20S Proteasome Inhibitors
Clerc J, Schellenberg B, Groll M, Bachmann AS, Huber R, Dudler R, Kaiser M (2010), Convergent Synthesis and Biological Evaluation of Syringolin A and Derivatives as Eukaryotic 20S Proteasome Inhibitors, in EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, (21), 3991-4003.
Syrbactin class proteasome inhibitor-induced apoptosis and autophagy occurs in association with p53 accumulation and Akt/PKB activation in neuroblastoma
Archer CR, Koomoa DLT, Mitsunaga EM, Clerc J, Shimizu M, Kaiser M, Schellenberg B, Dudler R, Bachmann AS (2010), Syrbactin class proteasome inhibitor-induced apoptosis and autophagy occurs in association with p53 accumulation and Akt/PKB activation in neuroblastoma, in BIOCHEMICAL PHARMACOLOGY, 80(2), 170-178.
Syringolin A Selectively Labels the 20 S Proteasome in Murine EL4 and Wild-Type and Bortezomib-Adapted Leukaemic Cell Lines
Clerc J, Florea BI, Kraus M, Groll M, Huber R, Bachmann AS, Dudler R, Driessen C, Overkleeft HS, Kaiser M (2009), Syringolin A Selectively Labels the 20 S Proteasome in Murine EL4 and Wild-Type and Bortezomib-Adapted Leukaemic Cell Lines, in CHEMBIOCHEM, 10(16), 2638-2643.
Biosynthesis of the proteasome inhibitor syringolin A: the ureido group joining two amino acids originates from bicarbonate
Ramel C, Tobler M, Meyer M, Bigler L, Ebert MO, Schellenberg B, Dudler R (2009), Biosynthesis of the proteasome inhibitor syringolin A: the ureido group joining two amino acids originates from bicarbonate, in BMC BIOCHEMISTRY, 10(26), 1-9.
Synthetic and structural studies on syringolin A and B reveal critical determinants of selectivity and potency of proteasome inhibition
Clerc J, Groll M, Illich DJ, Bachmann AS, Huber R, Schellenberg B, Dudler R, Kaiser M (2009), Synthetic and structural studies on syringolin A and B reveal critical determinants of selectivity and potency of proteasome inhibition, in PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 106(16), 6507-6512.
A plant pathogen virulence factor inhibits the eukaryotic proteasome by a novel mechanism
Groll M, Schellenberg B, Bachmann AS, Archer CR, Huber R, Powell TK, Lindow S, Kaiser M, Dudler R (2008), A plant pathogen virulence factor inhibits the eukaryotic proteasome by a novel mechanism, in NATURE, 452(7188), 755-755.
Syringolin A: Action on Plants, Regulation of Biosynthesis, and Phylogenetic Occurrence of Structurally Related Compounds.
Schellenberg Barbara, Ramel Christina, Dudler Robert (2008), Syringolin A: Action on Plants, Regulation of Biosynthesis, and Phylogenetic Occurrence of Structurally Related Compounds., in Collmer, Mansfield, Ullrich, Murillo, Schaad, Iacobellis, Fatmi (ed.), 249-258.

Awards

Title Year
Auszeichnung der Dissertation 2008

Associated projects

Number Title Start Funding scheme
100046 Analysis of the Syringolin-Triggered Tranformation of Compatibility to Incompatibilty in Powdery Mildew-Infected Plants 01.07.2003 Project funding
134936 Structure, function and biosynthesis of syrbactins 01.01.2012 Project funding

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