Tropane alkaloid biosynthesis: a centennial review.

Area of Science:

• Biochemistry
• Organic Chemistry
• Plant Science

Background:

• Tropane alkaloids (TAs) are plant secondary metabolites with a nortropane core.
• TAs include hyoscyamine, scopolamine, and cocaine, known for medicinal and toxic properties.
• Understanding TA biosynthesis has been a long-standing challenge since 1901.

Purpose of the Study:

• To review the history of tropane alkaloid biosynthesis research from 1917 to 2020.
• To highlight key discoveries and innovative approaches in TA pathway elucidation.
• To emphasize the significance of biomimetic synthesis in natural product studies.

Main Methods:

• Literature review of studies on tropane alkaloid biosynthesis.
• Analysis of historical and recent research findings.
• Discussion of biomimetic synthesis and total synthesis contributions.

Main Results:

• The complete biosynthetic pathway for hyoscyamine and scopolamine was elucidated by 2020.
• De novo production of these TAs in yeast was achieved.
• Robinson's 1917 biomimetic synthesis of tropinone is recognized as a landmark.

Conclusions:

• Significant progress has been made in understanding plant tropane alkaloid biosynthesis.
• Total synthesis plays a crucial role in validating biosynthetic pathways.
• Recent advancements enable engineered production of valuable TAs.