Biosynthesis of lovastatin analogs with a broadly specific acyltransferase.

Biosynthesis of lovastatin analogs with a broadly specific acyltransferase. Research Abstract Details 

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Biosynthesis of lovastatin analogs with a broadly specific acyltransferase. Abstract Text:

Xinkai Xie,Kenji Watanabe,Wladyslaw A Wojcicki,Clay C C Wang,Yi Tang,

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.

Biosynthesis of lovastatin analogs with a broadly specific acyltransferase. Publishing Authors By Initials

X Xie,K Watanabe,WA Wojcicki,CC Wang,Y Tang,

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: substrate specificity research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: substrate specificity research

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MEDLINE DATE:

Biosynthesis of lovastatin analogs with a broadly specific acyltransferase. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Chemistry & biology

VOLUME: 13

Page Numbers: 1161-9

Journal Abbreviation: Chem. Biol.

ISSN: 1074-5521

DAY: 3

MONTH: Nov

YEAR: 2006

Biosynthesis of lovastatin analogs with a broadly specific acyltransferase. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9500160

Biosynthesis of lovastatin analogs with a broadly specific acyltransferase. Keywords Mesh Terms:

KEYWORDS: Substrate Specificity

MESH TERMS: chemical synthesis

Chemical & Substance for Abstract: Biosynthesis of lovastatin analogs with a broadly specific acyltransferase. Information

Substance Name: Acyltransferases

Registry Number: EC 2.3.-

Grant and Affiliation Information for Biosynthesis of lovastatin analogs with a broadly specific acyltransferase.

AFFILIATION: Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, 5531 Boelter Hall, 420 Westwood Plaza, Los Angeles, California 90095, USA.

Country: England

AGENCY: United States NIGMS

GRANT: R01-GM75857

ACRONYM: GM

MEDLINETA: Chem Biol

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