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Aspergillus niger is a superior expression host for the production of bioactive fungal cyclodepsipeptides

Overview of attention for article published in Fungal Biology and Biotechnology, March 2018
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Title
Aspergillus niger is a superior expression host for the production of bioactive fungal cyclodepsipeptides
Published in
Fungal Biology and Biotechnology, March 2018
DOI 10.1186/s40694-018-0048-3
Pubmed ID
Authors

Simon Boecker, Stefan Grätz, Dennis Kerwat, Lutz Adam, David Schirmer, Lennart Richter, Tabea Schütze, Daniel Petras, Roderich D. Süssmuth, Vera Meyer

Abstract

Fungal cyclodepsipeptides (CDPs) are non-ribosomally synthesized peptides produced by a variety of filamentous fungi and are of interest to the pharmaceutical industry due to their anticancer, antimicrobial and anthelmintic bioactivities. However, both chemical synthesis and isolation of CDPs from their natural producers are limited due to high costs and comparatively low yields. These challenges might be overcome by heterologous expression of the respective CDP-synthesizing genes in a suitable fungal host. The well-established industrial fungus Aspergillus niger was recently genetically reprogrammed to overproduce the cyclodepsipeptide enniatin B in g/L scale, suggesting that it can generally serve as a high production strain for natural products such as CDPs. In this study, we thus aimed to determine whether other CDPs such as beauvericin and bassianolide can be produced with high titres in A. niger, and whether the generated expression strains can be used to synthesize new-to-nature CDP derivatives. The beauvericin and bassianolide synthetases were expressed under control of the tuneable Tet-on promoter, and titres of about 350-600 mg/L for bassianolide and beauvericin were achieved when using optimized feeding conditions, respectively. These are the highest concentrations ever reported for both compounds, whether isolated from natural or heterologous expression systems. We also show that the newly established Tet-on based expression strains can be used to produce new-to-nature beauvericin derivatives by precursor directed biosynthesis, including the compounds 12-hydroxyvalerate-beauvericin and bromo-beauvericin. By feeding deuterated variants of one of the necessary precursors (d-hydroxyisovalerate), we were able to purify deuterated analogues of beauvericin and bassianolide from the respective A. niger expression strains. These deuterated compounds could potentially be used as internal standards in stable isotope dilution analyses to evaluate and quantify fungal spoilage of food and feed products. In this study, we show that the product portfolio of A. niger can be expanded from enniatin to other CDPs such as beauvericin and bassianolide, as well as derivatives thereof. This illustrates the capability of A. niger to produce a range of different peptide natural products in titres high enough to become industrially relevant.

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The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 66 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 66 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 17 26%
Researcher 10 15%
Student > Bachelor 7 11%
Student > Master 6 9%
Lecturer 2 3%
Other 5 8%
Unknown 19 29%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 22 33%
Agricultural and Biological Sciences 14 21%
Engineering 3 5%
Chemistry 2 3%
Nursing and Health Professions 1 2%
Other 2 3%
Unknown 22 33%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 09 July 2019.
All research outputs
#13,037,417
of 23,508,125 outputs
Outputs from Fungal Biology and Biotechnology
#84
of 148 outputs
Outputs of similar age
#156,697
of 332,534 outputs
Outputs of similar age from Fungal Biology and Biotechnology
#4
of 7 outputs
Altmetric has tracked 23,508,125 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 148 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.9. This one is in the 40th percentile – i.e., 40% 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 332,534 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 7 others from the same source and published within six weeks on either side of this one. This one has scored higher than 3 of them.