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A novel d-2-hydroxy acid dehydrogenase with high substrate preference for phenylpyruvate originating from lactic acid bacteria: Structural analysis on the substrate specificity.
Enzyme Microb Technol 2019; 125:37-44EM

Abstract

2-Hydroxy acid dehydrogenases (2-HADHs) have been implicated in the synthesis of 2-hydroxy acids from 2-oxo acids that are used in wide areas of industry. d-lactate dehydrogenases (d-LDHs), a subfamily of 2-HADH, have been utilized to this purpose, yet they exhibited relatively low catalytic activity to the 2-oxo acids with large functional groups at C3. In this report, four putative 2-HADHs from Oenococcus oeni, Weissella confusa, Weissella koreensis and Pediococcus claussenii were examined for activity on phenylpyruvate (PPA), a substrate to 3-phenyllactic acid (PLA) with a C3 phenyl group. The 2-HADH from P. claussenii was found to have the highest kcat/Km on PPA with 1,348.03 s-1 mM-1 among the four enzymes with higher substrate preference for PPA than pyruvate. Sequential, structural and mutational analysis of the enzyme revealed that it belonged to the d-LDH family, and phenylalanine at the position 51 was the key residue for the PPA binding to the active site via hydrophobic interaction, whereas in the 2-HADHs from O. oeni and W. confusa the hydrophilic tyrosine undermined the interaction. Because phenyllactate is a potential precursor for pharmaceutical compounds, antibiotics and biopolymers, the enzyme could increase the efficiency of bio-production of valuable chemicals. This study suggests a structural basis for the high substrate preference of the 2-HADH, and further engineering possibilities to synthesize versatile 2-hydroxy acids.

Authors+Show Affiliations

Program of Bioengineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea. Electronic address: hsl0828@snu.ac.kr.Department of Biochemical Engineering, Gangneung-Wonju National University, 7, Jukheon-gil, Gangneung-si, Gangwon-do, 25457, Republic of Korea. Electronic address: jspark@gwnu.ac.kr.Program of Bioengineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea; School of Chemical and Biological Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea. Electronic address: yjyoo@snu.ac.kr.Department of Biochemical Engineering, Gangneung-Wonju National University, 7, Jukheon-gil, Gangneung-si, Gangwon-do, 25457, Republic of Korea. Electronic address: yjyeon@gwnu.ac.kr.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30885323

Citation

Lee, Hoe-Suk, et al. "A Novel D-2-hydroxy Acid Dehydrogenase With High Substrate Preference for Phenylpyruvate Originating From Lactic Acid Bacteria: Structural Analysis On the Substrate Specificity." Enzyme and Microbial Technology, vol. 125, 2019, pp. 37-44.
Lee HS, Park J, Yoo YJ, et al. A novel d-2-hydroxy acid dehydrogenase with high substrate preference for phenylpyruvate originating from lactic acid bacteria: Structural analysis on the substrate specificity. Enzyme Microb Technol. 2019;125:37-44.
Lee, H. S., Park, J., Yoo, Y. J., & Yeon, Y. J. (2019). A novel d-2-hydroxy acid dehydrogenase with high substrate preference for phenylpyruvate originating from lactic acid bacteria: Structural analysis on the substrate specificity. Enzyme and Microbial Technology, 125, pp. 37-44. doi:10.1016/j.enzmictec.2019.02.008.
Lee HS, et al. A Novel D-2-hydroxy Acid Dehydrogenase With High Substrate Preference for Phenylpyruvate Originating From Lactic Acid Bacteria: Structural Analysis On the Substrate Specificity. Enzyme Microb Technol. 2019;125:37-44. PubMed PMID: 30885323.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel d-2-hydroxy acid dehydrogenase with high substrate preference for phenylpyruvate originating from lactic acid bacteria: Structural analysis on the substrate specificity. AU - Lee,Hoe-Suk, AU - Park,Jisu, AU - Yoo,Young Je, AU - Yeon,Young Joo, Y1 - 2019/02/23/ PY - 2018/12/21/received PY - 2019/02/15/revised PY - 2019/02/22/accepted PY - 2019/3/20/entrez PY - 2019/3/20/pubmed PY - 2019/3/20/medline KW - Phenyllactic acid KW - Structural analysis KW - Substrate specificity KW - d-2-hydroxy acid dehydrogenase SP - 37 EP - 44 JF - Enzyme and microbial technology JO - Enzyme Microb. Technol. VL - 125 N2 - 2-Hydroxy acid dehydrogenases (2-HADHs) have been implicated in the synthesis of 2-hydroxy acids from 2-oxo acids that are used in wide areas of industry. d-lactate dehydrogenases (d-LDHs), a subfamily of 2-HADH, have been utilized to this purpose, yet they exhibited relatively low catalytic activity to the 2-oxo acids with large functional groups at C3. In this report, four putative 2-HADHs from Oenococcus oeni, Weissella confusa, Weissella koreensis and Pediococcus claussenii were examined for activity on phenylpyruvate (PPA), a substrate to 3-phenyllactic acid (PLA) with a C3 phenyl group. The 2-HADH from P. claussenii was found to have the highest kcat/Km on PPA with 1,348.03 s-1 mM-1 among the four enzymes with higher substrate preference for PPA than pyruvate. Sequential, structural and mutational analysis of the enzyme revealed that it belonged to the d-LDH family, and phenylalanine at the position 51 was the key residue for the PPA binding to the active site via hydrophobic interaction, whereas in the 2-HADHs from O. oeni and W. confusa the hydrophilic tyrosine undermined the interaction. Because phenyllactate is a potential precursor for pharmaceutical compounds, antibiotics and biopolymers, the enzyme could increase the efficiency of bio-production of valuable chemicals. This study suggests a structural basis for the high substrate preference of the 2-HADH, and further engineering possibilities to synthesize versatile 2-hydroxy acids. SN - 1879-0909 UR - https://www.unboundmedicine.com/medline/citation/30885323/A_novel_d-2-hydroxy_acid_dehydrogenase_with_high_substrate_preference_for_phenylpyruvate_originating_from_lactic_acid_bacteria:_Structural_analysis_on_the_substrate_specificity L2 - https://linkinghub.elsevier.com/retrieve/pii/S0141-0229(19)30030-4 DB - PRIME DP - Unbound Medicine ER -