Enzymatic synthesis of cyclic triterpenes

Area of Science:

• Biochemistry
• Enzymology
• Organic Chemistry

Background:

• Squalene and oxidosqualene cyclizations are key steps in synthesizing sterols and triterpenes.
• These enzymatic reactions convert polyenes into diverse polycyclic triterpenes.

Purpose of the Study:

• To review recent progress in the chemistry and enzymology of squalene cyclase and oxidosqualene cyclase.
• To highlight structural insights into enzyme-templated cyclization mechanisms.

Main Methods:

• Review of recent crystallographic and structure-based mutagenesis studies.
• Utilization of chemically synthesized active-site probes.
• Analysis of enzyme systems with minor active-site modifications.

Main Results:

• Detailed structural information on enzyme-templated cyclization reactions is emerging.
• Understanding of how subtle active-site changes lead to diverse triterpene products.

Conclusions:

• Recent structural and chemical studies are advancing the understanding of squalene and oxidosqualene cyclases.
• These enzymes play a critical role in the biosynthesis of essential natural products.