Biosynthesis of Lovastatin Analogs With a Broadly Specific Acyltransferase

Chem Biol. 2006 Nov;13(11):1161-9. doi: 10.1016/j.chembiol.2006.09.008.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl Coenzyme A / chemistry
  • Acyl Coenzyme A / metabolism
  • Acyltransferases / genetics
  • Acyltransferases / metabolism*
  • Anticholesteremic Agents*
  • Aspergillus / genetics
  • Catalysis
  • Escherichia coli / metabolism
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Lovastatin / analogs & derivatives
  • Lovastatin / biosynthesis*
  • Mutation
  • Simvastatin / chemical synthesis
  • Substrate Specificity


  • Acyl Coenzyme A
  • Anticholesteremic Agents
  • Fungal Proteins
  • butyryl-coenzyme A
  • Lovastatin
  • Simvastatin
  • Acyltransferases