Biosyntheses of azetidine-containing natural products

Azetidine is a four-membered polar heterocycle including a basic secondary amine, and is characterized by its high ring-strain energy, strong molecular rigidity and satisfactory stability. As a result, azetidine exhibits great challenges in its chemical synthesis and biosynthesis, which may explain the limited number of azetidine-containing natural products uncovered to date. In particular, the biosynthetic mechanisms of naturally occurring azetidines are poorly understood. Only some of them have been intensively investigated and few reviews have been published for the summarization of azetidine biosynthesis. In this review, we provide a comprehensive description of the biosyntheses of all the azetidine-containing natural products, especially the biosyntheses of azetidine moieties. We hope that this review will draw much attention to the biosynthetic research of the largely unexplored azetidine moieties as well as the discovery of novel azetidine-containing natural products in the near future. This review aims to provide an overview of the biosyntheses of the striking azetidine-containing natural products, with an emphasis on the biosynthetic mechanisms of naturally occurring azetidines.