title: Efficient production of (R)-2-hydroxy-4-phenylbutyric acid by using a coupled reconstructed D-lactate dehydrogenase and formate dehydrogenase system.
abstract: BACKGROUND
  (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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: State Key Laboratory of Microbial Technology, Shandong University, Jinan, People's Republic of China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Sheng
authors.affiliation: College of Chemical Engineering, Nanjing Forestry University, Nanjing, People's Republic of China.
authors.forename: Zhaojuan
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Microbial Technology, Shandong University, Jinan, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Lv
authors.affiliation: State Key Laboratory of Microbial Technology, Shandong University, Jinan, People's Republic of China.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Microbial Technology, Shandong University, Jinan, People's Republic of China.
authors.forename: Tong
authors.initials: T
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Microbial Technology, Shandong University, Jinan, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Microbial Technology, Shandong University, Jinan, People's Republic of China.
authors.forename: Cuiqing
authors.initials: C
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Microbial Technology, Shandong University, Jinan, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000737:chemistry / Q000235:genetics / Q000254:growth & development; D005285:Fermentation; D005560:Formate Dehydrogenases / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D045022:Lactate Dehydrogenases / Q000235:genetics* / Q000378:metabolism; D007778:Lactobacillus / Q000201:enzymology; D009154:Mutation; D010654:Phenylbutyrates / Q000138:chemical synthesis / Q000378:metabolism; D015202:Protein Engineering
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D010654:Phenylbutyrates; C078196:2-hydroxy-4-phenylbutyric acid; D045022:Lactate Dehydrogenases; C071195:D-lactate dehydrogenase; D005560:Formate Dehydrogenases
references.citation: Biotechnol Lett. 2014 Mar;36(3):627-31
references.pmid: 24249102
references.citation: Org Biomol Chem. 2011 Oct 26;9(22):7941-50
references.pmid: 21989535
references.citation: Anal Biochem. 1978 Jun 15;87(1):206-10
references.pmid: 98070
references.citation: Biotechnol Prog. 2005 Mar-Apr;21(2):366-71
references.pmid: 15801772
references.citation: J Biotechnol. 2013 Dec;168(4):493-8
references.pmid: 24120725
references.citation: Chem Commun (Camb). 2010 Apr 28;46(16):2754-6
references.pmid: 20369172
references.citation: J Biotechnol. 1992 Jul;24(3):315-27
references.pmid: 1368898
references.citation: Bioresour Technol. 2013 Jun;137:111-5
references.pmid: 23587814
references.citation: Sci Rep. 2013 Dec 02;3:3401
references.pmid: 24292439
references.citation: Bioresour Technol. 2013 Oct;146:736-739
references.pmid: 23932744
references.citation: Sci Rep. 2013;3:2643
references.pmid: 24025762
references.citation: Biotechnol Bioeng. 2005 Oct 20;92(2):137-46
references.pmid: 16037987
references.citation: PLoS One. 2011 Apr 20;6(4):e19030
references.pmid: 21533054
references.citation: Org Lett. 2012 Apr 20;14(8):1982-5
references.pmid: 22480179
references.citation: Eur J Biochem. 1976 Feb 2;62(1):151-60
references.pmid: 1248477
references.citation: Appl Environ Microbiol. 2012 May;78(9):3480-3
references.pmid: 22344644