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A non-classical biosynthetic route enables tocopherol synthesis in bacteria
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DOI：10.1038/s42255-026-01576-y.png)
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Abstract
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Tocopherols have been widely applied in healthcare, medicine, animal feed and other fields. However, microbial synthesis of tocopherols with industrial potential has not been accomplished yet. Here we report a non-classical biosynthetic route for tocopherol synthesis in Rhodobacter species that bypasses the classical α-tocopherol pathway requiring the 2,3-dimethyl-5-phytyl-1,4-benzoquinone (DMPBQ) as an intermediate. In particular, a Rhodobacter methyltransferase with bifunctional γ/β-tocopherol methyltransferase activities is identified, which can directly synthesize α-tocopherol from δ-tocopherol and γ/β-tocopherols. Furthermore, geranylgeranyl pyrophosphate reductase (GR) plays an important role in reducing tocotrienols into tocopherols. Through systematic metabolic engineering, the engineered Rhodobacter sphaeroides produced a total titer of 508.21 mg l−1 tocopherols in shake flasks, and 3.51 g l−1 under the fed-batch fermentation after process optimization. Taken together, these results offer a non-classical biosynthetic pathway for efficient tocopherol biosynthesis, which would pave the way for future commercial production of tocopherols by microbial fermentation. The study reports a non-classical tocopherol pathway in Rhodobacter that enables heterologous α-tocopherol synthesis by bypassing DMPBQ via a γ/β-tocopherol methyltransferase.
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