Related Experiment Video
Updated: Jul 18, 2026

Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
Published on: November 22, 2014
Biosynthesis of lovastatin analogs with a broadly specific acyltransferase
Xinkai Xie1, Kenji Watanabe, Wladyslaw A Wojcicki
1Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, 5531 Boelter Hall, 420 Westwood Plaza, Los Angeles, California 90095, USA.
Abstract:
The natural product lovastatin and its semisynthetic, more effective derivative, simvastatin, are important drugs for the treatment of hypercholesterolemia. Here, we report the biochemical characterization of a dedicated acyltransferase, LovD, encoded in the lovastatin biosynthetic pathway. We demonstrate that LovD has broad substrate specificity towards the acyl carrier, the acyl substrate, and the decalin acyl acceptor. LovD can efficiently catalyze the acyl transfer from coenzyme A thioesters or N-acetylcysteamine (SNAC) thioesters to monacolin J. When alpha-dimethylbutyryl-SNAC was used as the acyl donor, LovD was able to convert monacolin J and 6-hydroxyl-6-desmethylmonacolin J into simvastatin and huvastatin, respectively. Using the Escherichia coli LovD overexpression strain as a whole-cell biocatalyst, preparative amounts of simvastatin were synthesized in a single fermentation step. Our results demonstrate LovD is an attractive enzyme for engineered biosynthesis of pharmaceutically important cholesterol-lowering drugs.
More Related Videos
Related Concept Videos
Biosynthesis of Lipids
Alkylation of β-Ketoester Enolates: Acetoacetic Ester Synthesis
Carboxylic Acid Derivatives: Overview
Nucleophilic Acyl Substitution of Carboxylic Acid Derivatives
Lipid-Lowering Drugs: Statins and Miscellaneous Agents
Carboxylic Acids to Esters: Acid-Catalyzed (Fischer) Esterification Mechanism

