Combinatorial Metabolic Engineering for Enhanced Gibberellic Acid Biosynthesis in Fusarium fujikuroi

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Auteurs principaux: Xia Ke, Yao Chen, Rui Jia, Hao‐Nan Wang, Zhi‐Qiang Liu, Yu‐Guo Zheng
Format: Artículo Open Access
Publié: Wiley 2025
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author Xia Ke
Yao Chen
Rui Jia
Hao‐Nan Wang
Zhi‐Qiang Liu
Yu‐Guo Zheng
author_facet Xia Ke
Yao Chen
Rui Jia
Hao‐Nan Wang
Zhi‐Qiang Liu
Yu‐Guo Zheng
Xia Ke
Yao Chen
Rui Jia
Hao‐Nan Wang
Zhi‐Qiang Liu
Yu‐Guo Zheng
collection Wiley Open Access
contents Combinatorial Metabolic Engineering for Enhanced Gibberellic Acid Biosynthesis in Fusarium fujikuroi Xia Ke Yao Chen Rui Jia Hao‐Nan Wang Zhi‐Qiang Liu Yu‐Guo Zheng Biotechnology and Bioengineering ABSTRACTGibberellic acid (GA3), a quintessential diterpenoid phytohormone, is indispensable in agronomic practices, horticulture, and the wine industry. This study implemented a combinatorial metabolic engineering strategy within Fusarium fujikuroi (F. fujikuroi) by integrating the potentiation of global regulatory factors (GRFs), and amplification of biosynthetic precursors, alongside dynamic modulation of cofactors with dissolved oxygen supply, to precisely enhance GA3 biosynthesis. Transcriptomic analyses revealed that positive GRFs (AreB, Hat1, and Ada3) enhanced carbon and nitrogen metabolism, increased biomass accumulation, and upregulated transcription levels of the GA3 biosynthetic gene cluster. The use of endogenous nitrogen‐responsive promoters ensured a balanced supply of cofactors and oxygen, thereby preventing the accumulation of terpenoid by‐products. These combinatorial metabolic engineering strategies presented in this study make a significant step toward the enhancement of GA3 yield (3.22 g/L) via submerged fermentation of F. fujikuroi, offering novel insights to enable high‐level biosynthesis of secondary metabolites in fungal chassis. 10.1002/bit.29005 http://onlinelibrary.wiley.com/termsAndConditions#vor
doi_str_mv 10.1002/bit.29005
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institution Wiley Open Access
license_str_mv http://onlinelibrary.wiley.com/termsAndConditions#vor
publishDate 2025
publisher Wiley
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spellingShingle Combinatorial Metabolic Engineering for Enhanced Gibberellic Acid Biosynthesis in Fusarium fujikuroi
Xia Ke
Yao Chen
Rui Jia
Hao‐Nan Wang
Zhi‐Qiang Liu
Yu‐Guo Zheng
Biotechnology and Bioengineering
Combinatorial Metabolic Engineering for Enhanced Gibberellic Acid Biosynthesis in Fusarium fujikuroi Xia Ke Yao Chen Rui Jia Hao‐Nan Wang Zhi‐Qiang Liu Yu‐Guo Zheng Biotechnology and Bioengineering ABSTRACTGibberellic acid (GA3), a quintessential diterpenoid phytohormone, is indispensable in agronomic practices, horticulture, and the wine industry. This study implemented a combinatorial metabolic engineering strategy within Fusarium fujikuroi (F. fujikuroi) by integrating the potentiation of global regulatory factors (GRFs), and amplification of biosynthetic precursors, alongside dynamic modulation of cofactors with dissolved oxygen supply, to precisely enhance GA3 biosynthesis. Transcriptomic analyses revealed that positive GRFs (AreB, Hat1, and Ada3) enhanced carbon and nitrogen metabolism, increased biomass accumulation, and upregulated transcription levels of the GA3 biosynthetic gene cluster. The use of endogenous nitrogen‐responsive promoters ensured a balanced supply of cofactors and oxygen, thereby preventing the accumulation of terpenoid by‐products. These combinatorial metabolic engineering strategies presented in this study make a significant step toward the enhancement of GA3 yield (3.22 g/L) via submerged fermentation of F. fujikuroi, offering novel insights to enable high‐level biosynthesis of secondary metabolites in fungal chassis. 10.1002/bit.29005 http://onlinelibrary.wiley.com/termsAndConditions#vor
title Combinatorial Metabolic Engineering for Enhanced Gibberellic Acid Biosynthesis in Fusarium fujikuroi
topic Biotechnology and Bioengineering
url https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/bit.29005