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Production of N-acetyl cis-4-hydroxy-l-proline by the yeast N-acetyltransferase Mpr1

Paper ID Volume ID Publish Year Pages File Format Full-Text
21161 43209 2012 6 PDF Available
Title
Production of N-acetyl cis-4-hydroxy-l-proline by the yeast N-acetyltransferase Mpr1
Abstract

The proline analog cis-4-hydroxy-l-proline (CHOP), which inhibits the biosynthesis of collagen, has been evaluated as an anticancer, antifibrosis, and antihypertension drug. However, its water solubility and low molecular weight limit its therapeutic potential since it is rapidly excreted. In addition, CHOP is considered to be too toxic due primarily to its systematic effects on noncollagen proteins. To promote retention in blood or decrease toxicity, N-acetylation of CHOP might be a novel approach as a prodrug, instead of other approaches such as the conjugation of poly(ethylene glycol-Lys) or the modification of O-acetylation. In this study, we found that N-acetyltransferase Mpr1 that detoxifies the proline analog azetidine-2-carboxylate in Saccharomyces cerevisiae also converts CHOP into N-acetyl CHOP in vitro and in vivo. Escherichia coli BL21(DE3) cells overexpressing Mpr1 showed greater CHOP resistance than those carrying the vector. To increase the productivity of N-acetyl CHOP, the addition of NaCl into the medium that induces osmotic stress accelerates CHOP uptake into E. coli cells. As a result, the amount of N-acetyl CHOP production in Mpr1-overexpressing cells was 3.5-fold higher than that observed in the cells cultured in the absence of NaCl. The highest yield was achieved during the exponential growth phase of cells in the presence of 2% NaCl (52 μmol N-acetyl CHOP per g wet cell weight). Our results provide a promising approach to microbial production of N-acetyl CHOP as a new prodrug.

Keywords
Yeast; N-Acetyltransferase Mpr1; Proline analog; cis-4-Hydroxy-l-proline; N-Acetyl cis-4-hydroxy-l-proline
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Bioscience and Bioengineering - Volume 114, Issue 2, August 2012, Pages 160–165
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us