Tailored biosynthesis of gibberellin plant hormones in yeast

The application of small amounts of natural plant growth hormones, such as gibberellins (GAs), can increase the productivity and quality of many vegetable and fruit crops. However, gibberellin growth hormones usage is limited by the high cost of their production, which is currently based on fermenta...

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Veröffentlicht in:Metabolic engineering 2021-07, Vol.66, p.1-11
Hauptverfasser: Kildegaard, Kanchana R., Arnesen, Jonathan A., Adiego-Pérez, Belén, Rago, Daniela, Kristensen, Mette, Klitgaard, Andreas K., Hansen, Esben H., Hansen, Jørgen, Borodina, Irina
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Sprache:eng
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Zusammenfassung:The application of small amounts of natural plant growth hormones, such as gibberellins (GAs), can increase the productivity and quality of many vegetable and fruit crops. However, gibberellin growth hormones usage is limited by the high cost of their production, which is currently based on fermentation of a natural fungal producer Fusarium fujikuroi that produces a mix of several GAs. We explored the potential of the oleaginous yeast Yarrowia lipolytica to produce specific profiles of GAs. Firstly, the production of the GA-precursor ent-kaurenoic acid (KA) at 3.75 mg/L was achieved by expression of biosynthetic enzymes from the plant Arabidopsis thaliana and upregulation of the mevalonate (MVA) pathway. We then built a GA4-producing strain by extending the GA-biosynthetic pathway and upregulating the MVA-pathway further, resulting in 17.29 mg/L GA4. Additional expression of the F. fujikoroi GA-biosynthetic enzymes resulted in the production of GA7 (trace amounts) and GA3 (2.93 mg/L). Lastly, through protein engineering and the expression of additional KA-biosynthetic genes, we increased the GA3-production 4.4-fold resulting in 12.81 mg/L. The developed system presents a promising resource for the recombinant production of specific gibberellins, identifying bottlenecks in GA biosynthesis, and discovering new GA biosynthetic genes. Biological Sciences, Applied Biological Sciences. •A complete biosynthetic pathway towards gibberellins was reconstructed in a microbial host•The pathway towards ent-kaurenoic acid consisted of Arabidopsis thaliana enzymes•The pathway from ent-kaurenoic acid to gibberellins GA3, GA4 and GA7 consisted of Fusarium fujikuroi enzymes•Y. lipolytica expressed 14 heterologous genes for gibberellins biosynthesis and had 5 genome edits for improved mevalonate flux•The strains produced up to 12 mg/L of GA3 and up to 17 mg/L GA4 in small-scale cultivations
ISSN:1096-7176
1096-7184
DOI:10.1016/j.ymben.2021.03.010