Stereoselective hydrolysis of aryl-substituted dihydropyrimidines by hydantoinases

被引:12
作者
Engel, U. [1 ]
Syldatk, C. [1 ]
Rudat, J. [1 ]
机构
[1] KIT, Inst Proc Engn Life Sci, Sect Tech Biol 2, D-76131 Karlsruhe, Germany
关键词
Beta-amino acid; Hydantoinase; Dihydropyrimidinase; Carbamoylase; BETA-AMINO ACIDS; 5-SUBSTITUTED HYDANTOINS; ESCHERICHIA-COLI; PSEUDOMONAS SP; CINNAMIC ACID; AMIDOHYDROLASE; GENES; PURIFICATION; PEPTIDES; ENZYME;
D O I
10.1007/s00253-011-3691-7
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
In this study, we investigated the possibility of using a modified hydantoinase process for the production of optically pure beta-amino acids. Two aryl-substituted dihydropyrimidines -6-phenyl-5,6-dihydrouracil (PheDU) and -chloro--6-phenyl-5,6-dihydrouracil (ClPheDU) were synthesized. Hydrolysis of these novel substrates to the corresponding -carbamoyl-beta-amino acids by three recombinant -hydantoinases and several bacterial strains was tested. All applied recombinant -hydantoinases and eight bacterial isolates catalyzed the conversion of PheDU to -carbamoyl-beta-phenylalanine (C beta Phe). Some of these biocatalysts showed an enantioselectivity for either the - or the -PheDU enantiomer. The second dihydropyrimidinase substrate ClPheDU was hydrolyzed by all three recombinant -hydantoinases and six of the wild-type strains. To our knowledge, this is the first dihydropyrimidinase activity reported with this aryl-substituted dihydropyrimidine. For selected biocatalysts, hydantoinase activity towards aryl-substituted hydantoins was demonstrated as well. However, none of the bacterial strains tested so far exhibited any carbamoylase activity towards C beta Phe.
引用
收藏
页码:1221 / 1231
页数:11
相关论文
共 43 条
[1]   Enzymatic activity assay of D-hydantoinase by isothermal titration calorimetry.: Determination of the thermodynamic activation parameters for the hydrolysis of several substrates [J].
Andújar-Sánchez, M ;
Las Heras-Vázquez, FJ ;
Clemente-Jiménez, JM ;
Martínez-Rodríguez, S ;
Camara-Artigas, A ;
Rodríguez-Vico, F ;
Jara-Pérez, V .
JOURNAL OF BIOCHEMICAL AND BIOPHYSICAL METHODS, 2006, 67 (01) :57-66
[2]   GenBank [J].
Benson, Dennis A. ;
Karsch-Mizrachi, Ilene ;
Lipman, David J. ;
Ostell, James ;
Wheeler, David L. .
NUCLEIC ACIDS RESEARCH, 2006, 34 :D16-D20
[4]   Isolation and molecular characterization of a novel D-hydantoinase from Jannaschia sp CCS1 [J].
Cai, Yuanheng ;
Trodler, Peter ;
Jiang, Shimin ;
Zhang, Weiwen ;
Wu, Yan ;
Lu, Yinhua ;
Yang, Sheng ;
Jiang, Weihong .
FEBS JOURNAL, 2009, 276 (13) :3575-3588
[5]   β-peptides:: From structure to function [J].
Cheng, RP ;
Gellman, SH ;
DeGrado, WF .
CHEMICAL REVIEWS, 2001, 101 (10) :3219-3232
[6]  
Dakin HD, 1914, J BIOL CHEM, V17, P29
[7]   Genes responsible for hydantoin degradation of a halophilic Ochrobactrum sp G21 and Delftia sp 124 -: New insight into relation of D-hydantoinases and dihydropyrimidinases [J].
Duerr, R. ;
Neumann, A. ;
Vielhauer, O. ;
Altenbuchner, J. ;
Burton, S. G. ;
Cowan, D. A. ;
Syldatk, C. .
JOURNAL OF MOLECULAR CATALYSIS B-ENZYMATIC, 2008, 52-53 :2-12
[8]   Distribution of hydantoinase activity in bacterial isolates from geographically distinct environmental sources [J].
Dürr, R ;
Vielhauer, O ;
Burton, SG ;
Cowan, DA ;
Puñal, A ;
Brandao, PFB ;
Bull, AT ;
Syldatk, C .
JOURNAL OF MOLECULAR CATALYSIS B-ENZYMATIC, 2006, 39 (1-4) :160-165
[9]  
Durr R, 2007, THESIS U KARLSRUHE T
[10]   Synthesis of uracil, thymine and phenyluracil. [J].
Fischer, E ;
Roeder, G .
BERICHTE DER DEUTSCHEN CHEMISCHEN GESELLSCHAFT, 1901, 34 :3751-3763