ベンザスタチン生合成におけるシトクロムP450によるニトレン形成と付加反応を介した5，6員環形成反応

抄録

Biosynthesis of cyclic structures of natural products is important for generating their structural diversity. In some cases, these cyclic structures are responsible for their bioactivities (e.g., a β-lactam ring in β-lactam antibiotics and an aziridine ring in antitumor antibiotics). Therefore, cyclization reaction is among the most important steps in the biosynthesis of natural products. In these steps, chemical reactions important for organic synthesis are often used for synthesizing cyclic structures. For example, the Diels-Alder reaction is used to biosynthesize the decaline structure in mevastatin and lovastatin, which are known for HMG-CoA reductase inhibitors. Another example is the phenol radical coupling reaction, which is used for biosynthesizing the macrocyclic structures of glycopeptide antibiotics. Although cyclic structure biosynthesis has been studied extensively, the biosynthetic pathways of many cyclic structures have not been elucidated. In this review, we focus on benzastatins, the biosynthetic pathway of which our group has analyzed by heterologous expression and in vitro assays using recombinant enzymes. Most importantly, the indoline and tetrahydroquinoline structures of benzastatin derivatives were revealed to be synthesized by an unusual cytochrome P450, BezE. Instead of oxygenation, which most cytochrome P450s catalyze, BezE catalyzes nitrene formation, its addition to a double bond to yield aziridine, and nucleophilic substitution to open the aziridine ring and form a 5- or 6-membered ring.