Kutznerides 1−4, Depsipeptides from the Actinomycete Kutzneria sp. 744 Inhabiting Mycorrhizal Roots of Picea abies Seedlings

Broberg, Anders; Menkis, Audrius; Vasiliauskas, Rimvydas

doi:10.1021/np050378g

Cited by 79 publications

(93 citation statements)

References 24 publications

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“…744. The producing organism that yields kutznerides 1-9 was cultivated as described (1) and its genomic DNA isolated. Amplicons obtained by PCR using genomic DNA as a template and degenerate primers for both flavin and mononuclear nonheme iron halogenases [supporting information (SI) Table 2] were sequenced, identifying two distinct flavin-dependent halogenases and one Fe(II)-dependent halogenase.…”

Section: Resultsmentioning

confidence: 99%

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Cloning and characterization of the biosynthetic gene cluster for kutznerides

Fujimori

Hrvatin²,

Neumann³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

155

202

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Kutznerides, actinomycete-derived cyclic depsipetides, consist of six nonproteinogenic residues, including a highly oxygenated tricyclic hexahydropyrroloindole, a chlorinated piperazic acid, 2-(1-methylcyclopropyl)-glycine, a ␤-branched-hydroxy acid, and 3-hydroxy glutamic acid, for which biosynthetic logic has not been elucidated. Herein we describe the biosynthetic gene cluster for the kutzneride family, identified by degenerate primer PCR for halogenating enzymes postulated to be involved in biosyntheses of these unusual monomers. The 56-kb gene cluster encodes a series of six nonribosomal peptide synthetase (NRPS) modules distributed over three proteins and a variety of tailoring enzymes, including both mononuclear nonheme iron and two flavindependent halogenases, and an array of oxygen transfer catalysts. The sequence and organization of NRPS genes support incorporation of the unusual monomer units into the densely functionalized scaffold of kutznerides. Our work provides insight into the formation of this intriguing class of compounds and provides a foundation for elucidating the timing and mechanisms of their biosynthesis.chlorination ͉ halogenases ͉ nonribosomal peptide biosynthesis K utznerides are antifungal and antimicrobial cyclic hexadepsipeptides isolated from the soil actinomycete Kutzneria sp. 744 (1). Structural elucidation of these metabolites revealed nine related compounds composed of five unusual nonproteinogenic amino acids and one hydroxy acid ( Fig. 1) but differing in the extent of substitution and stereochemistry of constituent residues (2). All kutznerides contain 2-(1-methylcyclopropyl)-D-glycine (MecPGly) connected to the ␣-hydroxyl moiety of either (S)-2-hydroxy-3-methylbutyric or (S)-2-hydroxy-3,3-dimethylbutyric acid. The hydroxy acid residue is followed by a piperazic acid moiety, found in four distinct forms: as piperazic acid in kutznerides 1, 3, 5, and 7; as dehydropiperazate in kutznerides 4 and 9; as ␥-chloro-piperazate in kutznerides 2 and 8; and as ␥-hydroxy-dehydropiperazate in kutzneride 6. Furthermore, kutznerides contain O-methyl-L-serine and either the threo or erythro isomer of 3-hydroxy-D-glutamate. Finally, an unusual tricyclic dihalogenated (2S,3aR,8aS)-6,7-dichloro-3a-hydroxy-hexahydropyrrolo[2,3-b]indole-2-carboxylic acid (PIC) is conserved in all structurally characterized kutznerides. The structural subunits of kutznerides suggest unusual enzymatic mechanisms involved in their biosynthesis.Recently, our laboratory has elucidated the enzymatic logic of carbon-chlorine bond formation during the biosynthesis of several chlorinated secondary metabolites. Among these, dichlorination of the pyrrole moiety in the biosynthesis of pyoluteorin (3) and chlorination of tryptophan in rebeccamycin biosynthesis (4) are carried out by the flavin-dependent halogenases PltA and RebH, respectively. The work of van Pee and coworkers (5) on the pyrrolnitrin halogenase PrnA demonstrated the necessity of FADH 2 , chloride, and oxygen for catalytic activity of flavoprotein halogenase...

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Section: Resultsmentioning

confidence: 99%

“…744 (1). Structural elucidation of these metabolites revealed nine related compounds composed of five unusual nonproteinogenic amino acids and one hydroxy acid ( Fig.…”

mentioning

confidence: 99%

Cloning and characterization of the biosynthetic gene cluster for kutznerides

Fujimori

Hrvatin²,

Neumann³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

155

202

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“…Substances produced by endophytes may be toxic to plant pathogens or act as repellents against insects or herbivores [20]. Some endophytes of woody roots may be selectively antagonistic to plant pathogens and/or pest insects and may be an important source of new biologically active secondary metabolites [21].…”

Section: Introductionmentioning

confidence: 99%

High-Throughput Sequencing Shows High Fungal Diversity and Community Segregation in the Rhizospheres of Container-Grown Conifer Seedlings

Menkis

Burokienė

Stenlid

et al. 2016

Forests

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Forest nurseries in Sweden produce ca. 360 million seedlings of Pinus sylvestris L. and Picea abies (L.) Karst. annually. Fungi represent the largest microbial component in rhizospheres and may significantly affect health and, consequently, quality of the seedlings. The aim of this study was to assess fungi focusing on pathogens in roots and the sphagnum peat growth substrate of healthy-looking P. sylvestris and P. abies seedlings from nine forest nurseries situated in northern, central and southern regions of Sweden. We hypothesized that nursery stock and the growth substrate can provide a venue for dissemination of fungal diseases. In each nursery and for each tree species, 100 seedlings with the growth substrate were collected during the dormant period. DNA was isolated from parts of root systems and from samples of the growth substrate, amplified using internal transcribed spacer of rDNA as a marker and 454-sequenced. Clustering at 98.5% similarity of 169,844 high-quality sequences resulted in 619 non-singleton fungal taxa. Although results showed that management practices in forest nurseries generally give a healthy stock, latent establishment of pathogenic fungi in both roots and the growth substrate supported the hypothesis. Furthermore, seedling roots and the growth substrate were inhabited by distinct communities of fungi, and lifestyles of these fungi largely determined community segregation into particular ecological niche.

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“…Diese kann durch das intramolekulare Amid abgefangen werden, wodurch ein Pyrroloindol wie in der Kutznerid-Biosynthese aufgebaut wird (Abbildung 6). [147] Diese Modifikationen laufen entweder während der Verlängerung der linearen Kette oder nach Bildung des makrocyclischen Peptidgerüsts ab. Am freien Trp sind sie nicht mçglich.…”

Section: Bildung Des Pyrroloindol-tricyclusunclassified

Nichtproteinogene Aminosäurebausteine für Peptidgerüste aus nichtribosomalen Peptiden und hybriden Polyketiden

2013

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Frei vorkommende nichtproteinogene Aminosäuren sind schon lange wegen ihrer antimetabolen Eigenschaften bekannt. Entdeckt werden sie meist aufgrund der Reaktivität gegenüber der katalytischen Wirkung der Zielenzyme. Führt man sie regiospezifisch in biogene Peptide und Proteine ein, kann es möglich werden, eine neue Ära der Medizinalchemie an der Grenze zwischen kleinen und großen Wirkstoffen einzuleiten. Außerdem eröffnet die ortsspezifische Funktionalisierung von Proteinen besonders attraktive Strategien für die posttranslationale Proteinmodifizierung. Auch bieten viele der Aminosäuren, die von der Natur nicht für den Einbau in Proteine ausgewählt wurden, reiche architektonische Möglichkeiten bei Einführung in ribosomal hergestellte Polypeptide. Dieser Aufsatz fasst die Biosynthesewege zu den wichtigsten Klassen nichtkanonischer Bausteine und deren Stoffwechsellogik zusammen, die in nichtribosomalen Peptidgerüsten und nichtribosomalen Peptid‐Polyketid‐Hybriden resultieren.

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Kutznerides 1−4, Depsipeptides from the Actinomycete Kutzneria sp. 744 Inhabiting Mycorrhizal Roots of Picea abies Seedlings

Cited by 79 publications

References 24 publications

Cloning and characterization of the biosynthetic gene cluster for kutznerides

Cloning and characterization of the biosynthetic gene cluster for kutznerides

High-Throughput Sequencing Shows High Fungal Diversity and Community Segregation in the Rhizospheres of Container-Grown Conifer Seedlings

Nichtproteinogene Aminosäurebausteine für Peptidgerüste aus nichtribosomalen Peptiden und hybriden Polyketiden

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