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

Journal of Bioscience and Bioengineering
Bach Thi Mai HoaHiroshi Takagi

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 cult...Continue Reading

References

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Sep 15, 2009·Yeast·Kaoru Ogawa-MitsuhashiKappei Tsukahara

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Citations

Jun 20, 2013·Applied Microbiology and Biotechnology·Thi Mai Hoa Bach, Hiroshi Takagi
Jul 3, 2013·Proceedings of the National Academy of Sciences of the United States of America·Ryo NasunoHiroshi Takagi
Apr 16, 2020·Applied Microbiology and Biotechnology·Ryotaro Hara, Kuniki Kino
Apr 10, 2019·Journal of Industrial Microbiology & Biotechnology·Masataka OhashiHiroshi Takagi
Apr 23, 2021·Microbial Cell Factories·Zhenyu ZhangXiaohe Chu

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