Review
Enzyme Mechanisms for Polycyclic Triterpene Formation
K. Ulrich Wendt Dr.,
Georg E. Schulz Prof. Dr.,
Elias J. Corey Prof. Dr.,
David R. Liu Prof. Dr.,
K. Ulrich Wendt Dr.
Institut für Organische Chemie und Biochemie Albertstrasse 21, 79104 Freiburg (Germany) Fax: (+49) 761-203-6161
Search for more papers by this authorGeorg E. Schulz Prof. Dr.
Institut für Organische Chemie und Biochemie Albertstrasse 21, 79104 Freiburg (Germany) Fax: (+49) 761-203-6161
Search for more papers by this authorElias J. Corey Prof. Dr.
Department of Chemistry and Chemical Biology Harvard University 12 Oxford Street, Cambridge, MA 02138 (USA) Fax: (+1) 617-496-5688
Search for more papers by this authorDavid R. Liu Prof. Dr.
Department of Chemistry and Chemical Biology Harvard University 12 Oxford Street, Cambridge, MA 02138 (USA) Fax: (+1) 617-496-5688
Search for more papers by this authorK. Ulrich Wendt Dr.,
Georg E. Schulz Prof. Dr.,
Elias J. Corey Prof. Dr.,
David R. Liu Prof. Dr.,
K. Ulrich Wendt Dr.
Institut für Organische Chemie und Biochemie Albertstrasse 21, 79104 Freiburg (Germany) Fax: (+49) 761-203-6161
Search for more papers by this authorGeorg E. Schulz Prof. Dr.
Institut für Organische Chemie und Biochemie Albertstrasse 21, 79104 Freiburg (Germany) Fax: (+49) 761-203-6161
Search for more papers by this authorElias J. Corey Prof. Dr.
Department of Chemistry and Chemical Biology Harvard University 12 Oxford Street, Cambridge, MA 02138 (USA) Fax: (+1) 617-496-5688
Search for more papers by this authorDavid R. Liu Prof. Dr.
Department of Chemistry and Chemical Biology Harvard University 12 Oxford Street, Cambridge, MA 02138 (USA) Fax: (+1) 617-496-5688
Search for more papers by this authorFirst published: 11 August 2000
Citations: 386
Graphical Abstract
A potent combination of organic synthesis, bioorganic chemistry, site-directed mutagenesis, and structural biology has enhanced our understanding of the mechanisms of enzyme-catalyzed triterpene formation in recent years. The remarkable enzymatic cyclization of squalene or oxidosqualene yields complex polycyclic products, including hopene and the steroid precursor lanosterol (see picture).
Abstract
The mechanisms by which triterpene cyclases transform olefins into complex and biologically important polycyclic products have fueled nearly half a century of intense research. Recent chemical and biological studies, together with previous findings, provide intriguing new insights into the enzymatic mechanism of triterpene formation and form a surprisingly detailed picture of these elegant catalysts. It can be concluded that the role of the oxidosqualene cyclases involves protection of the intermediate carbocation against addition of water or deprotonation by base, thereby allowing the shift of the hydride and methyl groups along a thermodynamically and kinetically favorable cascade. Key questions in the areas of structural biology, site-directed mutagenesis, and directed evolution are apparent, now that the first structure of a triterpene cyclase is known.
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