A promiscuous proton in taxadiene biosynthesis?

Area of Science:

• Biochemistry
• Quantum Chemistry
• Organic Synthesis

Background:

• Taxa-4,11-diene is a key intermediate in Taxol biosynthesis.
• The biosynthesis pathway involves proton transfer steps.
• Previous models proposed a direct proton transfer mechanism.

Purpose of the Study:

• To investigate the mechanism of taxa-4,11-diene biosynthesis.
• To explore alternative proton transfer pathways.
• To determine the energetic favorability of different pathways.

Main Methods:

• Quantum chemical calculations were employed.
• The study focused on a two-step proton-transfer pathway.
• Analysis of the bicyclic diterpene skeleton and its interaction with a mobile proton.

Main Results:

• A two-step proton-transfer pathway was identified as energetically favorable.
• This pathway interconverts key intermediates in taxa-4,11-diene biosynthesis.
• The bicyclic diterpene skeleton acts as a cage for a mobile proton.

Conclusions:

• The identified two-step pathway is a more energetically favorable alternative to direct proton transfer.
• This finding refines our understanding of Taxol precursor biosynthesis.
• The unique structure of the diterpene skeleton plays a critical role in the reaction mechanism.