Insights into the Evolution of Macrolactam Biosynthesis through Cloning and Comparative Analysis of the Biosynthetic Gene Cluster for a Novel Macrocyclic Lactam, ML-449

Jørgensen, H. E.; Degnes, Kristin F.; Dikiy, Alexander; Fjærvik, Espen; Klinkenberg, Geir; Zotchev, Sergey B.

doi:10.1128/aem.00744-09

Cited by 67 publications

(69 citation statements)

References 46 publications

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“…TFRs are also present in the biosynthesis clusters for diverse polyketides, including ansamycins (e.g., rifQ in the rifamycin cluster [91]), macrolactams (e.g., mlaM in the ML-449 cluster [92]), and polyether ionophores (e.g., schR3 in the calcimycin cluster [93]). TFRs are not limited to polyketide biosynthesis clusters but are found in biosynthesis clusters for nonribosomal peptides (e.g., acmP and acmU in the actinomycin cluster [94]) and nucleoside antibiotics (e.g., amiP in the amicetin cluster [95]).…”

Section: Tfrs Regulating Self-resistance In Antibiotic-producing Orgamentioning

confidence: 99%

The TetR Family of Regulators

Cuthbertson

Nodwell

2013

Microbiol Mol Biol Rev

467

512

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SUMMARY The most common prokaryotic signal transduction mechanisms are the one-component systems in which a single polypeptide contains both a sensory domain and a DNA-binding domain. Among the >20 classes of one-component systems, the TetR family of regulators (TFRs) are widely associated with antibiotic resistance and the regulation of genes encoding small-molecule exporters. However, TFRs play a much broader role, controlling genes involved in metabolism, antibiotic production, quorum sensing, and many other aspects of prokaryotic physiology. There are several well-established model systems for understanding these important proteins, and structural studies have begun to unveil the mechanisms by which they bind DNA and recognize small-molecule ligands. The sequences for more than 200,000 TFRs are available in the public databases, and genomics studies are identifying their target genes. Three-dimensional structures have been solved for close to 200 TFRs. Comparison of these structures reveals a common overall architecture of nine conserved α helices. The most important open question concerning TFR biology is the nature and diversity of their ligands and how these relate to the biochemical processes under their control.

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Section: Tfrs Regulating Self-resistance In Antibiotic-producing Orgamentioning

confidence: 99%

The TetR Family of Regulators

Cuthbertson

Nodwell

2013

Microbiol Mol Biol Rev

467

512

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“…The first step consisted of agar diffusion assays using M. luteus ATCC 9341 and C. albicans ATCC 10231 as bacterial and fungal indicator organisms. Inoculums of M. luteus were prepared by growing the bacteria in AM1 medium (17) to an optical density at 600 nm (OD 600 ) of 5.0 (SpectraMaxPlus 384 ; Molecular Devices). Sterile glycerol was added to a final concentration of 10%, and the culture was stored in aliquots at Ϫ80°C.…”

Section: Methodsmentioning

confidence: 99%

Production of a New Thiopeptide Antibiotic, TP-1161, by a Marine Nocardiopsis Species

Engelhardt

Degnes

Kemmler³

et al. 2010

Appl Environ Microbiol

Self Cite

153

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Twenty-seven marine sediment-and sponge-derived actinomycetes with a preference for or dependence on seawater for growth were classified at the genus level using molecular taxonomy. Their potential to produce bioactive secondary metabolites was analyzed by PCR screening for genes involved in polyketide and nonribosomal peptide antibiotic synthesis. Using microwell cultures, conditions for the production of antibacterial and antifungal compounds were identified for 15 of the 27 isolates subjected to this screening. Nine of the 15 active extracts were also active against multiresistant Gram-positive bacterial and/or fungal indicator organisms, including vancomycin-resistant Enterococcus faecium and multidrug-resistant Candida albicans. Activityguided fractionation of fermentation extracts of isolate TFS65-07, showing strong antibacterial activity and classified as a Nocardiopsis species, allowed the identification and purification of the active compound. Structure elucidation revealed this compound to be a new thiopeptide antibiotic with a rare aminoacetone moiety. The in vitro antibacterial activity of this thiopeptide, designated TP-1161, against a panel of bacterial strains was determined.

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“…Macrocyclic lactams have been widely found in nature; [1] these molecules are characteristic in terms of their structure, in which a hydrophilic cluster is present in the macrocyclic skeleton, especially at a remote site from an amide group (Figure 1). There are two subgroups that belong to the family of macrocyclic lactams: the first contains a sugar moiety and the other contains only hydroxy groups.…”

Section: Introductionmentioning

confidence: 99%

“…Vicenistatin (1), which is a conjugate of vicenisamine and vicenilactam, was first isolated in 1993 by Shindo et al from the culture broth of Streptomyces sp. HC34.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Structure–Activity Relationship of Vicenistatin, a Cytotoxic 20‐Membered Macrolactam Glycoside

Fukuda

Nishiyama

Nakamura

et al. 2012

Chemistry An Asian Journal

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We have developed two syntheses of vicenistatin and its analogues. Our first-generation strategy included the rapid and sequential assembly of the macrocyclic lactam by using an intermolecular Horner-Wadsworth-Emmons reaction between the C3-C13 fragment and the C1-C2, C14-C19 fragment, followed by an intramolecular Stille coupling reaction. The second-generation strategy utilized a ring-closing metathesis of a hexaene intermediate to generate the desired 20-membered macrolactam. This second-generation strategy made it possible to prepare synthetic analogues of vicenistatin, including the C20- and/or C23-demethyl analogues. Evaluation of the cytotoxic effect of these analogues indicated the importance of the fixed conformation of aglycon for determining the biological activity of the vicenistatins.

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Insights into the Evolution of Macrolactam Biosynthesis through Cloning and Comparative Analysis of the Biosynthetic Gene Cluster for a Novel Macrocyclic Lactam, ML-449

Cited by 67 publications

References 46 publications

The TetR Family of Regulators

The TetR Family of Regulators

Production of a New Thiopeptide Antibiotic, TP-1161, by a Marine Nocardiopsis Species

Synthesis and Structure–Activity Relationship of Vicenistatin, a Cytotoxic 20‐Membered Macrolactam Glycoside

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