Giant linear plasmids in Streptomyces: a treasure trove of antibiotic biosynthetic clusters

Kinashi, Haruyasu

doi:10.1038/ja.2010.146

Cited by 45 publications

(37 citation statements)

References 76 publications

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“…In this respect, it is interesting to mention that spreading of this type of biosynthetic gene clusters between different microorganisms could be partly favored by the fact that some gene clusters coding for bisintercalator compounds are chromosomally encoded, but others are present in giant plasmids: the 520 kb pKSL plasmid from S. lasaliensis contains the echinomycin gene cluster [10,11]. …”

Section: Antitumor Compounds From the Bisintercalators Family: Thementioning

confidence: 99%

Biosynthetic Modularity Rules in the Bisintercalator Family of Antitumor Compounds

et al. 2014

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Diverse actinomycetes produce a family of structurally and biosynthetically related non-ribosomal peptide compounds which belong to the chromodepsipeptide family. These compounds act as bisintercalators into the DNA helix. They give rise to antitumor, antiparasitic, antibacterial and antiviral bioactivities. These compounds show a high degree of conserved modularity (chromophores, number and type of amino acids). This modularity and their high sequence similarities at the genetic level imply a common biosynthetic origin for these pathways. Here, we describe insights about rules governing this modular biosynthesis, taking advantage of the fact that nowadays five of these gene clusters have been made public (thiocoraline, triostin, SW-163 and echinomycin/quinomycin). This modularity has potential application for designing and producing novel genetic engineered derivatives, as well as for developing new chemical synthesis strategies. These would facilitate their clinical development.

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Section: Antitumor Compounds From the Bisintercalators Family: Thementioning

confidence: 99%

Biosynthetic Modularity Rules in the Bisintercalator Family of Antitumor Compounds

et al. 2014

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“…Recent findings that subinhibitory concentrations of antibiotics drastically affect transcriptional profiles of exposed bacteria supports this hypothesis [7], [8], and prompts further studies on the true roles of secondary metabolites and evolution of their biosynthetic pathways. In particular, it would be interesting to trace acquisition of new biosynthetic gene clusters by marine actinomycetes, and to study the mechanism behind their transfer, which is likely to be mediated by mobile genetic elements [9]. Although a relatively large number of actinomycetes have been isolated from marine environments, including sponges [10]–[12], only a few studies report on their genomes and biosynthetic gene clusters [13]–[15].…”

Section: Introductionmentioning

confidence: 99%

Genomics of Sponge-Associated Streptomyces spp. Closely Related to Streptomyces albus J1074: Insights into Marine Adaptation and Secondary Metabolite Biosynthesis Potential

et al. 2014

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A total of 74 actinomycete isolates were cultivated from two marine sponges, Geodia barretti and Phakellia ventilabrum collected at the same spot at the bottom of the Trondheim fjord (Norway). Phylogenetic analyses of sponge-associated actinomycetes based on the 16S rRNA gene sequences demonstrated the presence of species belonging to the genera Streptomyces, Nocardiopsis, Rhodococcus, Pseudonocardia and Micromonospora. Most isolates required sea water for growth, suggesting them being adapted to the marine environment. Phylogenetic analysis of Streptomyces spp. revealed two isolates that originated from different sponges and had 99.7% identity in their 16S rRNA gene sequences, indicating that they represent very closely related strains. Sequencing, annotation, and analyses of the genomes of these Streptomyces isolates demonstrated that they are sister organisms closely related to terrestrial Streptomyces albus J1074. Unlike S. albus J1074, the two sponge streptomycetes grew and differentiated faster on the medium containing sea water. Comparative genomics revealed several genes presumably responsible for partial marine adaptation of these isolates. Genome mining targeted to secondary metabolite biosynthesis gene clusters identified several of those, which were not present in S. albus J1074, and likely to have been retained from a common ancestor, or acquired from other actinomycetes. Certain genes and gene clusters were shown to be differentially acquired or lost, supporting the hypothesis of divergent evolution of the two Streptomyces species in different sponge hosts.

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“…Unlike circular plasmids, linear plasmids are rarely observed in lactobacilli [12] but often confer advantageous phenotypes to their hosts [19, 20] and have been extensively studied in Streptomyces [21, 22], Borrelia [23] and Bacillus [24]. Linear phage genomes are also harboured by strains of Escherichia coli [25], Yersinia enterocolitica [26], Klebsiella oxytoca [27] as well as the probiotic cheese strain Lactobacillus paracasei NFBC 338 [28].…”

Section: Introductionmentioning

confidence: 99%

Unusual genome complexity in Lactobacillus salivarius JCM1046

et al. 2014

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BackgroundLactobacillus salivarius strains are increasingly being exploited for their probiotic properties in humans and animals. Dissemination of antibiotic resistance genes among species with food or probiotic-association is undesirable and is often mediated by plasmids or integrative and conjugative elements. L. salivarius strains typically have multireplicon genomes including circular megaplasmids that encode strain-specific traits for intestinal survival and probiotic activity. Linear plasmids are less common in lactobacilli and show a very limited distribution in L. salivarius. Here we present experimental evidence that supports an unusually complex multireplicon genome structure in the porcine isolate L. salivarius JCM1046.ResultsJCM1046 harbours a 1.83 Mb chromosome, and four plasmids which constitute 20% of the genome. In addition to the known 219 kb repA-type megaplasmid pMP1046A, we identified and experimentally validated the topology of three additional replicons, the circular pMP1046B (129 kb), a linear plasmid pLMP1046 (101 kb) and pCTN1046 (33 kb) harbouring a conjugative transposon. pMP1046B harbours both plasmid-associated replication genes and paralogues of chromosomally encoded housekeeping and information-processing related genes, thus qualifying it as a putative chromid. pLMP1046 shares limited sequence homology or gene synteny with other L. salivarius plasmids, and its putative replication-associated protein is homologous to the RepA/E proteins found in the large circular megaplasmids of L. salivarius. Plasmid pCTN1046 harbours a single copy of an integrated conjugative transposon (Tn6224) which appears to be functionally intact and includes the tetracycline resistance gene tetM.ConclusionExperimental validation of sequence assemblies and plasmid topology resolved the complex genome architecture of L. salivarius JCM1046. A high-coverage draft genome sequence would not have elucidated the genome complexity in this strain. Given the expanding use of L. salivarius as a probiotic, it is important to determine the genotypic and phenotypic organization of L. salivarius strains. The identification of Tn6224-like elements in this species has implications for strain selection for probiotic applications.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-771) contains supplementary material, which is available to authorized users.

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Giant linear plasmids in Streptomyces: a treasure trove of antibiotic biosynthetic clusters

Cited by 45 publications

References 76 publications

Biosynthetic Modularity Rules in the Bisintercalator Family of Antitumor Compounds

Biosynthetic Modularity Rules in the Bisintercalator Family of Antitumor Compounds

Genomics of Sponge-Associated Streptomyces spp. Closely Related to Streptomyces albus J1074: Insights into Marine Adaptation and Secondary Metabolite Biosynthesis Potential

Unusual genome complexity in Lactobacillus salivarius JCM1046

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