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...
Guardado en:
Autores principales: | , , , , , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
Public Library of Science (PLoS)
2014
|
Materias: | |
Acceso en línea: | https://doaj.org/article/00b317fe30014897a1d56ffeb366580b |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:00b317fe30014897a1d56ffeb366580b |
---|---|
record_format |
dspace |
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 |
work_keys_str_mv |
AT binbinsheng efficientproductionofr2hydroxy4phenylbutyricacidbyusingacoupledreconstructeddlactatedehydrogenaseandformatedehydrogenasesystem AT zhaojuanzheng efficientproductionofr2hydroxy4phenylbutyricacidbyusingacoupledreconstructeddlactatedehydrogenaseandformatedehydrogenasesystem AT minlv efficientproductionofr2hydroxy4phenylbutyricacidbyusingacoupledreconstructeddlactatedehydrogenaseandformatedehydrogenasesystem AT haiweizhang efficientproductionofr2hydroxy4phenylbutyricacidbyusingacoupledreconstructeddlactatedehydrogenaseandformatedehydrogenasesystem AT tongqin efficientproductionofr2hydroxy4phenylbutyricacidbyusingacoupledreconstructeddlactatedehydrogenaseandformatedehydrogenasesystem AT chaogao efficientproductionofr2hydroxy4phenylbutyricacidbyusingacoupledreconstructeddlactatedehydrogenaseandformatedehydrogenasesystem AT cuiqingma efficientproductionofr2hydroxy4phenylbutyricacidbyusingacoupledreconstructeddlactatedehydrogenaseandformatedehydrogenasesystem AT pingxu efficientproductionofr2hydroxy4phenylbutyricacidbyusingacoupledreconstructeddlactatedehydrogenaseandformatedehydrogenasesystem |
_version_ |
1718414143063588864 |