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Overexpression of a type III PKS gene affording novel violapyrones with enhanced anti-influenza A virus activity

Overview of attention for article published in Microbial Cell Factories, April 2018
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About this Attention Score

  • Above-average Attention Score compared to outputs of the same age (52nd percentile)

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4 tweeters

Citations

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8 Dimensions

Readers on

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15 Mendeley
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Title
Overexpression of a type III PKS gene affording novel violapyrones with enhanced anti-influenza A virus activity
Published in
Microbial Cell Factories, April 2018
DOI 10.1186/s12934-018-0908-9
Pubmed ID
Authors

Lukuan Hou, Huiming Huang, Huayue Li, Shuyao Wang, Jianhua Ju, Wenli Li

Abstract

Type III polyketide synthases (PKSs) are simple homodimer ketosynthases that distribute across plants, fungi, and bacteria, catalyzing formation of pyrone- and resorcinol-types aromatic polyketides with various bioactivities. The broad substrate promiscuity displayed by type III PKSs makes them wonderful candidates for expanding chemical diversity of polyketides. Violapyrone B (VLP B, 10), an α-pyrone compound produced by deepsea-derived Streptomyces somaliensis SCSIO ZH66, is encoded by a type III PKS VioA. We overexpressed VioA in three different hosts, including Streptomyces coelicolor M1146, Streptomyces sanyensis FMA as well as the native producer S. somaliensis SCSIO ZH66, leading to accumulation of different violapyrone compounds. Among them, S. coelicolor M1146 served as the host producing the most abundant violapyrones, from which five new (2-4, 7 and 12) and nine known (1, 5, 6, 8-11, 13 and 14) compounds were identified. Anti-influenza A (H1N1) virus activity of these compounds was then evaluated using ribavirin as a positive control (IC50 = 112.9 μM), revealing that compounds 11-14 showed considerable activity with IC50 values of 112.7, 26.9, 106.7 and 28.8 μM, respectively, which are significantly improved as compared to that of VLP B (10) (IC50 > 200 μM). The productions of 10 and 13 were increased by adding P450 inhibitor metyrapone. In addition, site-directed mutagenesis experiment led to demonstration of the residue S242 to be essential for the activity of VioA. Biological background of the expression hosts is an important factor impacting on the encoding products of type III PKSs. By using S. coelicolor M1146 as cell factory, we were able to generate fourteen VLPs compounds. Anti-H1N1 activity assay suggested that the lipophilic nature of the alkyl chains of VLPs plays an important role for the activity, providing valuable guidance for further structural optimization of VLPs.

Twitter Demographics

The data shown below were collected from the profiles of 4 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 15 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 15 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 5 33%
Student > Master 4 27%
Student > Ph. D. Student 2 13%
Student > Bachelor 1 7%
Unknown 3 20%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 4 27%
Agricultural and Biological Sciences 3 20%
Medicine and Dentistry 3 20%
Engineering 1 7%
Unknown 4 27%

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 16 April 2018.
All research outputs
#6,934,964
of 12,808,036 outputs
Outputs from Microbial Cell Factories
#431
of 935 outputs
Outputs of similar age
#123,266
of 271,476 outputs
Outputs of similar age from Microbial Cell Factories
#1
of 1 outputs
Altmetric has tracked 12,808,036 research outputs across all sources so far. This one is in the 44th percentile – i.e., 44% of other outputs scored the same or lower than it.
So far Altmetric has tracked 935 research outputs from this source. They receive a mean Attention Score of 3.7. This one has gotten more attention than average, scoring higher than 52% of its peers.
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 271,476 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 52% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them