De novo progesterone synthesis in plants

The essential roles of progesterone and other C21 steroids in animals are well-documented. Progesterone is an essential hormone for females to maintain a regular menstrual cycle and pregnancy, while also exhibiting anti-inflammatory and antitumor effects. While the biosynthesis pathway of C21 steroids is comprehensively understood in animals, the synthesis mechanisms of progesterone in plants remain unclear. To our best knowledge, this is the first study to elucidate the complete pathway for progesterone biosynthesis in the plant Marsdenia tenacissima, involving the two sterol side chain cleaving cytochrome P450 enzymes (P450scc) Mt108 or Mt150, as well as the {Delta}5-3{beta}-hydroxysteroid dehydrogenase/{Delta}5-{Delta}4 ketosteroid isomerase MtHSD5. This critical discovery paves the way for the sustainable synthesis of steroid hormone drugs using either plants or microbial host cells.