TY - JOUR
T1 - Properties and biotechnological applications of natural and engineered haloalkane dehalogenases
AU - Nagata, Yuji
AU - Ohtsubo, Yoshiyuki
AU - Tsuda, Masataka
N1 - Funding Information:
This work was partly supported by JSPS KAKENHI grant number 22380047 and 25292043.
Publisher Copyright:
© 2015, Springer-Verlag Berlin Heidelberg.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - Haloalkane dehalogenases (HLDs) convert halogenated compounds to corresponding alcohols, halides, and protons. They belong to α/β-hydrolases, and their principal catalytic mechanism is SN2 nucleophilic substitution followed by the addition of water. Since HLDs generally have broad and different substrate specificities, they have various biotechnological applications. HLDs have previously been believed to be present only in bacterial strains that utilize xenobiotic halogenated compounds, and three archetypal HLDs, i.e., DhlA, DhaA, and LinB, have been intensively investigated by biochemical, structural, and computational analyses. Furthermore, by using the resulting data and target-selected random mutagenesis approaches, these HLDs have been successfully engineered to improve their substrate specificities and activities. In addition, important insights into protein evolution have been obtained by studying these HLDs. At the same time, the genome and metagenome information has revealed that HLD homologues are widely distributed in many bacterial strains, including ones that have not been reported to degrade halogenated compounds. Some of these cryptic HLD homologues have been experimentally confirmed to be “true” HLDs with unique substrate specificities and enantioselectivities. Although their biological functions and physiological roles remain mysterious, these potential HLDs are considered promising materials for the development of new biocatalysts.
AB - Haloalkane dehalogenases (HLDs) convert halogenated compounds to corresponding alcohols, halides, and protons. They belong to α/β-hydrolases, and their principal catalytic mechanism is SN2 nucleophilic substitution followed by the addition of water. Since HLDs generally have broad and different substrate specificities, they have various biotechnological applications. HLDs have previously been believed to be present only in bacterial strains that utilize xenobiotic halogenated compounds, and three archetypal HLDs, i.e., DhlA, DhaA, and LinB, have been intensively investigated by biochemical, structural, and computational analyses. Furthermore, by using the resulting data and target-selected random mutagenesis approaches, these HLDs have been successfully engineered to improve their substrate specificities and activities. In addition, important insights into protein evolution have been obtained by studying these HLDs. At the same time, the genome and metagenome information has revealed that HLD homologues are widely distributed in many bacterial strains, including ones that have not been reported to degrade halogenated compounds. Some of these cryptic HLD homologues have been experimentally confirmed to be “true” HLDs with unique substrate specificities and enantioselectivities. Although their biological functions and physiological roles remain mysterious, these potential HLDs are considered promising materials for the development of new biocatalysts.
KW - Bacterial genome
KW - Environmental pollutant
KW - Haloalkane dehalogenase
KW - Halogenated compound
KW - Hydrolase
KW - Protein engineering
KW - Protein evolution
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U2 - 10.1007/s00253-015-6954-x
DO - 10.1007/s00253-015-6954-x
M3 - Review article
C2 - 26373728
AN - SCOPUS:84947035077
VL - 99
SP - 9865
EP - 9881
JO - Applied Microbiology and Biotechnology
JF - Applied Microbiology and Biotechnology
SN - 0175-7598
IS - 23
ER -