4.5 Article

Investigation of the enhancement for Echinocandin B fermentation with methyl oleate from transcription level

Journal

BIOPROCESS AND BIOSYSTEMS ENGINEERING
Volume 46, Issue 7, Pages 1045-1052

Publisher

SPRINGER
DOI: 10.1007/s00449-023-02883-4

Keywords

Echinocandin B; Methyl oleate; Precursor amino acids; Transcription level analysis

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The effects of different amino acids on Echinocandin B biosynthesis were investigated. It was found that adding L-threonine did not significantly increase the fermentation titer of Echinocandin B. However, using methyl oleate as a carbon source resulted in a two-fold increase in Echinocandin B production. Transcription level analysis indicated that the gene an655543 related to L-threonine biosynthesis had high expression during fermentation, suggesting that exogenous addition of L-threonine had minimal impact. Additionally, the transcription level of gene ecdA appeared to be the main limiting factor for Echinocandin B biosynthesis. This study provides a foundation for future modifications of Echinocandin B-producing strains.
Echinocandin B (ECB) is the key precursor compound of the antifungal drug Anidulafungin. The effects of the five precursor amino acids on ECB biosynthesis were firstly investigated. It showed that although L-threonine was a main compound of the hexapeptide scaffold of ECB, exogenous addition of L-threonine had no significant effect on the increase of ECB fermentation titer. Meanwhile, the ECB fermentation titer with methyl oleate showed two times higher than that of the other carbon sources. Transcription level analysis of the key genes for ECB biosynthesis indicated that the gene an655543 related to L-threonine biosynthesis showed higher value during the fermentation process, therefore, the exogenous addition of L-threonine had no obvious affection. Furthermore, it indicated that the transcription level of gene ecdA might be the main restriction factor for the ECB biosynthesis. The study provided the research foundation for the modification of the ECB producing strains in the following work.

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