A potential energy surface bifurcation in terpene biosynthesis.

Area of Science:

• Biochemistry
• Organic Chemistry
• Natural Product Synthesis

Background:

• Terpenes are diverse natural products with complex structures.
• Terpene synthases (cyclases) catalyze carbocation rearrangements to form terpene skeletons.
• Mechanisms of terpene cyclization are partially understood, but factors controlling carbocation intermediates remain unclear.

Purpose of the Study:

• To investigate the factors controlling carbocation intermediate and transition-state structures in terpene biosynthesis.
• To explore the potential for pathway bifurcation after transition states in terpene cyclizations.
• To assess the significance of bifurcating pathways in the natural production of complex terpenes.

Main Methods:

• Computational analysis of terpene cyclase reaction mechanisms.
• Investigating carbocation rearrangement pathways.
• Examining transition-state structures and post-transition-state dynamics.

Main Results:

• Identified specific transition-state structures that can lead to pathway bifurcation.
• Demonstrated that post-transition-state divergence results in terpenes with distinct skeletal architectures.
• Showed that such bifurcating pathways can occur in the biosynthesis of complex terpenes.

Conclusions:

• Pathway bifurcation after transition states is a key mechanism in generating terpene structural diversity.
• This mechanism offers a new perspective on the formation of complex molecular architectures in nature.
• Understanding these bifurcating pathways is crucial for elucidating terpene biosynthesis and engineering novel terpenes.