A non-classical biosynthetic route enables tocopherol synthesis in bacteria

Area of Science:

• Microbial biosynthesis
• Synthetic biology
• Biotechnology

Background:

• Tocopherols are vital compounds used in healthcare and animal feed.
• Current microbial synthesis methods for tocopherols lack industrial viability.
• Existing pathways rely on specific intermediates like 2,3-dimethyl-5-phytyl-1,4-benzoquinone (DMPBQ).

Purpose of the Study:

• To establish an industrially feasible microbial tocopherol biosynthesis route.
• To engineer Rhodobacter species for efficient tocopherol production.
• To explore a non-classical biosynthetic pathway for tocopherols.

Main Methods:

• Identification of a novel Rhodobacter methyltransferase with bifunctional activity.
• Metabolic engineering of Rhodobacter sphaeroides.
• Utilizing geranylgeranyl pyrophosphate reductase (GR) to convert tocotrienols to tocopherols.

Main Results:

• A non-classical pathway bypassing DMPBQ was established.
• Engineered Rhodobacter sphaeroides produced 508.21 mg l⁻¹ tocopherols in shake flasks.
• A fed-batch fermentation yielded 3.51 g l⁻¹ tocopherols after optimization.

Conclusions:

• A novel, efficient non-classical pathway for tocopherol biosynthesis was developed.
• This research enables potential commercial production of tocopherols via microbial fermentation.
• The findings offer a significant advancement in biotechnological production of tocopherols.