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- W4289829536 abstract "The oxidized kaurene (Ox-Kau) compounds are the core structures of many important diterpenoids with biological activities and economical values. However, easy access to diverse Ox-Kau products is still limited by low natural abundance, and large-scale manufacture remain challenging due to lack of proper heterologous production. To achieve an abundant source alternative to natural extracts, we here report a highly effective Escherichia coli-based platform for the de novo production of multiple Ox-Kau molecules from simple carbon source. Pathway optimization in prokaryotic cells through modification of transmembrane CYP450 oxidases, cytochrome b5 co-expression and AlphaFold-based protein engineering improved a 50-fold yield of steviol (1.07 g L−1), a key intermediate in the kaurenoid biosynthesis. Combinatorial biosynthetic strategy further led to a series of oxidized derivatives (20–600 mg L−1) with rich oxygenated functional groups on C3, C7, C16 and C19 previously hard to be introduced. Our engineered strains not only laid a foundation for realizing the industrial fermentation of gram-scale ent-kaurene diterpenoids, but also provided a reliable platform for characterization and utilization of kaurene-modifying oxidases, which may generate naturally rare or unnatural ent-kaurenoids with potential bioactivity." @default.
- W4289829536 created "2022-08-05" @default.
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- W4289829536 date "2022-09-01" @default.
- W4289829536 modified "2023-10-03" @default.
- W4289829536 title "De novo production of versatile oxidized kaurene diterpenes in Escherichia coli" @default.
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- W4289829536 doi "https://doi.org/10.1016/j.ymben.2022.08.001" @default.
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