Efficient production of (R)-2-hydroxy-4-phenylbutyric acid by using a coupled reconstructed D-lactate dehydrogenase and formate dehydrogenase system.

<h4>Background</h4>(R)-2-hydroxy-4-phenylbutyric acid [(R)-HPBA] is a key precursor for the production of angiotensin-converting enzyme inhibitors. However, the product yield and concentration of reported (R)-HPBA synthetic processes remain unsatisfactory.<h4>Methodology/principal...

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Autores principales: Binbin Sheng, Zhaojuan Zheng, Min Lv, Haiwei Zhang, Tong Qin, Chao Gao, Cuiqing Ma, Ping Xu
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Publicado: Public Library of Science (PLoS) 2014
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spelling oai:doaj.org-article:00b317fe30014897a1d56ffeb366580b2021-11-25T06:06:04ZEfficient production of (R)-2-hydroxy-4-phenylbutyric acid by using a coupled reconstructed D-lactate dehydrogenase and formate dehydrogenase system.1932-620310.1371/journal.pone.0104204https://doaj.org/article/00b317fe30014897a1d56ffeb366580b2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25089519/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>(R)-2-hydroxy-4-phenylbutyric acid [(R)-HPBA] is a key precursor for the production of angiotensin-converting enzyme inhibitors. However, the product yield and concentration of reported (R)-HPBA synthetic processes remain unsatisfactory.<h4>Methodology/principal findings</h4>The Y52L/F299Y mutant of NAD-dependent D-lactate dehydrogenase (D-nLDH) in Lactobacillus bulgaricus ATCC 11842 was found to have high bio-reduction activity toward 2-oxo-4-phenylbutyric acid (OPBA). The mutant D-nLDHY52L/F299Y was then coexpressed with formate dehydrogenase in Escherichia coli BL21 (DE3) to construct a novel biocatalyst E. coli DF. Thus, a novel bio-reduction process utilizing whole cells of E. coli DF as the biocatalyst and formate as the co-substrate for cofactor regeneration was developed for the production of (R)-HPBA from OPBA. The biocatalysis conditions were then optimized.<h4>Conclusions/significance</h4>Under the optimum conditions, 73.4 mM OPBA was reduced to 71.8 mM (R)-HPBA in 90 min. Given its high product enantiomeric excess (>99%) and productivity (47.9 mM h(-1)), the constructed coupling biocatalysis system is a promising alternative for (R)-HPBA production.Binbin ShengZhaojuan ZhengMin LvHaiwei ZhangTong QinChao GaoCuiqing MaPing XuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e104204 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Binbin Sheng
Zhaojuan Zheng
Min Lv
Haiwei Zhang
Tong Qin
Chao Gao
Cuiqing Ma
Ping Xu
Efficient production of (R)-2-hydroxy-4-phenylbutyric acid by using a coupled reconstructed D-lactate dehydrogenase and formate dehydrogenase system.
description <h4>Background</h4>(R)-2-hydroxy-4-phenylbutyric acid [(R)-HPBA] is a key precursor for the production of angiotensin-converting enzyme inhibitors. However, the product yield and concentration of reported (R)-HPBA synthetic processes remain unsatisfactory.<h4>Methodology/principal findings</h4>The Y52L/F299Y mutant of NAD-dependent D-lactate dehydrogenase (D-nLDH) in Lactobacillus bulgaricus ATCC 11842 was found to have high bio-reduction activity toward 2-oxo-4-phenylbutyric acid (OPBA). The mutant D-nLDHY52L/F299Y was then coexpressed with formate dehydrogenase in Escherichia coli BL21 (DE3) to construct a novel biocatalyst E. coli DF. Thus, a novel bio-reduction process utilizing whole cells of E. coli DF as the biocatalyst and formate as the co-substrate for cofactor regeneration was developed for the production of (R)-HPBA from OPBA. The biocatalysis conditions were then optimized.<h4>Conclusions/significance</h4>Under the optimum conditions, 73.4 mM OPBA was reduced to 71.8 mM (R)-HPBA in 90 min. Given its high product enantiomeric excess (>99%) and productivity (47.9 mM h(-1)), the constructed coupling biocatalysis system is a promising alternative for (R)-HPBA production.
format article
author Binbin Sheng
Zhaojuan Zheng
Min Lv
Haiwei Zhang
Tong Qin
Chao Gao
Cuiqing Ma
Ping Xu
author_facet Binbin Sheng
Zhaojuan Zheng
Min Lv
Haiwei Zhang
Tong Qin
Chao Gao
Cuiqing Ma
Ping Xu
author_sort Binbin Sheng
title Efficient production of (R)-2-hydroxy-4-phenylbutyric acid by using a coupled reconstructed D-lactate dehydrogenase and formate dehydrogenase system.
title_short Efficient production of (R)-2-hydroxy-4-phenylbutyric acid by using a coupled reconstructed D-lactate dehydrogenase and formate dehydrogenase system.
title_full Efficient production of (R)-2-hydroxy-4-phenylbutyric acid by using a coupled reconstructed D-lactate dehydrogenase and formate dehydrogenase system.
title_fullStr Efficient production of (R)-2-hydroxy-4-phenylbutyric acid by using a coupled reconstructed D-lactate dehydrogenase and formate dehydrogenase system.
title_full_unstemmed Efficient production of (R)-2-hydroxy-4-phenylbutyric acid by using a coupled reconstructed D-lactate dehydrogenase and formate dehydrogenase system.
title_sort efficient production of (r)-2-hydroxy-4-phenylbutyric acid by using a coupled reconstructed d-lactate dehydrogenase and formate dehydrogenase system.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/00b317fe30014897a1d56ffeb366580b
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