Biosynthetic consequences of multiple sequential post-transition-state bifurcations.

Area of Science:

• Organic Chemistry
• Computational Chemistry
• Biochemistry

Background:

• Chemical reaction selectivity is typically explained by comparing transition-state structures.
• Predicting product formation in complex molecular architectures is challenging.
• Terpene synthase enzymes biosynthesize complex natural products through intricate reaction pathways.

Purpose of the Study:

• To investigate a novel reaction system where a single transition-state structure yields multiple isomeric products.
• To elucidate the role of post-transition-state dynamics in controlling reaction selectivity.
• To explore the implications for understanding terpene biosynthesis and enzyme evolution.

Main Methods:

• Utilized quasiclassical direct dynamics calculations.
• Employed density functional theory (DFT) to model reaction pathways.
• Analyzed the reaction network connecting a carbocation intermediate to diterpene products and isomers.

Main Results:

• Demonstrated that a single transition-state structure leads to numerous isomers through sequential bifurcations.
• Identified post-transition-state dynamic effects, specifically carbocation vibrational energy distribution, as the key selectivity determinant.
• Revealed complex reaction networks involving cyclizations and rearrangements.

Conclusions:

• Reaction selectivity in complex systems can be governed by dynamics beyond the transition state.
• Findings challenge traditional models of selectivity prediction in organic synthesis.
• Provides new insights into terpene synthase mechanisms and the evolution of natural product biosynthesis.