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Characterization and engineering of the biosynthesis gene cluster for antitumor macrolides PM100117 and PM100118 from a marine actinobacteria: generation of a novel improved derivative

Overview of attention for article published in Microbial Cell Factories, February 2016
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2 X users
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39 Mendeley
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Title
Characterization and engineering of the biosynthesis gene cluster for antitumor macrolides PM100117 and PM100118 from a marine actinobacteria: generation of a novel improved derivative
Published in
Microbial Cell Factories, February 2016
DOI 10.1186/s12934-016-0443-5
Pubmed ID
Authors

Raúl García Salcedo, Carlos Olano, Cristina Gómez, Rogelio Fernández, Alfredo F. Braña, Carmen Méndez, Fernando de la Calle, José A. Salas

Abstract

PM100117 and PM100118 are glycosylated polyketides with remarkable antitumor activity, which derive from the marine symbiotic actinobacteria Streptomyces caniferus GUA-06-05-006A. Structurally, PM100117 and PM100118 are composed of a macrocyclic lactone, three deoxysugar units and a naphthoquinone (NQ) chromophore that shows a clear structural similarity to menaquinone. Whole-genome sequencing of S. caniferus GUA-06-05-006A has enabled the identification of PM100117 and PM100118 biosynthesis gene cluster, which has been characterized on the basis of bioinformatics and genetic engineering data. The product of four genes shows high identity to proteins involved in the biosynthesis of menaquinone via futalosine. Deletion of one of these genes led to a decay in PM100117 and PM100118 production, and to the accumulation of several derivatives lacking NQ. Likewise, five additional genes have been genetically characterized to be involved in the biosynthesis of this moiety. Moreover, the generation of a mutant in a gene coding for a putative cytochrome P450 has led to the production of PM100117 and PM100118 structural analogues showing an enhanced in vitro cytotoxic activity relative to the parental products. Although a number of compounds structurally related to PM100117 and PM100118 has been discovered, this is, to our knowledge, the first insight reported into their biosynthesis. The structural resemblance of the NQ moiety to menaquinone, and the presence in the cluster of four putative menaquinone biosynthetic genes, suggests a connection between the biosynthesis pathways of both compounds. The availability of the PM100117 and PM100118 biosynthetic gene cluster will surely pave a way to the combinatorial engineering of more derivatives.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Japan 1 3%
Germany 1 3%
Unknown 37 95%

Demographic breakdown

Readers by professional status Count As %
Researcher 11 28%
Student > Ph. D. Student 8 21%
Student > Master 5 13%
Student > Postgraduate 4 10%
Student > Bachelor 3 8%
Other 3 8%
Unknown 5 13%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 14 36%
Agricultural and Biological Sciences 10 26%
Chemistry 3 8%
Pharmacology, Toxicology and Pharmaceutical Science 1 3%
Computer Science 1 3%
Other 4 10%
Unknown 6 15%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 November 2016.
All research outputs
#13,463,735
of 22,858,915 outputs
Outputs from Microbial Cell Factories
#820
of 1,603 outputs
Outputs of similar age
#143,214
of 298,745 outputs
Outputs of similar age from Microbial Cell Factories
#14
of 34 outputs
Altmetric has tracked 22,858,915 research outputs across all sources so far. This one is in the 39th percentile – i.e., 39% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,603 research outputs from this source. They receive a mean Attention Score of 4.4. This one is in the 47th percentile – i.e., 47% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 298,745 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.
We're also able to compare this research output to 34 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.