Collinone, a New Recombinant Angular Polyketide Antibiotic Made by an Engineered Streptomyces Strain.

Martín, Robert R.; Sierner, Olov; Álvarez, Miguel A.; Clercq, Erik De; Bailey, James E.; Minas, Wolfgang

doi:10.7164/antibiotics.54.239

Cited by 43 publications

(48 citation statements)

References 34 publications

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“…strain PGA 22 to S. collinus contains sequences that are responsible for the biosynthesis of rubromycins or similar compounds, because in this group Streptomyces sp. strain PGA 64 and S. collinus, from which the genes responsible for rubromycin biosynthesis have recently been cloned (17), are known to produce rubromycins. A variety of sequences also cluster around the aureolic acid producer S. argillaceus, but it is not possible to propose boundaries for this group because there is no information about the compounds produced by the surrounding strains.…”

Section: Resultsmentioning

confidence: 99%

Molecular Evolution of Aromatic Polyketides and Comparative Sequence Analysis of Polyketide Ketosynthase and 16S Ribosomal DNA Genes from Various Streptomyces Species

Metsä‐Ketelä

Halo

Munukka

et al. 2002

Appl Environ Microbiol

117

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A 613-bp fragment of an essential ketosynthase gene from the biosynthetic pathway of aromatic polyketide antibiotics was sequenced from 99 actinomycetes isolated from soil. Phylogenetic analysis showed that the isolates clustered into clades that correspond to the various classes of aromatic polyketides. Additionally, sequencing of a 120-bp fragment from the ␥-variable region of 16S ribosomal DNA (rDNA) and subsequent comparative sequence analysis revealed incongruity between the ketosynthase and 16S rDNA phylogenetic trees, which strongly suggests that there has been horizontal transfer of aromatic polyketide biosynthesis genes. The results show that the ketosynthase tree could be used for DNA fingerprinting of secondary metabolites and for screening interesting aromatic polyketide biosynthesis genes. Furthermore, the movement of the ketosynthase genes suggests that traditional marker molecules like 16S rDNA give misleading information about the biosynthesis potential of aromatic polyketides, and thus only molecules that are directly involved in the biosynthesis of secondary metabolites can be used to gain information about the biodiversity of antibiotic production in different actinomycetes.Soil actinomycetes, especially those that belong to the genus Streptomyces, have been the focus of intensive research for the past several decades. The interest in Streptomyces arose from the finding that this group of bacteria seems to have the ability to produce a large variety of different bioactive compounds that have a wide spectrum of activity. From the 1950s to the mid-1970s numerous new bioactive molecules were discovered through large screening programs, and these molecules subsequently found their way into various clinical uses ranging from control of infections to cancer treatment (21).In more recent years, modern high-throughput screening methods have exponentially increased the number of strains screened annually, but the number of novel compounds discovered has not increased in the same proportion. One of the many reasons, presumably the most important one, for this problem is that old molecules (and strains) are being rediscovered with the screening procedures that are in use today (21).In a previous paper (18) Metsä-Ketelä et al. reported a method that could be used for preliminary classification of strains on the basis of their genetic abilities to produce various compounds belonging to the aromatic polyketide group. This method is based on PCR amplification of a gene fragment that is essential in the biosynthesis pathway of aromatic polyketides and on analysis of the amplified regions by phylogenetic methods. The degenerate primers designed for this purpose amplify a portion of a ketosynthase gene (KS ␣ ), which in collaboration with KS ␤ and an acyl carrier protein condenses small carboxylic acids in a stepwise manner to form a long polyketide chain that is subsequently folded into a range of different aromatic compounds by various ketoreductases, cyclases, and aromatases. Later, the molecule formed is of...

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Section: Resultsmentioning

confidence: 99%

Molecular Evolution of Aromatic Polyketides and Comparative Sequence Analysis of Polyketide Ketosynthase and 16S Ribosomal DNA Genes from Various Streptomyces Species

Metsä‐Ketelä

Halo

Munukka

et al. 2002

Appl Environ Microbiol

117

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“…In an early example, Martin et al identified a cryptic PKS gene cluster in the genome of Streptomyces collinus by heterologous expression of the cluster in the first engineered host, S. coelicolor CH999 (266). More well-developed surrogate hosts have been derived in S. coelicolor and the industrial strain S. avermitilis.…”

Section: Heterologous Expression In Engineered Hostsmentioning

confidence: 99%

Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

Liu

Chater

Chandra

et al. 2013

Microbiol Mol Biol Rev

610

536

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SUMMARY Streptomycetes are the most abundant source of antibiotics. Typically, each species produces several antibiotics, with the profile being species specific. Streptomyces coelicolor , the model species, produces at least five different antibiotics. We review the regulation of antibiotic biosynthesis in S. coelicolor and other, nonmodel streptomycetes in the light of recent studies. The biosynthesis of each antibiotic is specified by a large gene cluster, usually including regulatory genes (cluster-situated regulators [CSRs]). These are the main point of connection with a plethora of generally conserved regulatory systems that monitor the organism's physiology, developmental state, population density, and environment to determine the onset and level of production of each antibiotic. Some CSRs may also be sensitive to the levels of different kinds of ligands, including products of the pathway itself, products of other antibiotic pathways in the same organism, and specialized regulatory small molecules such as gamma-butyrolactones. These interactions can result in self-reinforcing feed-forward circuitry and complex cross talk between pathways. The physiological signals and regulatory mechanisms may be of practical importance for the activation of the many cryptic secondary metabolic gene cluster pathways revealed by recent sequencing of numerous Streptomyces genomes.

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“…[116] codiert. Auf der Basis von putativen Genfunktionen und einem Shunt-Produkt oder Intermediat, Collinon (47), das über die Expression des unvollständigen Rubromycin-Biosynthese-Genclusters [117] erhalten wurde, sowie der Bildung von Lenticulon (48) in einer gezielten Oxygenase-Mutante, wurde ein Biosynthesemodell vorgeschlagen. [118] Diesem Modell zufolge werden auf dem Weg zum Spiro-Endprodukt nacheinander vier Kohlenstoff-Kohlenstoff-Bindungen gespalten.…”

Section: Aberrante Cyclisierung Aromatischer Polyketide (Favorskiiase)unclassified

Die biosynthetische Grundlage der Polyketid‐Vielfalt

Hertweck

2009

Angewandte Chemie

205

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Molekulares Lego: Polyketide bilden eine äußerst vielfältige Gruppe von Naturstoffen mit faszinierenden Kohlenstoffgerüsten (siehe Beispiele), die aus einfachen Acyl‐Bausteinen synthetisiert werden. Das Zusammenspiel von Chemie, Biochemie und Genetik lieferte wichtige Einblicke in die Programmierung des Polyketid‐Aufbaus und die beteiligten, komplexen Enzymsysteme. Dieser Aufsatz behandelt aktuelle Entwicklungen auf diesem Forschungsgebiet.magnified imagePolyketide bilden eine der größten Naturstoffklassen. Viele dieser Verbindungen – oder Derivate davon – sind wichtige Therapeutika, aber viele sind auch berüchtigte, Lebensmittel verderbende Toxine oder Virulenzfaktoren. Besonders bemerkenswert ist, dass sich die Verbindungen dieser heterogenen Gruppe, zu denen Polyether, Polyene, Polyphenole, Makrolide und Endiine gehören, hauptsächlich von einem der einfachsten natürlichen Bausteine ableiten: Essigsäure. Chemische, genetische und biochemische Untersuchungen haben Aufschluss über die Biosyntheseprogramme gegeben, die zur enormen Strukturvielfalt von Polyketiden führen. Dieser Aufsatz behandelt kürzlich aufgeklärte Biosynthesemechanismen, nach denen höchst unterschiedliche und komplexe Moleküle synthetisiert werden.

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Collinone, a New Recombinant Angular Polyketide Antibiotic Made by an Engineered Streptomyces Strain.

Cited by 43 publications

References 34 publications

Molecular Evolution of Aromatic Polyketides and Comparative Sequence Analysis of Polyketide Ketosynthase and 16S Ribosomal DNA Genes from Various Streptomyces Species

Molecular Evolution of Aromatic Polyketides and Comparative Sequence Analysis of Polyketide Ketosynthase and 16S Ribosomal DNA Genes from Various Streptomyces Species

Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

Die biosynthetische Grundlage der Polyketid‐Vielfalt

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