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Improving the production of the micafungin precursor FR901379 in an industrial production strain

Overview of attention for article published in Microbial Cell Factories, March 2023
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Title
Improving the production of the micafungin precursor FR901379 in an industrial production strain
Published in
Microbial Cell Factories, March 2023
DOI 10.1186/s12934-023-02050-0
Pubmed ID
Authors

Ping Men, Yu Zhou, Li Xie, Xuan Zhang, Wei Zhang, Xuenian Huang, Xuefeng Lu

Abstract

Micafungin is an echinocandin-type antifungal agent used for the clinical treatment of invasive fungal infections. It is semisynthesized from the sulfonated lipohexapeptide FR901379, a nonribosomal peptide produced by the filamentous fungus Coleophoma empetri. However, the low fermentation efficiency of FR901379 increases the cost of micafungin production and hinders its widespread clinical application. Here, a highly efficient FR901379-producing strain was constructed via systems metabolic engineering in C. empetri MEFC09. First, the biosynthesis pathway of FR901379 was optimized by overexpressing the rate-limiting enzymes cytochrome P450 McfF and McfH, which successfully eliminated the accumulation of unwanted byproducts and increased the production of FR901379. Then, the functions of putative self-resistance genes encoding β-1,3-glucan synthase were evaluated in vivo. The deletion of CEfks1 affected growth and resulted in more spherical cells. Additionally, the transcriptional activator McfJ for the regulation of FR901379 biosynthesis was identified and applied in metabolic engineering. Overexpressing mcfJ markedly increased the production of FR901379 from 0.3 g/L to 1.3 g/L. Finally, the engineered strain coexpressing mcfJ, mcfF, and mcfH was constructed for additive effects, and the FR901379 titer reached 4.0 g/L under fed-batch conditions in a 5 L bioreactor. This study represents a significant improvement for the production of FR901379 and provides guidance for the establishment of efficient fungal cell factories for other echinocandins.

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Mendeley readers

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The data shown below were compiled from readership statistics for 7 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 7 100%

Demographic breakdown

Readers by professional status Count As %
Unspecified 1 14%
Student > Ph. D. Student 1 14%
Unknown 5 71%
Readers by discipline Count As %
Unspecified 1 14%
Agricultural and Biological Sciences 1 14%
Unknown 5 71%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 07 March 2023.
All research outputs
#16,571,845
of 24,380,426 outputs
Outputs from Microbial Cell Factories
#1,073
of 1,719 outputs
Outputs of similar age
#236,362
of 408,402 outputs
Outputs of similar age from Microbial Cell Factories
#14
of 33 outputs
Altmetric has tracked 24,380,426 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,719 research outputs from this source. They receive a mean Attention Score of 4.8. This one is in the 28th percentile – i.e., 28% 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 408,402 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 33 others from the same source and published within six weeks on either side of this one. This one is in the 33rd percentile – i.e., 33% of its contemporaries scored the same or lower than it.