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Combinatorial Metabolic Engineering for Enhanced Gibberellic Acid Biosynthesis in Fusarium fujikuroi

Year: 2025

Type: article

Abstract: ABSTRACT Gibberellic 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.

Source: Biotechnology and Bioengineering

DOI: 10.1002/bit.29005

Authors: Xia Ke, Yao Chen, Rui Jia, Hao‐Nan Wang, Zhi‐Qiang Liu, Yu‐Guo Zheng

Institution: Zhejiang University of Technology

Language: English

Topic: Microbial Metabolic Engineering and Bioproduction

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Zero hunger

Open Access status: bronze

Funders: National Natural Science Foundation of China, National Key Research and Development Program of China, Natural Science Foundation of Zhejiang Province