(S)-canadine synthase
(S)-canadine synthase is an enzyme that catalyzes the stereospecific synthesis of (S)-canadine from (S)-tetrahydroprotoberberine. It is a key enzyme in the biosynthesis of berberine and related protoberberine alkaloids in plants, particularly those within the Berberidaceae, Papaveraceae, and Ranunculaceae families.
Reaction Catalyzed:
(S)-tetrahydroprotoberberine + O2 + NADPH + H+ ⇌ (S)-canadine + H2O + NADP+
The enzyme utilizes NADPH as a cofactor and requires molecular oxygen for its activity. The reaction involves an oxidative cyclization, introducing a methylenedioxy bridge between two adjacent aromatic carbons on the tetrahydroprotoberberine substrate. The stereochemistry of the product, (S)-canadine, is strictly controlled by the enzyme.
Mechanism:
While the precise mechanism of (S)-canadine synthase is still under investigation, it is believed to involve a flavin-dependent monooxygenase activity. The flavin cofactor, likely FAD or FMN, is reduced by NADPH, and the reduced flavin then reacts with molecular oxygen to form an activated oxygen species. This activated oxygen species then participates in the oxidative cyclization of (S)-tetrahydroprotoberberine to form (S)-canadine.
Biological Significance:
(S)-canadine synthase plays a crucial role in the production of protoberberine alkaloids, which possess a range of pharmacological activities. Berberine, a major protoberberine alkaloid, has been shown to have antimicrobial, anti-inflammatory, and antidiabetic properties. The enzyme's activity directly impacts the levels of these valuable compounds in medicinal plants.
Occurrence and Purification:
(S)-canadine synthase has been identified and characterized in various plant species that produce berberine alkaloids. The enzyme can be extracted from plant tissues and purified using various biochemical techniques, including column chromatography and affinity chromatography. The gene encoding (S)-canadine synthase has been cloned and expressed in heterologous systems, allowing for detailed studies of its structure and function.
Synonyms:
- Tetrahydroprotoberberine synthase
- Berberine bridge enzyme-like protein