Improving the productivity of gibberellic acid by combining small-molecule compounds-based targeting technology and transcriptomics analysis in Fusarium fujikuroi

[Display omitted] •A small-molecule compounds-based targeting technology was developed.•Transcriptomic analysis explored the molecular response mechanism of GA3 titer change.•In vivo metabolic engineering and In vitro addition with WCO substrate were adopted.•The engineered strain utilized WCO to ob...

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Bibliographic Details
Published in:Bioresource technology 2024-02, Vol.394, p.130299-130299, Article 130299
Main Authors: Shi, Tian-Qiong, Shen, Yi-hang, Li, Ya-Wen, Huang, Zi-Yi, Nie, Zhi-Kui, Ye, Chao, Wang, Yue-Tong, Guo, Qi
Format: Article
Language:English
Subjects:
biochemical pathways
bioreactors
biosynthesis
carbon
Fusarium fujikuroi
Gibberellic acid
lipids
Metabolic engineering
Small-molecule compounds
squalene
transcriptomics
Transcriptomics analysis
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Summary:[Display omitted] •A small-molecule compounds-based targeting technology was developed.•Transcriptomic analysis explored the molecular response mechanism of GA3 titer change.•In vivo metabolic engineering and In vitro addition with WCO substrate were adopted.•The engineered strain utilized WCO to obtain 3.24 g/L GA3 in a 5 L bioreactor. Gibberellic acid (GA3), produced industrially by Fusarium fujikuroi, stands as a crucial plant growth regulator extensively employed in the agriculture filed while limited understanding of the global metabolic network hinders researchers from conducting rapid targeted modifications. In this study, a small-molecule compounds-based targeting technology was developed to increase GA3 production. Firstly, various small molecules were used to target key nodes of different pathways and the result displayed that supplement of terbinafine improved significantly GA3 accumulation, which reached to 1.08 g/L. Subsequently, lipid and squalene biosynthesis pathway were identified as the key pathways influencing GA3 biosynthesis by transcriptomic analysis. Thus, the strategies including in vivo metabolic engineering modification and in vitro supplementation of lipid substrates were adopted, both contributed to an enhanced GA3 yield. Finally, the engineered strain demonstrated the ability to achieve a GA3 yield of 3.24 g/L in 5 L bioreactor when utilizing WCO as carbon source and feed.
ISSN:0960-8524
1873-2976
DOI:10.1016/j.biortech.2024.130299