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Updated: Mar 22, 2026
07:59
A Customizable Approach for the Enzymatic Production and Purification of Diterpenoid Natural Products
Published on: October 4, 2019
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General base-general acid catalysis by terpenoid cyclases.
Travis A Pemberton1, David W Christianson1,2
1Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA, USA.
The Journal of Antibiotics
|April 14, 2016
Summary
Inorganic pyrophosphate, not amino acids, likely enables the complex acid-base chemistry in bacterial terpenoid cyclases. This finding clarifies catalytic mechanisms for these crucial enzymes.
Area of Science:
- Biochemistry
- Enzymology
- Organic Chemistry
Background:
- Terpenoid cyclases perform complex multi-step reactions involving carbocation intermediates.
- Pentalenene synthase, the first bacterial terpenoid cyclase with a crystal structure, produces a precursor to pentalenolactone antibiotics.
- Active sites of these enzymes are typically nonpolar, lacking typical amino acid residues for acid-base catalysis.
Purpose of the Study:
- To investigate the catalytic mechanism of terpenoid cyclases, specifically identifying the species responsible for essential Brønsted acid-base chemistry.
- To explore the role of inorganic pyrophosphate in facilitating these enzymatic reactions.
Main Methods:
- Structural analysis of pentalenene synthase and other terpenoid cyclases.
- Review of biological and nonbiological systems utilizing phosphate derivatives in catalysis.
Main Results:
- Terpenoid cyclase active sites lack typical amino acid side chains for general acid-base catalysis.
- Inorganic pyrophosphate is proposed as the likely catalyst for Brønsted acid-base chemistry in these enzymes.
- Phosphate derivatives exhibit Brønsted acid-base activities comparable to amino acid side chains.
Conclusions:
- Inorganic pyrophosphate plays a crucial role in the catalytic mechanisms of terpenoid cyclases.
- Understanding this mechanism provides insight into the biosynthesis of complex terpenoids and related natural products.
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