13-Deoxytetrodecamycin, a new tetronate ring-containing antibiotic that is active against multidrug-resistant Staphylococcus aureus

Gverzdys, Tomas; Hart, Michael Kamin; Pimentel‐Elardo, Sheila Marie; Tranmer, Geoffrey K.; Nodwell, Justin R.

doi:10.1038/ja.2015.60

Cited by 7 publications

(7 citation statements)

References 31 publications

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“…WAC04657, 13-dTDM appears to be the end-product of this biosynthetic pathway, 34 yet it is a logical next step to add a hydroxyl to C-13 to generate TDM. Next, reduction of the exo-methylene to a methyl would generate dhTDM.…”

Section: Biosynthesismentioning

confidence: 99%

“…The change in the decalin ring results in marginally greater activity against Gram-positive organisms (from 1 to 8 lg mL À1 , 3.14 to 25.2 lM) when compared to TDM. 34 Given the anti-MRSA activity, the presence of a Michael acceptor, and the lack of knowledge about the TDM-group molecules, we went on to identify the biosynthetic gene cluster (the ted genes) that encodes 13-dTDM. 50 We identified the same cluster in three other strains of Streptomyces.…”

Section: Introductionmentioning

confidence: 99%

“…,34 2. History of the tetrodecamycins TDM was first reported in 1994 in a brief letter followed later by a description of the producing strain, fermentation, isolation, and the structural elucidation of TDM and a related compound, dhTDM…”

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confidence: 99%

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Tetrodecamycin: An unusual and interesting tetronate antibiotic

Gverzdys

Kramer

Nodwell

2016

Bioorganic & Medicinal Chemistry

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The tetrodecamycins are a group of secondary metabolites that are characterized by the presence of a tetronate ring in their structure. Originally discovered for their antibiotic activity against Photobacterium damselae ssp. piscicida, the causative agent of pseudotuberculosis in fish, this family of molecules has also been shown to have potent antibiotic activity against methicillin-resistant Staphylococcus aureus. Due to their small size and highly cyclized nature, they represent an unusual member of the much larger group of bioactive molecules called the tetronates. Herein, we review what is known about the mechanism of action of these molecules and also present a hypothesis for their biosynthesis. A deeper understanding of the tetrodecamycins will provide a more holistic view of the tetronate-family, provide new chemical probes of bacterial biology, and may provide therapeutic lead molecules.

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Section: Biosynthesismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tetrodecamycin: An unusual and interesting tetronate antibiotic

Gverzdys

Kramer

Nodwell

2016

Bioorganic & Medicinal Chemistry

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“…For 454 sequencing (data not shown), genomic DNA was extracted as previously described (7). The genome was sequenced on a 454 GS FLXϩ instrument at McMaster University using 37.5% of a sequencing plate.…”

Section: Methodsmentioning

confidence: 99%

“…Intergenic conjugations were performed from E. coli ET12567/pUZ8002 host strains to Streptomyces on mannitol-soya flour (MS) agar as previously described (15) Plasmid construction and genetic manipulation of Streptomyces. Chromosomal DNA was isolated from WAC04657 as previously described (7). To build the plasmid for disrupting the tedF1 gene (pOJ260-tedF1 frag.…”

Section: Methodsmentioning

confidence: 99%

Biosynthetic Genes for the Tetrodecamycin Antibiotics

Gverzdys

Nodwell

2016

J Bacteriol

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We recently described 13-deoxytetrodecamycin, a new member of the tetrodecamycin family of antibiotics. A defining feature of these molecules is the presence of a five-membered lactone called a tetronate ring. By sequencing the genome of a producer strain, Streptomyces sp. strain WAC04657, and searching for a gene previously implicated in tetronate ring formation, we identified the biosynthetic genes responsible for producing 13-deoxytetrodecamycin (the ted genes). Using the ted cluster in WAC04657 as a reference, we found related clusters in three other organisms: Streptomyces atroolivaceus ATCC 19725, Streptomyces globisporus NRRL B-2293, and Streptomyces sp. strain LaPpAH-202. Comparing the four clusters allowed us to identify the cluster boundaries. Genetic manipulation of the cluster confirmed the involvement of the ted genes in 13-deoxytetrodecamycin biosynthesis and revealed several additional molecules produced through the ted biosynthetic pathway, including tetrodecamycin, dihydrotetrodecamycin, and another, W5.9, a novel molecule. Comparison of the bioactivities of these four molecules suggests that they may act through the covalent modification of their target(s). IMPORTANCEThe tetrodecamycins are a distinct subgroup of the tetronate family of secondary metabolites. Little is known about their biosynthesis or mechanisms of action, making them an attractive subject for investigation. In this paper we present the biosynthetic gene cluster for 13-deoxytetrodecamycin in Streptomyces sp. strain WAC04657. We identify related clusters in several other organisms and show that they produce related molecules.

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Tetrodecadazinone, a novel tetrodecamycin-pyridazinone hybrid with anti-liver fibrosis activity from Streptomyces sp. HU051

Liu

Chen

et al. 2022

Bioorganic Chemistry

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13-Deoxytetrodecamycin, a new tetronate ring-containing antibiotic that is active against multidrug-resistant Staphylococcus aureus

Cited by 7 publications

References 31 publications

Tetrodecamycin: An unusual and interesting tetronate antibiotic

Tetrodecamycin: An unusual and interesting tetronate antibiotic

Biosynthetic Genes for the Tetrodecamycin Antibiotics

Tetrodecadazinone, a novel tetrodecamycin-pyridazinone hybrid with anti-liver fibrosis activity from Streptomyces sp. HU051

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