Conversion of substrate analogs suggests a Michael cyclization in iridoid biosynthesis

Area of Science:

• Biochemistry
• Organic Chemistry
• Enzymology

Background:

• Iridoid monoterpenes possess a unique core structure formed via a distinct cyclization reaction.
• The enzyme iridoid synthase catalyzes this reaction and is mechanistically different from other terpene cyclases.

Purpose of the Study:

• To investigate the mechanism of iridoid synthase.
• To synthesize substrate analogs for probing enzyme function.

Main Methods:

• Synthesis of two substrate analogs for iridoid synthase.
• Enzymatic assays using these analogs.
• Analysis of the product profile of the native substrate.

Main Results:

• Enzymatic assays and product profile analysis suggest a Michael reaction mechanism for iridoid synthase.
• The findings provide insights into the distinct catalytic strategy of iridoid synthase.

Conclusions:

• Iridoid synthase likely employs a Michael reaction for its unique cyclization process.
• This mechanistic understanding can guide the engineering of iridoid synthase for synthesizing novel cyclic compounds from non-natural substrates.