Draft Genome Sequence of Streptomyces rapamycinicus Strain NRRL 5491, the Producer of the Immunosuppressant Rapamycin

Baranašić, Damir; Starčević, Antonio; Žučko, Jurica; Blažič, Marko; Horvat, Marinka; Gjuračić, Krešimir; Fujs, Štefan; Hranueli, Daslav; Kosec, Gregor; Cullum, John; Petković, Hrvoje

doi:10.1128/genomea.00581-13

Cited by 40 publications

(29 citation statements)

References 14 publications

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“…Streptomyces niveus NCIMB 11891 (Flinspach et al, 2014) Produces novobiocin, an aminocoumarin antibiotics. Streptomyces rapamycinicus NRRL 5491 (Baranasic et al, 2013) Produces the immunosuppressant drug rapamycin. Streptomyces rimosus ATCC 10970 (Pethick et al, 2013) Oxytetracycline Streptomyces roseochromogenes subsp.…”

Section: Species and Strain Motivation For Sequencingmentioning

confidence: 99%

Recently published Streptomyces genome sequences

Harrison

Studholme

2014

Microbial Biotechnology

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Section: Species and Strain Motivation For Sequencingmentioning

confidence: 99%

Recently published Streptomyces genome sequences

Harrison

Studholme

2014

Microbial Biotechnology

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“…This problem was overcome by the development of a series of cloning vectors, transformation protocol [4] and genetic manipulation which was shown to be possible in this strain [35,40]. As the genome sequence of A. mediterranei S699 [12] and Streptomyces hygroscopicus [41] was available, Nigam et al [4] employed combinatorial biosynthetic approach for the genetic manipulation of rifamycin biosynthetic gene cluster. The acyltransferase (AT) domain of the 6 module (AT6) of the rifamycin polyketide synthase (incorporates propionate) was swapped with the AT domain in the 2 module (AT2) of the rapamycin polyketide synthase (incorporates acetate) gene cluster in A. mediterranei S699.…”

Section: -Desmethylrifamycin B By Genetic Manipulation Of Rifamycinmentioning

confidence: 99%

Genetics and Genomics of the Genus Amycolatopsis

2016

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Actinobacteria are gram-positive filamentous bacteria which contains some of the most deadly human pathogens (Mycobacterium tuberculosis, M. leprae, Corynebacterium diphtheriae, Nocardia farcinica), plant pathogens (Streptomyces scabies, Leifsonia xyli) along with organisms that produces antibiotic (Streptomycetes, Amycolatopsis, Salinospora). Interestingly, these bacteria are equipped with an extraordinary capability of producing antibiotics and other metabolites which have medicinal properties. With the advent of inexpensive genome sequencing techniques and their clinical importance, many genomes of Actinobacteria have been successfully sequenced. These days, with the constant increasing number of drug-resistant bacteria, the urgent need for discovering new antibiotics has emerged as a major scientific challenge. And, unfortunately the traditional method of screening bacterial strains for the production of antibiotics has decreased leading to a paradigm shift in the planning and execution of discovery of novel biosynthetic gene clusters via genome mining process. The entire focus has shifted to the evaluation of genetic capacity of organisms for metabolite production and activation of cryptic gene clusters. This has been made possible only due to the availability of genome sequencing and has been augmented by genomic studies and new biotechnological approaches. Through this article, we present the analysis of the genomes of species belonging to the genus Amycolatopsis, sequenced till date with a focus on completely sequenced genomes and their application for further studies.

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“…To supply accurate gene sequence for analysis of RT-PCR, the target genes of primary metabolism were amplified and sequenced with the primer designed on the basis of genomic sequence of Streptomyces rapamycinicus strain NRRL 5491 [1]. Then, real-time PCR was carried out to detect gene relative transcriptional expression abundance according to the method of Borges et al [2].…”

Section: Gene Transcription Expression Analysis Of Key Enzymes By Reamentioning

confidence: 99%

Comparative metabolic profiling reveals the key role of amino acids metabolism in the rapamycin overproduction by Streptomyces hygroscopicus

Wang

Liu

et al. 2015

Journal of Industrial Microbiology and Biotechnology

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Rapamycin is an important natural macrolide antibiotic with antifungal, immunosuppressive and anticancer activity produced by Streptomyces hygroscopicus. In this study, a mutant strain obtained by ultraviolet mutagenesis displayed higher rapamycin production capacity compared to the wild-type S. hygroscopicus ATCC 29253. To gain insights into the mechanism of rapamycin overproduction, comparative metabolic profiling between the wild-type and mutant strain was performed. A total of 86 metabolites were identified by gas chromatography-mass spectrometry. Pattern recognition methods, including principal component analysis, partial least squares and partial least squares discriminant analysis, were employed to determine the key biomarkers. The results showed that 22 potential biomarkers were closely associated with the increase of rapamycin production and the tremendous metabolic difference was observed between the two strains. Furthermore, metabolic pathway analysis revealed that amino acids metabolism played an important role in the synthesis of rapamycin, especially lysine, valine, tryptophan, isoleucine, glutamate, arginine and ornithine. The inadequate supply of amino acids, or namely "nitrogen starvation" occurred in the mutant strain. Subsequently, the exogenous addition of amino acids into the fermentation medium of the mutant strain confirmed the above conclusion, and rapamycin production of the mutant strain increased to 426.7 mg/L after adding lysine, approximately 5.8-fold of that in the wild-type strain. Finally, the results of real-time PCR and enzyme activity assays demonstrated that dihydrodipicolinate synthase involved with lysine metabolism played vital role in the biosynthesis of rapamycin. These findings will provide a theoretical basis for further improving production of rapamycin.

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Draft Genome Sequence of Streptomyces rapamycinicus Strain NRRL 5491, the Producer of the Immunosuppressant Rapamycin

Abstract: Streptomyces rapamycinicus strain NRRL 5491 produces the important drug rapamycin. It has a large genome of 12.7 Mb, of which over 3 Mb consists of 48 secondary metabolite biosynthesis clusters.

Cited by 40 publications

References 14 publications

Recently published Streptomyces genome sequences

Recently published Streptomyces genome sequences

Genetics and Genomics of the Genus Amycolatopsis

Comparative metabolic profiling reveals the key role of amino acids metabolism in the rapamycin overproduction by Streptomyces hygroscopicus

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